gebhart/patrepeval huggingface dataset:
Ceramide plays a prominent role in MDA‐7/IL‐24‐induced cancer‐specific apoptosis (2009)

Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) uniquely displays broad cancer-specific apoptosis-inducing activity through induction of endoplasmic reticulum (ER) stress. We hypothesize that ceramide, a promoter of apoptosis, might contribute to mda-7/IL-24 induction of apoptosis. Ad.mda-7-infected tumor cells, but not normal cells, showed increased ceramide accumulation. Infection with Ad.mda-7 induced a marked increase in various ceramides (C16, C24, C24:1) selectively in prostate cancer cells. Inhibiting the enzyme serine palmitoyltransferase (SPT) using the potent SPT inhibitor myriocin (ISP1), impaired mda-7/IL-24-induced apoptosis and ceramide production, suggesting that ceramide formation caused by Ad.mda-7 occurs through de novo synthesis of ceramide and that ceramide is required for mda-7/IL-24-induced cell death. Fumonisin B1 (FB1) elevated ceramide formation as well as apoptosis induced by Ad.mda-7, suggesting that ceramide formation may also occur through the salvage pathway. Additionally, Ad.mda-7 infection enhanced expression of acid sphingomyelinase (ASMase) with a concomitant increase in ASMase activity and decreased sphingomyelin in cancer cells. ASMase silencing by RNA interference inhibited the decreased cell viability and ceramide formation after Ad.mda-7 infection. Ad.mda-7 activated protein phosphatase 2A (PP2A) and promoted dephosphorylation of the anti-apoptotic molecule BCL-2, a downstream ceramide-mediated pathway of mda-7/IL-24 action. Pretreatment of cells with FB1 or ISP-1 abolished the induction of ER stress markers (BiP/GRP78, GADD153 and pospho-eIF2alpha) triggered by Ad.mda-7 infection indicating that ceramide mediates ER stress induction by Ad.mda-7. Additionally, recombinant MDA-7/IL-24 protein induced cancer-specific production of ceramide. These studies define ceramide as a key mediator of an ER stress pathway that may underlie mda-7/IL-24 induction of cancer-specific killing.
Dissociation of local nitric oxide concentration and vasoconstriction in the presence of cell-free hemoglobin oxygen carriers (2006)

Cell-free hemoglobin's (CFH) high affinity for nitric oxide (NO) could limit CFH's use as an oxygen-carrying blood replacement fluid because it scavenges NO, causing vasoconstriction and hypertension. However, the extent to which perivascular NO levels change following intravascular administration of hemoglobin (Hb) with different molecular dimensions correlates with vasoconstrictive responses in the microcirculation is unknown. The study objective was to determine vasoconstrictive effects following bolus infusions of (1) alphaalpha cross-linked Hb; (2) polymerized bovine Hb; or (3) polyethylene glycol-decorated Hb (PEG-Hb), by measurements of in vivo microvessel diameter, blood flow, perivascular NO concentration, and systemic hemodynamic parameters. All CFHs caused reductions in perivascular NO levels, not correlated to microvascular responses. PEG-Hb (largest molecular volume) maintained blood flow, while the others caused vasoconstriction and reduced perfusion. All solutions increased mean arterial pressure due to vasoconstriction and blood volume expansion, except for PEG-Hb, which increased blood pressure due to blood volume expansion and maintenance of cardiac output. In conclusion, perivascular NO reduction is similar for all Hb solutions because NO binding affinities are similar; however, effects on vascular resistance are related to the type of molecular modification, molecular volume, and oxygen affinity.
Low Complexity Factorial Pulse Coding of MDCT Coefficients using Approximation of Combinatorial Functions (2007)

Factorial pulse coding, a method which is known to efficiently code an information signal using unit magnitude pulses, involves computation of combinatorial functions. These computations are highly complex as they require many multiply and divide operations on multi-precision numbers, especially when the length of a signal is large or many unit magnitude pulses are used for coding. In this paper, we propose a very low complexity method for approximation of these combinatorial functions. The approximate functions satisfy a property which preserves unique decode-ability of the factorial packing encoding/decoding algorithm. The low complexity computation enables use of factorial packing in encoding/decoding of 144 MDCT coefficients using 28 unit magnitude pulses for the audio coding mode of the EVRC-WB speech coding standard without affecting the number of bits required for coding.
Subcellular localization of human monocyte interleukin 1: evidence for an inactive precursor molecule and a possible mechanism for IL 1 release. (1987)

IL 1 activity, as assayed by the proliferation of responsive mouse thymocytes and a human astrocytoma cell line, was detected on the membrane of 1% paraformaldehyde-fixed activated human monocytes. Resting, unactivated monocytes did not display IL 1 activity. Maximum induction of membrane IL 1 was obtained from monocytes treated with polyclonal activators, such as LPS or Staphylococcus aureus, whereas adherence was a weak inducer of membrane IL 1. Isolated cell compartments as plasma membranes, crude lysosomes, and crude cytosol from activated human monocytes expressed significant IL 1 activity, whereas the endoplasmic reticulum showed no IL 1 activity. Exposure to trypsin of either fixed, activated human monocytes or cell compartments from unfixed monocytes, revealed biologically active IL 1 in the membrane, crude lysosome, and crude cytosol, but not in the endoplasmic reticulum. The IL 1 activity in the purified cytosol, prepared by extraction with digitonin, was considerably increased by the trypsin treatment, whereas the increase in IL 1 activity within crude lysosomes and plasma membranes was less. The cell compartments from nonactivated monocytes did not express active IL 1 and trypsin treatment revealed no active IL 1, suggesting the absence of a pool of the trypsin-sensitive form of IL 1. The data confirm the presence of membrane-bound IL 1 in activated human monocytes and indicate that an inactive precursor molecule can be found in the cytosol of such cells. Furthermore, the absence of IL 1 activity either in its active form or as the inactive precursor in the endoplasmic reticulum suggests that IL 1 is not a conventionally secreted protein. Because IL 1 was found in the cytosol as a precursor and in the lysosomal fractions in an active form, these data suggest that after the synthesis and processing of the cytosolic precursor, the 17-kda IL 1, is released via lysosomal vesicles.
Both circulating and clot-bound plasminogen activator inhibitor-1 inhibit endogenous fibrinolysis in the rat. (1991)

The effects of both clot-bound and circulating plasminogen activator inhibitor-1 (PAI-1) on endogenous fibrinolysis were investigated in a rat model of pulmonary embolism. Iodine-125 fibrin(ogen)-labeled blood-clot homogenates were delivered through the left jugular vein to the lung microvasculature, and the subsequent extent of the clot lysis was monitored by measuring the release of 125I-fibrin degradation products (FDPs) into the blood. Clots that had incorporated activated PAI-1 ex vivo were subsequently protected from dissolution in vivo in a dose-responsive manner (half-maximal concentration [IC50] = 4.3 micrograms/ml). PAI-1-containing clots also resisted lysis, as measured by the release of the specific FDP D-dimer. Plasma levels of plasminogen activator (PA) and PAI activity were unaltered by administration of PAI-1-containing clots, and the clot-protective effects of clot-bound PAI-1 were reversed by exogenous tissue-type plasminogen activator administration. Clot lysis was also inhibited in a dose-responsive manner (IC50 = 58 micrograms/kg) by intravenous bolus delivery of activated PAI-1 to the circulation. The clot-protective effects of circulating PAI-1 were correlated with dose-dependent increases in plasma PAI-1 antigen and activity levels and decreases in plasma PA levels (IC50 = 37 micrograms/ml). There was no evidence of any accumulation of circulating PAI-1 in the lungs. Latent PAI-1, whether delivered with or delivered after the clot homogenates, did not affect the clot-lytic process. Activated and latent PAI-1 was cleared from the circulation in a monophasic manner, with a half-life of approximately 32 and 7 minutes, respectively. The results indicate that both clot-bound and circulating PAI-1 are potent inhibitors of fibrinolysis in vivo. Clot-bound PAI-1 may inhibit PAs in the immediate vicinity of the clots, whereas circulating PAI-1 may act systemically by controlling overall levels of PAs present in the blood.
High-Yield Intra- and Extracellular Protein Production Using Bacillus megaterium (2010)

The Bacillus megaterium protein production system based on the inducible promoter of the xyl operon (P(xylA)) was systematically optimized. Multiple changes in basic promoter elements, such as the -10 and -35 region and the ribosome-binding site, resulted in an 18-fold increase of protein production compared to the production of the previously established system. The production in shaking-flask culture of green fluorescent protein (Gfp) as a model product led to 82.5 mg per g cell dry weight (g(CDW)) or 124 mg liter(-1). In fed-batch cultivation, the volumetric protein yield was increased 10-fold to 1.25 g liter(-1), corresponding to 36.8 mg protein per g(CDW). Furthermore, novel signal peptides for Sec-dependent protein secretion were predicted in silico using the B. megaterium genome. Subsequently, leader peptides of Vpr, NprM, YngK, YocH, and a computationally designed artificial peptide were analyzed experimentally for their potential to facilitate the secretion of the heterologous model protein Thermobifida fusca hydrolase (Tfh). The best extracellular protein production, 5,000 to 6,200 U liter(-1) (5.3 to 6.6 mg liter(-1)), was observed for strains where the Tfh export was facilitated by a codon-optimized leader peptide of YngK and by the signal peptide of YocH. Further increases in extracellular protein production were achieved when leader peptides were used in combination with the optimized expression system. In this case, the greatest extracellular enzyme amount of 7,200 U liter(-1), 7.7 mg liter(-1), was achieved by YocH leader peptide-mediated protein export. Nevertheless, the observed principal limitations in protein export might be related to components of the Sec-dependent protein transport system.
Structural basis of activity and allosteric control of diguanylate cyclase (2004)

Recent discoveries suggest that a novel second messenger, bis-(3'-->5')-cyclic di-GMP (c-diGMP), is extensively used by bacteria to control multicellular behavior. Condensation of two GTP to the dinucleotide is catalyzed by the widely distributed diguanylate cyclase (DGC or GGDEF) domain that occurs in various combinations with sensory and/or regulatory modules. The crystal structure of the unorthodox response regulator PleD from Caulobacter crescentus, which consists of two CheY-like receiver domains and a DGC domain, has been solved in complex with the product c-diGMP. PleD forms a dimer with the CheY-like domains (the stem) mediating weak monomer-monomer interactions. The fold of the DGC domain is similar to adenylate cyclase, but the nucleotide-binding mode is substantially different. The guanine base is H-bonded to Asn-335 and Asp-344, whereas the ribosyl and alpha-phosphate moieties extend over the beta2-beta3-hairpin that carries the GGEEF signature motif. In the crystal, c-diGMP molecules are crosslinking active sites of adjacent dimers. It is inferred that, in solution, the two DGC domains of a dimer align in a two-fold symmetric way to catalyze c-diGMP synthesis. Two mutually intercalated c-diGMP molecules are found tightly bound at the stem-DGC interface. This allosteric site explains the observed noncompetitive product inhibition. We propose that product inhibition is due to domain immobilization and sets an upper limit for the concentration of this second messenger in the cell.
Exceptional Resistance of Human H2 Glioblastoma Cells to Complement-Mediated Killing by Expression and Utilization of Factor H and Factor H-Like Protein 1 (2000)

Of over 20 nucleated cell lines we have examined to date, human H2 glioblastoma cells have turned out to be the most resistant to complement-mediated cytolysis in vitro. H2 cells expressed strongly the membrane attack complex inhibitor protectin (CD59), moderately CD46 (membrane cofactor protein) and CD55 (decay-accelerating factor), but no CD35 (complement receptor 1). When treated with a polyclonal anti-H2 Ab, anti-CD59 mAb, and normal human serum, only 5% of H2 cells became killed. Under the same conditions, 70% of endothelial-like EA.hy 926 cells and 40% of U251 control glioma cells were killed. A combined neutralization of CD46, CD55, and CD59 increased H2 lysis only minimally, demonstrating that these complement regulators are not enough to account for the resistance of H2 cells. After treatment with Abs and serum, less C5b-9 was deposited on H2 than on U251 and EA.hy 926 cell lines. A reason for the exceptional resistance of H2 cells was revealed when RT-PCR and protein biochemical methods showed that the H2 cells, unlike the other cell lines tested, actively produced the soluble complement inhibitors factor H and factor H-like protein 1. H2 cells were also capable of binding human factor H from the fluid phase to their cell surface and promoted the cleavage of C3b to its inactive form iC3b more efficiently than U251 and EA.hy 926 cells. In accordance, anti-factor H mAbs enhanced killing of H2 glioblastoma cells. Taken together, our results show that production and binding of factor H and factor H-like protein 1 is a novel mechanism that these malignant cells utilize to escape complement-mediated killing.
Nucleosides. LV. Synthesis of a sulfur-bridged thymine anhydronucleoside and derivatives (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNucleosides. LV. Synthesis of a sulfur-bridged thymine anhydronucleoside and derivativesIris Wempen and Jack J. FoxCite this: J. Org. Chem. 1969, 34, 4, 1020–1025Publication Date (Print):April 1, 1969Publication History Published online1 May 2002Published inissue 1 April 1969https://pubs.acs.org/doi/10.1021/jo01256a056https://doi.org/10.1021/jo01256a056research-articleACS PublicationsRequest reuse permissionsArticle Views103Altmetric-Citations14LEARN 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-Alertsclose Get e-Alerts
PEGylation of Nanocarrier Drug Delivery Systems: State of the Art (2008)

"PEGylation" has become the most widely used method for imparting stealth properties to drug nanocarriers. PEGylation of nanoparticles provides a steric barrier to the adsorption of opsonin proteins due to the neutrality, hydrophilicity, flexibility, and capacity for hydration of the PEG moiety. PEGylation of particle surfaces can be achieved by simple adsorption or through the covalent attachment of PEG to activated functional groups on the surface of the particles. PEG molecules have also been modified to enhance their uptake by specific targets (e.g., tumors) and to achieve the controlled release of entrapped therapeutic agents. Accompanying the prevalence of PEGylation has been the development of a wide variety of characterization techniques and the increasing use of mathematical modeling to guide formulation development. This review summarizes the theories behind PEGylation, PEGylation methodology, the characterization of PEGylated particles, and related mathematical modeling as well as how it can be utilized in the optimization of nanocarrier drug delivery systems. The current successes and failures of PEGylation are evaluated in order to provide a vision for the future of nanocarrier PEGylation and nanomedicine in general.
From chaotic maps to encryption schemes (2002)

Relationship between cryptography and chaos theory, and similarities of their crucial concepts such as: mixing property, and sensitivity to changes in initial conditions and parameters are explained. An example of an encryption algorithm based on chaotic maps is presented.
Incidence and persistence of tardive dyskinesia and extrapyramidal symptoms in schizophrenia (2009)

Although it has been suggested that second-generation antipsychotics (SGA) may reduce the rate of prevalent tardive dyskinesia (TD), little is known about the incidence and outcome of TD in those exposed exclusively to SGA. The incidence and subsequent persistence of TD and extrapyramidal symptoms (EPS) was calculated in a cohort of patients with schizophrenia treated predominantly with SGA. This cohort of more than 10,000 patients with schizophrenia was seen six times over a period of two years. Dichotomous measures of EPS and TD were used to calculate the yearly incidence rates of TD and EPS as well as their subsequent cumulative persistence rate in a subset of 9104 and 6285 patients at risk for TD and EPS, respectively. Of 9104 individuals who did not present with TD at baseline, 138 developed TD, yielding a TD incidence rate of 0.74% (95% CI: 0.62, 0.87) and a subsequent cumulative persistence rate of 80%. Of 6285 individuals without EPS at baseline, 464 developed EPS yielding an incidence rate of 3.7% (95% CI: 3.4, 4.0) and a subsequent cumulative persistence rate of 82%. Incidence rates of TD and EPS may be low in the SGA era. However, once emerged, these disorders prove persistent, suggesting strong moderators effects of underlying predisposing factors.
Validation of cell-based OATP1B1 assays to assess drug transport and the potential for drug–drug interaction to support regulatory submissions (2009)

Transporters are carrier proteins that may influence pharmacokinetic, pharmacodynamic, and toxicological characteristics of drugs. The development of validated in vitro transporter models is imperative to support regulatory submissions of drug candidates. This study is focused on utilizing human embryonic kidney (HEK) 293 cell cultures genetically transfected with the human organic anion transporting polypeptides (OATP) 1B1 transporter to identify substrates and inhibitors in drug development. The kinetics of OATP1B1-mediated uptake of [(3)H]-oestradiol 17beta-glucuronide and inhibition of uptake by rifamycin SV were used to determine K(m), V(max), and IC(50) values over a range of passage numbers to investigate accuracy and precision. The mean K(m) and V(max) values were found to be 6.3 +/- 1.2 microM and 460 +/- 96 pmol min(-1) mg(-1), respectively. The mean IC(50) value for rifamycin SV was 0.23 +/- 0.07 microM on uptake of 1 microM [(3)H]-oestradiol 17beta-glucuronide. These data were similar to previously reported values (accuracy greater than 82%), reproducible (precision less than 29%) and exhibited low standard deviations (SDs) obviating the need to study test compounds on more than one occasion. [(3)H]-oestrone 3-sulfate and [(3)H]-pravastatin exhibited concentration-dependent OATP1B1 uptake, and statistically significant differences were observed at each concentration between uptake rates of HEK293-OATP1B1 and HEK293-MOCK cells (uptake ratios greater than or equal to 3). Propranolol showed no positive uptake ratio. Bezafibrate and gemfibrozil exhibited concentration-dependent inhibition of OATP1B1-mediated uptake of [(3)H]-oestradiol 17beta-glucuronide with mean IC(50) values of 16 and 27 microM, respectively. Based on the validation results, acceptance criteria to identify a test compound as a substrate and/or inhibitor using these specific cell lines were determined. These validated OATP1B1 assays were robust, reproducible, and suitable for routine in vitro evaluation of candidate drugs.
CO 2 laser-induced long-period fibre gratings:spectral characteristics, cladding modes and polarisation independence (1998)

Narrow band, large dynamic range, polarisation independent spectral resonances of long-period fibre gratings fabricated period-by-period with focused CO2 laser pulses are demonstrated at 1490 and 1538 nm. The observed cladding mode near field patterns in this wavelength range are presented.
DNA SYNTHESIS ON ØX174 TEMPLATE DAMAGED BY PROFLAVINE and LIGHT TREATMENT (1982)

Abstract— Onprimed–0X174 single‐stranded DNA photosensitized in the presence of proflavine, Escherichia coli DNA polymerase terminates DNA synthesis at the nucleotide preceding a guanine residue. This chain termination is visualized on a DNA sequencing gel. Our results show that (i) the major targets of the action of proflavine in the DNA are the guanine residues, (ii) there seems no preferential alteration of some residues and (iii) the rate of alteration is very high. We show that the loss of infectivity of 0X174 mediated by the photodynamic action of proflavine can be explained by a block in the DNA polymerisation reaction.
Differentiating prescription omega-3-acid ethyl esters (P-OM3) from dietary-supplement omega-3 fatty acids (2007)

P-OM3 can be used with confidence by practitioners who want to provide therapeutic doses of omega-3 fatty acids in a preparation that has been documented to be both safe and effective.
The Effect of a Fusarium roseum Culture and Diacetoxyscirpenol on Reproduction of White Leghorn Females (1982)

White Leghorn females in egg production (36 weeks old) were fed a culture of Fusarium roseum containing 15 ppm diacetoxyscirpenol (DAS) and other unidentified toxins at culture levels of 0, 1, and 2% of the diet for 8 weeks. Following this, all hens were placed on control (0% toxins) feed for 6 weeks. Birds were inseminated weekly with .05 ml of pooled semen from males given normal diets. The F. roseum had no significant effect on body weight change or egg weights. During the initial 8 weeks, egg production was significantly depressed by both the 1 and 2% levels whereas feed consumption, fertility, and hatchability of fertile eggs was reduced only by the 2% level of F. roseum. Moreover, the majority of embryo mortality occurred prior to the 7th day of incubation. All production levels returned to normal when the toxins were removed during the final 6 weeks. In a second experiment, control (0%), .5 ppm purified DAS, and 3% F. roseum culture were fed to White Leghorn females (50 weeks old) for 4 weeks followed by a 2-week withdrawal period when all birds were given control diets. In 4 weeks, hatchability of fertile eggs was reduced 24% by DAS and 99% by the culture of F. roseum but returned to normal after the toxins were removed. Other production indices were unaffected by dietary treatment. The DAS appears to be only partially responsible for the reduced hatchability; the major toxicant has not been identified.