gebhart/patrepeval huggingface dataset:
Inhibition of STAT3 Promotes the Efficacy of Adoptive Transfer Therapy Using Type-1 CTLs by Modulation of the Immunological Microenvironment in a Murine Intracranial Glioma (2008)

A variety of cancers, including malignant gliomas, show aberrant activation of STAT3, which plays a pivotal role in negative regulation of antitumor immunity. We hypothesized that inhibition of STAT3 signals would improve the efficacy of T cell adoptive transfer therapy by reversal of STAT3-induced immunosuppression in a murine GL261 intracranial glioma model. In vitro treatment of GL261 cells with JSI-124, a STAT3 inhibitor, reversed highly phosphorylated status of STAT3. Systemic i.p. administration of JSI-124 in glioma-bearing immunocompetent mice, but not athymic mice, resulted in prolonged survival, suggesting a role of adaptive immunity in the antitumor effect. Furthermore, JSI-124 promoted maturation of tumor-infiltrating CD11c(+) dendritic cells and activation of tumor-conditioned cytotoxic T cells, enhanced dendritic cells and GL261 production of CXCL-10, a critical chemokine for attraction of Tc1 cells. When i.p. JSI-124 administration was combined with i.v. transfer of Pmel-I mouse-derived type-1 CTLs (Tc1), glioma-bearing mice exhibited prolonged survival compared with i.p. JSI-124 or i.v. Tc1 therapy alone. Flow cytometric analyses of brain infiltrating lymphocytes revealed that JSI-124-treatment enhanced the tumor-homing of i.v. transferred Tc1 cells in a CXCL-10-dependent fashion. Systemic JSI-124 administration also up-regulated serum IL-15 levels, and promoted the persistence of transferred Tc1 in the host. These data suggest that systemic inhibition of STAT3 signaling can reverse the suppressive immunological environment of intracranial tumor bearing mice both systemically and locally, thereby promoting the efficacy of adoptive transfer therapy with Tc1.
UNIVERSAL DATA COMPRESSION (1985)

International Telemetering Conference Proceedings / October 28-31, 1985 / Riviera Hotel, Las Vegas, Nevada
Fasting-induced reductions in cardiovascular and metabolic variables occur sooner in obese versus lean mice (2010)

It is not uncommon for laboratory animals to be fasted prior to experimentation. Fasting evokes marked reductions in heart rate (HR), blood pressure (BP), heat production and oxygen consumption (VO(2)) in rodents. Mice with diet-induced obesity exhibit elevated HR and BP, and lower VO(2) and heat production in the fed condition versus their lean counterparts. It is unknown whether body composition alters the tempo of response to fasting. We tested the hypothesis that cardiovascular and metabolic responses to fasting are delayed in obese versus lean male C57BL/6J mice. In the fed condition, mice that consumed high-fat (HF, 45% fat) chow for 98 ± 5 days had elevated (P < 0.05) body fat percentage (DEXA), serum leptin (ELISA), HR and BP (72-h biotelemetry), and lower (P < 0.05) heat production and VO(2) (72-h metabolic chamber) versus animals that consumed standard chow (CON, 10% fat; n = 16 per group). HR, BP, VO(2), heat production and serum leptin decreased (all P < 0.05) in response to a 16-h fast (16:00-08:00 h) in both groups. Although the overall fold changes in cardiovascular and metabolic parameters were similar in magnitude among animals, fasting-induced reductions in cardiovascular and metabolic variables occurred ∼4 and ∼7 h earlier (P < 0.05), respectively, in HF versus CON mice. These findings indicate that while metabolic and cardiovascular stress evoked by a 16-h fast at 22°C is not different between HF and CON mice, fasting-induced responses occur sooner in obese animals.
The influence of glucose concentration upon the transport of light in tissue-simulating phantoms (1995)

The effect of glucose upon the transport of light in tissue-simulating phantoms is shown and its possible application for non-invasive glucose monitoring in diabetic patients is discussed. The aim of this paper is to investigate the physical background of this effect. The presence of glucose in an aqueous solution increases its refractive index and therefore has an influence upon the scattering properties of particles suspended in solution. Experimental data on the effect of glucose upon the scattering coefficient and the phase function of aqueous suspensions of spherical polystyrene particles are presented for near-infrared wavelengths and compared to values predicted by Mie theory. The subsequent effect upon light transport in multiple scattering, tissue-simulating phantoms is demonstrated experimentally in a slab geometry and theoretically by applying diffusion theory. It is furthermore shown that optional measurements in the frequency domain allow changes of absorption and scattering coefficient to be separately determined. The possible magnitude of this glucose effect in tissue in vivo is discussed.
Tuning of PID Track Followers for Autonomous Driving (2018)

In this paper, a Proportional-Integral-Differential (PID) controller that facilitates track maneuvering for self-driving cars is proposed. Three different design approaches are used to find and tune the controller hyper-parameters, one of them is specifically proposed in this paper for this specific application. The proposed controller uses only the Cross-Track-Error (CTE) as an input to the controller, whereas the output is the steering command. Extensive simulation studies in complex tracks with many sharp turns, have been carried out to evaluate the performance of the proposed controller at different speeds. The analysis shows that the proposed technique outperforms the other ones. The usefulness and the shortcomings of the proposed tuning mechanism are also discussed in details.
Purified Eicosapentaenoic Acid Reduces Small Dense LDL, Remnant Lipoprotein Particles, and C-Reactive Protein in Metabolic Syndrome (2006)

Eicosapentaenoic acid (EPA), one representative of n-3 unsaturated fatty acids (n-3 PUFAs), is clinically used for its lipid-lowering effects (1). n-3 PUFAs were shown to exert various physiological functions such as antiplatelet actions (by antagonizing effects of arachidonic acid) and plaque stabilization (2,3). Several epidemiological studies have explored antiatherogenic and cardioprotective effects of n-3 PUFA that are abundantly contained in fish oil (4). Dyslipidemia accompanying the metabolic syndrome is often associated with elevated levels of remnant lipoprotein particles and small dense LDL (sdLDL), which are newly recognized risk factors for cardiovascular disease (CVD) (5). It was reported that fish oil improved lipoprotein subclass profiles in subjects with an atherogenic lipoprotein phenotype (6). Besides EPA, docosahexaenoic acid and cholesterol are present in fish oil (7), but it is not clear whether purified EPA independently affects lipoprotein subclass profiles. Therefore, we used purified EPA ethyl ester and examined effects of EPA on atherogenic sdLDL particles and remnant lipoprotein particles in the metabolic syndrome, a precursor of CVD. Furthermore, sdLDL has been reported to synergistically interact with inflammation in pathophysiologic processes leading to CVD (8). Therefore, we simultaneously measured effects of EPA on C-reactive protein (CRP), a marker of inflammation, and examined how alteration of lipoprotein profiles by EPA affects systemic inflammation.

A total of 44 Japanese obese type 2 diabetic patients were recruited in our clinics (Table 1). All patients satisfied the definition and diagnostic criteria of the metabolic syndrome proposed by the National Metabolic Syndrome Criteria Study Group of Japan in 2005 (9). Accordingly, an individual is diagnosed with metabolic syndrome if he or she has central adiposity plus two or more of the following three factors: 1 ) raised concentration of triglycerides …
Distributed Intrusion Detection Systems (2007)

The recent tremendous increase in the malicious usage of the network has made it necessary that an IDS should encapsulate the entire network rather than at a system. This was the inspiration for the birth of a distributed intrusion detection system (DIDS). Different configurations of DIDSs have been actively used and are also rapidly evolving due to the changes in the types of threats. This chapter will give the readers an overview of DIDS and the system architecture. It also highlights on the various agents that are involved in DIDS and the benefits of the system. Finally, directions for future research work are discussed.
Purification of monoclonal antibodies by hydrophobic interaction chromatography under no-salt conditions (2013)

Hydrophobic interaction chromatography (HIC) is commonly used as a polishing step in monoclonal antibody purification processes. HIC offers an orthogonal selectivity to ion exchange chromatography and can be an effective step for aggregate clearance and host cell protein reduction. HIC, however, suffers from the limitation of use of high concentrations of kosmotropic salts to achieve the desired separation. These salts often pose a disposal concern in manufacturing facilities and at times can cause precipitation of the product. Here, we report an unconventional way of operating HIC in the flowthrough (FT) mode with no kosmotropic salt in the mobile phase. A very hydrophobic resin is selected as the stationary phase and the pH of the mobile phase is modulated to achieve the required selectivity. Under the pH conditions tested (pH 6.0 and below), antibodies typically become positively charged, which has an effect on its polarity and overall surface hydrophobicity. Optimum pH conditions were chosen under which the antibody product of interest flowed through while impurities such as aggregates and host cell proteins bound to the column. This strategy was tested with a panel of antibodies with varying pI and surface hydrophobicity. Performance was comparable to that observed using conventional HIC conditions with high salt.
Chronic ethanol-induced heterologous desensitization is mediated by changes in adenosine transport. (1990)

Chronic exposure of cultured cell lines to ethanol results in a heterologous desensitization of receptors coupled to adenylate cyclase via GS, the stimulatory guanine nucleotide regulatory protein. This heterologous desensitization is accompanied by a decrease in alpha S, the GTP-binding subunit of GS. Ethanol-induced accumulation of extracellular adenosine is required for the development of heterologous desensitization. To determine the mechanism underlying the ethanol-dependent increase in extracellular adenosine, we investigated the effects of ethanol on the nucleoside transporter responsible for the bidirectional transport of adenosine into and out of the cell. We found that ethanol specifically and non-competitively inhibited nucleoside uptake. Inhibition of adenosine uptake was primarily due to decreased influx via the nucleoside transporter. Thus, ethanol-induced increases in extracellular adenosine appear to be due to inhibition of adenosine influx. After chronic exposure to ethanol, cells became tolerant to the acute effects of ethanol, i.e. ethanol no longer inhibited uptake and, consequently, no longer increased extracellular adenosine concentration. Taken together with our previous studies, these results suggest that acute ethanol inhibition of adenosine influx leads to an increase in extracellular adenosine which in turn activates adenosine A2 receptors to increase cyclic AMP levels, leading to desensitization of receptor-dependent cyclic AMP signal transduction after chronic exposure to ethanol. We next determined whether the same effects of ethanol also occur in alcoholics. We isolated lymphocytes from alcoholics and non-alcoholics and found that alcoholics had a 75% decrease in basal and adenosine receptor-stimulated cyclic AMP production compared with non-alcoholics. To determine whether these differences were due to exposure to ethanol in vivo or to a possible genetic difference between alcoholics and non-alcoholics, we grew lymphocytes in culture in the absence of ethanol. Adenosine receptor-stimulated cyclic AMP levels were higher in alcoholics than non-alcoholics. Moreover, cultured cells from alcoholics were more sensitive to the effects of chronic alcohol on cyclic AMP signal transduction than cells from non-alcoholics. Our results suggest that the cyclic AMP signal transduction system may reflect a genetic alteration in alcoholics and that studies in cultured lymphocytes may allow us to identify individuals at risk of developing alcoholism.
Biologic agents in the treatment of inflammatory rheumatic diseases (1999)

In 1998, further details on the treatment of patients with rheumatoid arthritis with biologic agents became available. Biologic agents with established efficacy, e.g., the chimeric tumor necrosis factor-alpha monoclonal antibody cA2, were tested in combination with methotrexate (MTX), with evidence of synergistic effects. These trials revealed new, important information on the incorporation of tumor necrosis factor-alpha blocking agents into a treatment regimen of rheumatoid arthritis using established disease-modifying antirheumatic drugs and innovative biologic agents. Clinical trials testing new agents, e.g., T-cell receptor peptides in a double-blind, placebo-controlled fashion represented new developments with regard to T cell-directed treatment principles. In addition, new developments in the preclinical phase are discussed.
Dielectric breakdown mechanisms in gate oxides (2005)

In this paper we review the subject of oxide breakdown (BD), focusing our attention on the case of the gate dielectrics of interest for current Si microelectronics, i.e., Si oxides or oxynitrides of thickness ranging from some tens of nanometers down to about 1nm. The first part of the paper is devoted to a concise description of the subject concerning the kinetics of oxide degradation under high-voltage stress and the statistics of the time to BD. It is shown that, according to the present understanding, the BD event is due to a buildup in the oxide bulk of defects produced by the stress at high voltage. Defect concentration increases up to a critical value corresponding to the onset of one percolation path joining the gate and substrate across the oxide. This triggers the BD, which is therefore believed to be an intrinsic effect, not due to preexisting, extrinsic defects or processing errors. We next focus our attention on experimental studies concerning the kinetics of the final event of BD, during which the gate leakage increases above acceptable levels. In conditions of intrinsic BD, the leakage increase is due to the growth of damage within the oxide in localized regions. Observations concerning this damage are reviewed and discussed. The measurement of the current, voltage, and power dissipated during the BD transient are also reported and discussed in comparison with the data of structural damage. We then describe the current understanding concerning the dependence of the BD current transient on the conditions of electric field and voltage. In particular, as the oxide thickness and, as a consequence, the voltage levels used for accelerated reliability tests have decreased, the BD transient exhibits a marked change in behavior. As the stress voltage is decreased below a threshold value, the BD transient becomes slower. This recently discovered phenomenon has been termed progressive BD, i.e., a gradual growth of the BD spot and of the gate leakage, with a time scale that under operation conditions can be a large fraction of the total time to BD. We review the literature on this phenomenon, describing the current understanding concerning the dependence of the effect on voltage, temperature, oxide thickness, sample geometry, and its physical structure. We also discuss the possible relation to the so-called soft oxide BD mode and propose a simpler, more consistent terminology to describe different BD regimes. The last part of the paper is dedicated to exploratory studies, still at the early stages given the very recent subject, concerning the impact on the BD of materials for the metal-oxide-semiconductor gate stack and, in particular, metal gates.
Efficacy of heat and moisture exchangers after changing every 48 hours rather than 24 hours (1998)

Changing the heat and moisture exchanger after 48 hrs rather than 24 hrs did not affect its technical performance in terms of heat and water preservation of ventilatory gases. There is also some indirect evidence of very few, if any, changes in heat and moisture exchanger resistance. However, other large clinical trials should be undertaken to confirm the safety of extending the time between heat and moisture exchanger change. The heated humidifier, supplied with electric energy maintained high levels of humidification and temperature over the 48-hr study period.
Presence of a Kirsten murine sarcoma virus ras oncogene in cells transformed by 3-methylcholanthrene. (1983)

Oncogenes have previously been reported in the DNAs of mouse fibroblast lines which had become transformed after in vitro exposure to the carcinogen 3-methylcholanthrene. These oncogenes are now shown to be versions of the cellular Kirsten ras gene and are therefore homologous to oncogenes detected in a variety of human tumor DNAs.
Immobilizing DNA on gold via thiol modification for atomic force microscopy imaging in buffer solutions (1993)

Thiols, dialkylsulfides, and dialkyldisulfides are known to be chemisorbed with high affinity on gold. We have prepared DNAs of specific length and sequence carrying thiol groups at each end. For this purpose, primers with an HS-(CH2)6-arm at the 5'-end were used to amplify segments of plasmid DNA via the polymerase chain reaction. These thiolated DNAs bind strongly to the large, ultraflat Au surfaces which we have recently described [Hegner, M. et al. (1993) Surface Sci. 291, 39-46], and can be imaged by AFM in liquids (aqueous solutions or propanol). The lengths obtained in the AFM images are consistent with the DNA being in a native B-conformation.
Subependymal giant cell tumors in tuberous sclerosis complex (2004)

Subependymal giant cell tumors in patients with TSC appear to be of mixed glioneuronal lineage, and, therefore, the current practice of classifying these tumors as astrocytomas merits revision. The clinical diagnosis of SGCT should be made for subependymal lesions in TSC that are associated with symptoms, papilledema, or radiologic evidence of hydrocephalus or interval growth. A diagnosis of probable SGCT should be made when a lesion has the potential to cause obstruction based on size or location. Annual screening by MRI with or without contrast is indicated until at least 21 years of age even if subependymal nodules are absent on initial imaging. A diagnosis of SGCT or probable SGCT warrants more frequent monitoring or surgical intervention.
Preparation of [(1,4,7-Trimethyl-1,4,7-triazacyclononane)Rh(PR3)(H)(CH3)]+ and Its Carbon-Hydrogen Reductive-Elimination and Oxidative-Addition Chemistry (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPreparation of [(1,4,7-Trimethyl-1,4,7-triazacyclononane)Rh(PR3)(H)(CH3)]+ and Its Carbon-Hydrogen Reductive-Elimination and Oxidative-Addition ChemistryChunming Wang, Joseph W. Ziller, and Thomas C. FloodCite this: J. Am. Chem. Soc. 1995, 117, 5, 1647–1648Publication Date (Print):February 1, 1995Publication History Published online1 May 2002Published inissue 1 February 1995https://pubs.acs.org/doi/10.1021/ja00110a025https://doi.org/10.1021/ja00110a025research-articleACS PublicationsRequest reuse permissionsArticle Views316Altmetric-Citations64LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Structural basis for the specific inhibition of protein kinase G, a virulence factor of Mycobacterium tuberculosis (2007)

The pathogenicity of mycobacteria such as Mycobacterium tuberculosis is closely associated with their capacity to survive within host macrophages. A crucial virulence factor for intracellular mycobacterial survival is protein kinase G (PknG), a eukaryotic-like serine/threonine protein kinase expressed by pathogenic mycobacteria that blocks the intracellular degradation of mycobacteria in lysosomes. Inhibition of PknG with the highly selective low-molecular-weight inhibitor AX20017 results in mycobacterial transfer to lysosomes and killing of the mycobacteria. Here, we report the 2.4 A x-ray crystal structure of PknG in complex with AX20017. The unique multidomain topology of PknG reveals a central kinase domain that is flanked by N- and C-terminal rubredoxin and tetratrico-peptide repeat domains, respectively. Directed mutagenesis suggests that the rubredoxin domain functions as a regulator of PknG kinase activity. The structure of PknG-AX20017 further reveals that the inhibitor is buried deep within the adenosine-binding site, targeting an active conformation of the kinase domain. Remarkably, although the topology of the kinase domain is reminiscent of eukaryotic kinases, the AX20017-binding pocket is shaped by a unique set of amino acid side chains that are not found in any human kinase. Directed mutagenesis of the unique set of residues resulted in a drastic loss of the compound's inhibitory potency. Our results explain the specific mode of action of AX20017 and demonstrate that virulence factors highly homologous to host molecules can be successfully targeted to block the proliferation of M. tuberculosis.
Single wheat kernel analysis by near-infrared transmittance : protein content (1995)

Regulatory agencies within the USDA have expressed an interest in single kernel analysis of grain for determination of basic intrinsic properties such as protein content. A study was undertaken to determine the feasibility of measuring protein content of intact wheat kernels using near-infrared transmittance spectrophotometry. Six wheat classes were examined: hard red winter, hard red spring, hard white, soft red winter, soft white, and durum. Five samples per class were used, with each sample represented by 96 randomly drawn kernels. Within each class, single kernel spectra (850-1,050 nm) were calibrated to single kernel protein content using four samples; the remaining sample was set aside for model validation. The chemometric method of partial least squares (PLS) analysis was used. For reference values, the protein content (N X 5.7) of each kernel was measured by combustion. Typical model accuracies of r2 in the range of 0.85-0.93 and standard error of prediction of 0.4-0.9% protein were determined on the validation sets. The number of PLS factors required for optimal model performance ranged from 6 to 14, dependent on wheat class and the type of mathematical transformation on the spectra before modeling. Repeatability measurements on kernels that were reloaded into the kernel clamp indicated that the variance of model-determined protein content caused by kernel positioning was largest for the smaller wheat kernels. Improvement in model performance could probably be attained by the averaging of transmittances taken from several positions on each kernel.