gebhart/patrepeval huggingface dataset:
Recombinant aequorin and recombinant semi-synthetic aequorins. Cellular Ca2+ ion indicators (1990)

Properties of a recombinant aequorin were investigated in comparison with those of natural aequorin. In chromatographic behaviour the recombinant aequorin did not match any of ten isoaequorins tested, although it was very similar to aequorin J. Its sensitivity to Ca2+ was found to be higher than that of any isoaequorin except aequorin D. The recombinant aequorin exhibited no toxicity when tested in various kinds of cells, even where samples of natural aequorin had been found to be toxic. Properties of four recombinant semi-synthetic aequorins (fch-, hcp-, e- and n-types), prepared from the recombinant apo-aequorin and synthetic analogues of coelenterazine, were approximately parallel with those of corresponding semi-synthetic aequorins prepared from natural apo-aequorin. Both recombinant e-aequorin and natural e-aequorin J luminesced with high values of the luminescence intensity ratio I400/I465, although the ratios were not pCa-dependent. The recombinant aequorin and recombinant semi-synthetic aequorins are highly suited for monitoring cellular Ca2+.
Profiling Antibodies to Mycobacterium tuberculosis by Multiplex Microbead Suspension Arrays for Serodiagnosis of Tuberculosis (2007)

Tuberculosis (TB) is a serious global disease. The fatality rate attributed to TB is among the highest of infectious diseases, with approximately 2 million deaths occurring per year worldwide. Identification of individuals infected with Mycobacterium tuberculosis and screening of their immediate contacts is crucial for controlling the spread of TB. Current methods for detection of M. tuberculosis infection are not efficient, in particular, for testing large numbers of samples. We report a novel and efficient multiplex microbead immunoassay (MMIA), based on Luminex technology, for profiling antibodies to M. tuberculosis. Microbead sets identifiable by unique fluorescence were individually coated with each of several M. tuberculosis antigens and tested in multiplex format for antibody detection in the experimental nonhuman primate model of TB. Certain M. tuberculosis antigens, e.g., ESAT-6, CFP-10, and HspX, were included to enhance the specificity of the MMIA, because these antigens are absent in nontuberculous mycobacteria and the vaccine strain Mycobacterium bovis bacillus Calmette-Guérin. The MMIA enabled simultaneous detection of multiple M. tuberculosis plasma antibodies in several cohorts of macaques representing different stages of infection and/or disease. Antibody profiles were defined in early and latent/chronic infection. These proof-of-concept findings demonstrate the potential clinical use of the MMIA. In addition, the MMIA serodetection system has a potential for mining M. tuberculosis open reading frames (about 4,000) to discover novel target proteins for the development of more-comprehensive TB serodiagnostic tests.
Mini-chromosomes derived from the human Y chromosome by telomere directed chromosome breakage. (1996)

We have used telomeric DNA to break two acrocentric derivatives of the human Y chromosome into mini-chromosomes that are small enough to be size- fractionated by pulsed-field gel electrophoresis. One of the mini-chromosomes is about 7 Mb in size and sequence-tagged site analysis of this molecule suggests that it corresponds to a simple truncation of the short arm of the Y chromosome. Five of the mini-chromosomes are derived from the long arm, are all rearranged by more than a simple truncation, and range in size from 4.0 Mb to 9 Mb. We have studied the mitotic stabilities of these mini-chromosomes and shown that they are stably maintained by cells proliferating in culture for about 100 cell divisions.
Diffusion in silver fluoride (1980)

Diffusion in AgF has been studied with electrical conductivity \ensuremath{\sigma} and $^{19}\mathrm{F}$ relaxation ${T}_{1\ensuremath{\rho}}$ in the rotating frame. We conclude that \ensuremath{\sigma} is given by ${\mathrm{Ag}}^{+}$ diffusion as in other silver halides, while the much slower ${\mathrm{F}}^{\ensuremath{-}}$ diffusion is found from ${T}_{1\ensuremath{\rho}}$.
Adventure Travel and Type 1 Diabetes (2005)

Acute mountain sickness (AMS) occurs unpredictably, consequent to a recent in
X4 Human Immunodeficiency Virus Type 1 gp120 Down-Modulates Expression and Immunogenicity of Codelivered Antigens (2009)

In order to increase the immune breadth of human immunodeficiency virus (HIV) vaccines, strategies such as immunization with several HIV antigens or centralized immunogens have been examined. HIV-1 gp120 protein is a major immunogen of HIV and has been routinely considered for inclusion in both present and future AIDS vaccines. However, recent studies proposed that gp120 interferes with the generation of immune response to codelivered antigens. Here, we investigate whether coimmunization with plasmid-encoded gp120 alters the immune response to other coadministered plasmid encoded antigens such as luciferase or ovalbumin in a mouse model. We found that the presence of gp120 leads to a significant reduction in the expression level of the codelivered antigen in vivo. Antigen presentation by antigen-presenting cells was also reduced and resulted in the induction of weak antigen-specific cellular and humoral immune responses. Importantly, gp120-mediated immune interference was observed after administration of the plasmids at the same or at distinct locations. To characterize the region in gp120 mediating these effects, we used plasmid constructs encoding gp120 that lacks the V1V2 loops (DeltaV1V2) or the V3 loop (DeltaV3). After immunization, the DeltaV1V2, but not the DeltaV3 construct, was able to reduce antigen expression, antigen presentation, and subsequently the immunogenicity of the codelivered antigen. The V3 loop dependence of this phenomenon seems to be limited to V3 loops known to interact with the CXCR4 molecule but not with CCR5. Our study presents a novel mechanism by which HIV-1 gp120 interferes with the immune response against coadministered antigen in a polyvalent vaccine preparation.
Percutaneous tissue ablation by radiofrequency thermal energy as a prelim to tumour ablation (1993)

Porcine hepatic tissue was ablated in vitro and in vivo with radiofrequency (RF) energy applied through various percutaneous probes. Ultrasound was used for guidance. The technique was assessed for potential use to ablate tumours percutaneously. Tissue ablation was performed in two porcine cadaver and six live piglet livers in various experiments, three RF generators with either bipolar gold probes, 18–22 gauge modified angiocath needles, titanium curved and spiral 0.018″ guidewires, three-pronged grabber baskets, and/or a thermistor (temperature-controlled) probe were used to induce the RF effect with simultaneous assessment by real-time ultrasound. Gross and microscopic analysis of the liver was undertaken after acute sacrifice of the animals. The hepatic tissue that surrounded the probe after RF energy application became increasingly echogenic sonographically. The size of the echogenic area on ultrasound corresponded to the size of the thermal lesion on gross and microscopic examination. Thermal lesions up to 2 cm were created. The size of the thermal lesion was proportional to the surface area of the probe, the shape of the probe, the generator power, and the length of time that the RF energy was applied. The thermistor probe permitted improved contact and control by preventing central charring, cavitation, and boiling of the tissue that occasionally was observed with other probes. Percutaneously applied radiofrequency energy using US-guidance and monitoring is a feasible method to ablate hepatic tissue.
Intracellular Ca2+ thresholds that determine survival or death of energy-deprived cells. (1998)

Increase of intracellular ionized or free Ca2+ is thought to play a central role in cell death due to ATP depletion. However, concurrently operative mechanisms of injury that do not require intracellular Ca2+ increases have made it difficult to test this hypothesis or to determine the concentrations at which intracellular Ca2+ becomes lethal. The predominant Ca2+-independent mechanism of injury during ATP depletion involves the loss of cellular glycine. This type of damage can be fully inhibited by adding the amino acid exogenously. Using glycine to suppress Ca2+-independent plasma membrane damage, we have examined the effect of intracellular Ca2+ elevations on cell viability during ATP depletion. Madin-Darby canine kidney (MDCK) cells were depleted of ATP by incubation with a mitochondrial uncoupler in glucose-free medium. Free Ca2+ concentration in the medium was varied between 26 nmol/L and 1.25 mmol/L in the presence of a Ca2+ ionophore. Measurements with the Ca2+ probes fura-2, furaptra, and fura-2FF showed that intracellular Ca2+ was clamped at extracellular levels under these conditions. Cell survival during ATP depletion was indicated by viable cells recovered 24 hours later. The results show that ATP-depleted cells can sustain high levels of intracellular Ca2+ (100 micromol/L) for prolonged periods and remain viable if plasma membrane damage is prevented by glycine. Cell death was observed only when intracellular free Ca2+ was allowed to increase beyond 100 micromol/L, and this was associated with dramatic nuclear alterations: chromatin condensation, loss of nuclear lamins, and breakdown of DNA into large 50- to 150-kb fragments. Our studies demonstrate unexpectedly high resistance of cells to calcium cytotoxicity if glycine that is lost during ATP depletion is restored. In addition, they provide insights into novel mechanisms of nuclear disintegration and DNA damage that are triggered when the high thresholds of intracellular Ca2+ required for cell death are exceeded.
Steroid Receptor Coactivator-1 Coactivates Activating Protein-1-mediated Transactivations through Interaction with the c-Jun and c-Fos Subunits (1998)

Steroid receptor coactivator-1 (SRC-1) specifically bound to the transcription factor AP-1 subunits c-Jun and c-Fos, as demonstrated by the yeast two-hybrid tests and glutathione S-transferase pull down assays. The c-Jun and c-Fos binding sites were localized to the C-terminal subregion of SRC-1 (amino acids 1101-1441) that encompasses the previously described histone acetyltransferase and receptor-binding domains. In mammalian cells, SRC-1, similar to the previous results with CBP-p300 (Arias, J., Alberts, A. S., Brindle, P., Claret, F. X., Smeal, T., Karin, M., Feramisco, J., and Montminy, M. (1994) Nature 370, 226-229; Bannister, A. J., and Kouzarides, T. (1995) EMBO J. 14, 4758-4762), potentiated the AP-1-mediated transactivations in a dose-dependent manner and derepressed the mutual inhibitions between nuclear receptors and AP-1. Furthermore, coexpression of p300 further enhanced this SRC-1-potentiated level of transactivations. Thus, we concluded that at least two distinct coactivator molecules may cooperate to regulate AP-1-dependent transactivations and mediate transrepression between AP-1 and nuclear receptors in vivo.
ChemInform Abstract: KETENE DITHIOACETALS. PART 11. REACTION OF 3‐CYANO‐4‐METHYLTHIO‐2(1H)‐PYRIDONES WITH HYDRAZINE AND GUANIDINE: SYNTHESIS OF NOVEL SUBSTITUTED AND FUSED PYRAZOLO(4,3‐C)PYRIDONE AND PYRIDO(4,3‐D)PYRIMIDINE DERIVATIVES (1978)

Abstract Alkylierung der Pyridone (I) mit Me,SO4 liefert Gemische aus den Derivaten (II) und (III), von denen (IIb) und (IIIb) nicht getrennt werden konnten; eine nahezu quantitative Umwandlung von (III) in (II) erfolgt, wenn man das Gemisch aus (II) und (III) mit MeI erhitzt.
How to stop under-utilization and love multicores (2015)

Hardware trends oblige software to overcome three major challenges against systems scalability: (1) taking advantage of the implicit/vertical parallelism within a core that is enabled through the aggressive micro-architectural features, (2) exploiting the explicit/horizontal parallelism provided by multicores, and (3) achieving predictively efficient execution despite the variability in communication latencies among cores on multisocket multicores. In this three hour tutorial, we shed light on the above three challenges and survey recent proposals to alleviate them. The first part of the tutorial describes the instruction- and data-level parallelism opportunities in a core coming from the hardware and software side. In addition, it examines the sources of under-utilization in a modern processor and presents insights and hardware/software techniques to better exploit the micro-architectural resources of a processor by improving cache locality at the right level of the memory hierarchy. The second part focuses on the scalability bottlenecks of database applications at the level of multicore and multisocket multicore architectures. It first presents a systematic way of eliminating such bottlenecks in online transaction processing workloads, which is based on minimizing unbounded communication, and shows several techniques that minimize bottlenecks in major components of database management systems. Then, it demonstrates the data and work sharing opportunities for analytical workloads, and reviews advanced scheduling mechanisms that are aware of non-uniform memory accesses and alleviate bandwidth saturation.
Fiber Optic Flexural Disk Microphone (1989)

A microphone consisting of a hollow cylinder whose flexible, circular endplates are bonded to pairs of flat spiral wound coils of optical fiber is described. When the endplate/disk is deformed due to a pressure difference, the outer and inner fiber coils experience opposite strains resulting in a &quot;push-pull&quot; optical path length difference which is detected in an all-fiber Michelson interferometer. The close proximity of the interferometric fiber coils, separated by the thin thermally conducting end plate, rejects thermal gradient induced signals. The addition of a second identical endplate and fiber coil pair at the opposite end of the cylinder doubles the acoustic sensitivity while canceling acceleration induced signals. The calculated and measured optical strain of a single plate, single coil sensor using static pressure, acoustic pressure, and acceleration are in good agreement and yield a sensitivity of 21 milliradians per Pascal per meter of optical fiber for an 8.0 cm diameter, 3.0 mm thick plate below its resonance frequency of 3 KHz.
Comparison of optical beam smoothing techniques for inertial confinement fusion and improvement of smoothing by the use of zero-correlation masks (2000)

We present analytic theory and numerical simulations comparing the optical beam smoothing capabilities of the smoothing by spectral dispersion (SSD) technique using random temporal phase modulation, with that of the induced spatial incoherence technique. The analytic theory provides a simple formula for the SSD mode spectrum in the usual case where the phase mask at the focusing lens is random, and its asymptotic limit quantitatively relates the long wavelength mode smoothing to the width of the angular dispersion. With parameters and phase aberration relevant to the National Ignition Facility beams, the SSD simulations show that the large long wavelength components, which are also found in earlier simulations, can be significantly reduced by replacing the independent random phase masks in each pair of adjacent beams by a conjugate pair of zero-correlation masks. These simulations suggest that one can combine zero-correlation masks with random temporal phase modulation and multiple color cycles to achieve SSD smoothing approaching the optical bandwidth limit at all spatial frequencies, without using large angular dispersions.
Labeling of native proteins with fluorescent RAFT polymer probes: application to the detection of a cell surface protein using flow cytometry (2018)

Fluorescent RAFT polymer probes with an activated ester reactive end-group can be advantageously used to label native proteins.
U‐500 insulin: why, when and how to use in clinical practice (2006)

Some patients with type 2 diabetes mellitus (T2DM) have severe insulin resistance. Their insulin requirements are significantly greater. These patients need to take 2-3 injections at the same time to take the correct insulin dose or to redial the insulin pen. When daily insulin requirements are in excess of 300 units/day, the volume of the injected insulin becomes an issue. Large-volume injection can cause discomfort and lead to poor concordance with treatment. Using high-strength insulin e.g. U-500 insulin can reduce the volume of the injected insulin. Despite publications of small case reports or case series, no universal guidelines exist on the use of U-500 insulin. We discuss common sense approaches when considering the use of U-500 insulin in clinical practice.
Highly restricted TCR-α β usage by autoreactive human T cell clones specific for DNA topoisomerase I: recognition of an immunodominant epitope (1997)

Autoantibody responses to DNA topoisomerase I (Topo I) are highly specific to patients with systemic sclerosis (SSc). We recently demonstrated that Topo I-specific T cells are components of the T cell repertoire of patients with SSc and healthy individuals. These autoreactive T cells were essential for the Ag-specific activation of B cells resulting in anti-Topo I Ab production in vitro and therefore are believed to play a central role in autoantibody production. To characterize the Topo I-specific T cell, 15 T cell clones reactive with Topo I were generated from two patients with SSc and three healthy donors, all of whom shared the MHC class II allele DR11. All clones expressed a CD3+CD4+CD8- phenotype and were restricted by HLA-DR. When eight rTopo I fragments were tested individually as Ags, all clones responded to F5, which encodes amino acids 209 through 386 of Topo I, but not to F10, which encodes amino acids 209 through 276, indicating that one or more immunodominant epitopes on Topo I is located between amino acids 276 and 386. Analysis of TCR gene usage showed that the predominant V(alpha) segment of the functionally rearranged TCR-alpha gene was Vdelta5, which was used by seven clones. Most strikingly, all except one T cell clone had functional rearrangements of TCR beta-chain genes using the Vbeta120.la and Jbeta1.1 gene segments. Comparison of the CDR3 sequences of the TCRs revealed limited diversity, and, of note, all clones contained the amino acid motif PGGN (or minor variations) in the CDR3 of their TCR beta-chains. Furthermore, identical beta-chain CDR3 amino acid sequences were encoded by cDNAs generated from T cell clones derived from multiple individuals, including patients with SSc and healthy donors.
The complement dependent cytotoxicity (CDC) immune effector mechanism contributes to anti-CD154 induced immunosuppression. (2002)

The absence of direct and indirect CD40/CD154 pathway signals does not prevent islet allograft acute rejection. Interestingly, MR1 anti-CD154 induces islet allograft tolerance in the absence of CD40/CD154 pathway. In a wild-type major histocompatibility complex (MHC) mismatched strain combination, DST results in accelerated islet allograft rejection. Combination of DST and MR1 anti-CD154 treatment prevents presensitization and permits permanent engraftment. However, administration of CVF abolishes the tolerance induction. Moreover, DST plus MR1 anti-CD154 regiment, a potent tolerizing therapy, does not prevent acute islet allograft rejection when complement C5 deficient DBA/2 mice are used as recipients. Thus, the mechanisms of the tolerizing effects by MR1 anti-CD154 are not limited to blockade of CD40/CD154 signals. The CDC immune effector mechanism contributes to MR1 anti-CD154 induced immunosuppression.
Dual roles of PKM2 in cancer metabolism (2012)

Cancer cells have distinct metabolism that highly depends on glycolysis instead of mitochondrial oxidative phosphorylation alone, known as aerobic glycolysis. Pyruvate kinase (PK), which catalyzes the final step of glycolysis, has emerged as a potential regulator of this metabolic phenotype. Expression of PK type M2 (PKM2) is increased and facilitates lactate production in cancer cells, which determines whether the glucose carbons are degraded to pyruvate and lactate or are channeled into synthetic processes. Modulation of PKM2 catalytic activity also regulates the synthesis of DNA and lipids that are required for cell proliferation. However, the mechanisms by which PKM2 coordinates high-energy requirements with high anabolic activities to support cancer cell proliferation are still not completely understood. This review summarizes the biological characteristics of PKM2 and discusses the dual role in cancer metabolism as well as the potential therapeutic applications. Given its pleiotropic effects on cancer biology, PKM2 represents an attractive target for cancer therapy.
Modifying Ventricular Fibrillation by Targeted Rotor Substrate Ablation: Proof‐of‐Concept from Experimental Studies to Clinical VF (2015)

Targeted rotor substrate ablation suppressed VF in an experimental model and a patient with refractory VF. Further studies are warranted on the efficacy of VF source modulation.
Clinical response to etanercept in polyarticular course juvenile rheumatoid arthritis. (2001)

Our results confirm etanercept is a powerful adjunct in the therapy of polyarticular JRA resistant to conventional treatment regimens.
Effects of cyclosporin A and FK506 on Fc epsilon receptor type I-initiated increases in cytokine mRNA in mouse bone marrow-derived progenitor mast cells: resistance to FK506 is associated with a deficiency in FK506-binding protein FKBP12. (1992)

The inhibitory effects of cyclosporin A (CsA) and FK506 on Fc epsilon receptor type I-initiated increases in cytokine mRNA and the expression of their intracellular binding proteins were studied in interleukin 3 (IL-3)-dependent, mouse bone marrow-derived mast cells (BMMCs). In BMMCs sensitized with IgE anti-trinitrophenyl, CsA inhibited trinitrophenylated bovine serum albumin-induced increases in mRNA for IL-1 beta, tumor necrosis factor alpha (TNF-alpha), and IL-6 in a dose-related manner (IC50 values of 4, 65, and 130 nM, respectively). FK506 did not inhibit hapten-specific increases of mRNA for TNF-alpha or IL-6, and for IL-1 beta the IC50 was greater than 50-fold higher than that of CsA. Neither agent inhibited exocytosis of the endogenous secretory granule mediators beta-hexosaminidase and histamine at the IC50 values for inhibition of increases in cytokine mRNA. BMMCs expressed cyclophilin, and CsA inhibited the phosphatase activity of cellular calcineurin with an IC50 of approximately 8 nM. That CsA inhibited IL-1 beta mRNA accumulation in IgE-activated BMMCs with an IC50 similar to that for inhibition of calcineurin activity, whereas the IC50 values were approximately 20-fold higher for the inhibition of TNF-alpha and IL-6 mRNA, suggests that the induction of TNF-alpha and IL-6 is less dependent upon calcineurin activity than is the induction of IL-1 beta. BMMCs were deficient in the 12-kDa FK506-binding protein FKBP12, but not FKBP13, as assessed by RNA and protein blot analyses. FK506 did not inhibit calcineurin phosphatase activity in BMMCs, even at drug concentrations of 1000 nM. The resistance of BMMCs to inhibition of Fc epsilon receptor type I-mediated increases in cytokine mRNA by FK506 is most likely due to their deficiency of FKBP12 and the related inability to inhibit the activity of calcineurin.