gebhart/patrepeval huggingface dataset:
Depletion of ntracellular Glutathione Contributes to JNK-Mediated Death Receptor 5 Upregulation and Apoptosis Induction by the Novel Synthetic Triterpenoid Methyl-2-cyano-3, 12-dioxooleana-1, 9-dien-28-oate (CDDO-Me)1 (2006)

The novel synthetic triterpenoid methyl-2-cyano-3, 12-dioxooleana-1, 9-dien-28-oate (CDDO-Me) induces apoptosis in human cancer cells, showing potential as a cancer therapeutic agent. We previously demonstrated that CDDO-Me induces a c-Jun N-terminal kinase (JNK)-mediated DR5 expression and apoptosis. This study revealed the mechanism by which CDDO-Me induces JNK activation and subsequent DR5 upregulation and apoptosis. To determine whether CDDO-Me activates JNK and induces DR5 expression and apoptosis via oxidative stress by inducing the generation of reactive oxygen species (ROS), we examined the effects of various antioxidants on JNK activation, DR5 upregulation, and apoptosis induction by CDDO-Me. Thiol antioxidants, including N-acetyl-L-cycteine (NAC), glutathione (GSH) and dithiothrietol (DTT), abrogated CDDO-Me-induced apoptosis. In contrast, nonthiol antioxidants, including butylated hydroxyanisole (BHA), Trolox, mannitol, and Mn(II) tetra(4-benoic acid) porphyrin chloride (MnTBAP), failed to do so, with the exception of vitamin C (Vit C). Accordingly, only thiol antioxidants blocked JNK activation induced by CDDO-Me. CDDO-Me reduced intracellular levels of GSH; this reduction was abrogated only by thiol antioxidants and Vit C. However, CDDO-Me did not promote ROS generation. These results suggest that depletion of intracellular GSH, but not ROS generation, contributes to CDDO-Me-induced JNK activation and apoptosis, at least in our systems. Furthermore, these thiol antioxidants abrogated CDDO-Me-induced DR5 expression, whereas the GSH-depleting agent diethylmaleate also upregulated DR5 expression at concentrations that deplete intracellular GSH, demonstrating that GSH depletion can cause DR5 upregulation. Collectively, we conclude that CDDO-Me activates the JNK pathway via depletion of intracellular GSH, leading to DR5 upregulation and induction of apoptosis.
Inhibition of herpes simplex virus type 2 growth by phosphorothioate oligodeoxynucleotides (1990)

Phosphorothioate homo-oligodeoxynucleotides were found to be potent inhibitors of herpes simplex virus type 2 (HSV-2) but less potent for HSV-1 in cell culture studies. Oligomers with longer chain lengths were more active against HSV-2 than those with shorter ones. Of all the compounds examined, the 28-mer phosphorothioate homo-oligodeoxynucleotides were the strongest inhibitors of HSV-2. The degree of inhibition was related to the base moiety on the order of deoxycytidine = thymidine greater than deoxyadenosine. The inhibition of HSV-2 growth by S-dC28 was dose dependent with a 90% inhibitory dose of 1 microM. At 50 microM, S-dC28 inhibited HeLa S3 cell growth by less than 10%. The anti-HSV-2 activity was time and schedule dependent. The oligomer was most inhibitory to viral growth when present during the 1-h viral adsorption period, and this effect could be enhanced by continuous drug exposure after the adsorption period. S-dC28 was also an effective inhibitor of two HSV-2 drug-resistant mutants: a phosphonoformate-resistant mutant that induces an altered DNA polymerase and a 9-(1,3-dihydroxy-2-propoxymethyl)guanine-resistant mutant that does not induce the viral thymidine kinase. In drug combination studies, phosphonoformate was shown to potentiate the action of S-dC28 against HSV-2 growth. In conclusion, because of their potency and selectivity, phosphorothioate homo-oligodeoxynucleotides are a promising new class of anti-HSV agents.
Using Psilocybin to Investigate the Relationship between Attention, Working Memory, and the Serotonin 1A and 2A Receptors (2005)

Increasing evidence suggests a link between attention, working memory, serotonin (5-HT), and prefrontal cortex activity. In an attempt to tease out the relationship between these elements, this study tested the effects of the hallucinogenic mixed 5-HT1A/2A receptor agonist psilocybin alone and after pretreatment with the 5-HT2A antagonist ketanserin. Eight healthy human volunteers were tested on a multiple-object tracking task and spatial working memory task under the four conditions: placebo, psilocybin (215 microg/kg), ketanserin (50 mg), and psilocybin and ketanserin. Psilocybin significantly reduced attentional tracking ability, but had no significant effect on spatial working memory, suggesting a functional dissociation between the two tasks. Pretreatment with ketanserin did not attenuate the effect of psilocybin on attentional performance, suggesting a primary involvement of the 5-HT1A receptor in the observed deficit. Based on physiological and pharmacological data, we speculate that this impaired attentional performance may reflect a reduced ability to suppress or ignore distracting stimuli rather than reduced attentional capacity. The clinical relevance of these results is also discussed.
Effect of low-dose interleukin-2 on disease relapse after T-cell- depleted allogeneic bone marrow transplantation (1994)

T-cell depletion of donor bone marrow has been associated with an increased risk of disease relapse after allogeneic bone marrow transplantation (BMT). Recombinant interleukin-2 (IL-2), which is capable of increasing the antileukemic activity of peripheral blood lymphocytes obtained from patients who have undergone BMT, has been proposed as a potentially useful agent to reduce the risk of relapse post-BMT. We have previously shown that IL-2 administered to patients at very low doses after BMT is both clinically tolerable and immunologically active. We now report on the clinical outcome of 29 patients treated with low-dose IL-2 after CD6-depleted allogenic BMT for hematologic malignancy. IL-2 was administered by continuous infusion for up to 3 months beginning at a median of 67 days post-BMT. Eligibility requirements for IL-2 therapy included demonstration of stable engraftment and absence of acute grade 2-4 graft-versus-host disease (GVHD). Low-dose IL-2 was well tolerated by the majority of patients, with only 4 of 29 subjects withdrawn early. Acute GVHD developed in only one individual. After 12 weeks of treatment, the mean number of circulating natural killer cells in patients increased 10-fold without any significant change in T-cell number. Of the 25 patients who received > or = 1 month of IL-2, only 6 have relapsed. Relapse rate and disease-free survival (DFS) were determined in the 25 patients who completed at least 4 weeks of IL-2 treatment and compared with historical controls transplanted at our institution for the same conditions and treated with an identical ablative regimen and method of T-cell depletion. Only control patients who had survived disease free for 100 days post-BMT were included in this analysis. Cox's proportional hazards regression model suggested that, compared with control patients without a history of GVHD, patients treated with IL-2 had a lower risk of disease relapse (hazard ratio 0.34; range, 0.14 to 0.82) and superior DFS (hazard ratio 0.39; range 0.18 to 0.87). A randomized controlled trial of IL-2 immunotherapy after T-cell-depleted BMT should now be undertaken.
Prognostic value of indoleamine 2,3-dioxygenase expression in colorectal cancer: effect on tumor-infiltrating T cells. (2006)

IDO-high expression by colorectal tumor cells enables certain cancer subsets to initially avoid immune attack and defeat the invasion of T cells via local tryptophan depletion and the production of proapoptotic tryptophan catabolites. Thus, IDO significantly contributes to disease progression and overall survival in patients with colorectal cancer.
The Elimination of Vacancy-Cluster Formation in Dislocation-Free Silicon Crystals (1971)

In dislocation‐free silicon crystals grown by the floating‐zone technique vacancy clusters are formed. The influence of crystal growth conditions on the cluster formation is studied. Methods for the prevention of vacancy cluster formation during growth, based on a nucleation model, are discussed. In crystals grown by one of these methods vacancy clusters could not be detected.
Lipid bilayer fibers from diastereomeric and enantiomeric N-octylaldonamides (1988)

The aggregation behavior of eight diastereomeric N-octylaldonamides, three enantiomers (galacton, mannon, glucon), and corresponding racemates was investigated mainly by electron microscopy. Head groups with a sterically undisturbed all-anti conformation (galacton, mannon) lead to "whisker"-type aggregates, which appear as rolled up, bilayer sheets in both aqueous and 1,2-xylene gels. One pair of 1,3-syn-positioned OH groups in the all-anti conformation neighboring on the amide group, lead to extremely thin helical whiskers of high curvature in water (glucon) or 1,2-xylene (talon). If the outer OH groups are in syn positions in the all-anti chain conformations, the N-octylamides become highly water-soluble (allon, altron, idon) and form rolled up, bilayer sheets in 1,2-xylene (gulon). The length-to-diameter ratios in the aggregates are often higher than 10^4. The fibers are stabilized by amide hydrogen bonds and/or the hydrophobic effect. They can be conceived as models for prebiotic assemblies, which may lead to condensation biopolymers in aqueous media.
STRUCTURE OF A WHITE-TAILED PRAIRIE DOG BURROW (1992)

(Uploaded by Plazi from the Biodiversity Heritage Library) No abstract provided.
Direct Determination of Benzodiazepines in Biological Fluids by Restricted-Access Solid-Phase Microextraction (2002)

A biocompatible solid-phase microextraction (SPME) fiber was prepared using an alkyl-diol-silica (ADS) restricted-access material as the SPME coating. The ADS-SPME fiber was able to simultaneously fractionate the protein component from a biological sample, while directly extracting several benzodiazepines, overcoming the present disadvantages of direct sampling in biological matrixes by SPME. The fiber was interfaced with an HPLC-UV system, and an isocratic mobile phase was used to desorb, separate, and quantify the extracted compounds. The calculated clonazepam, oxazepam, temazepam, nordazepam, and diazepam detection limits were 600, 750, 333, 100, and 46 ng/mL in urine, respectively. The method was confirmed to be linear over the range of 500-50000 ng/mL with an average linear coefficient (R2) value of 0.9918. The injection repeatability and intraassay precision of the method were evaluated over 10 injections, resulting in a RSD of approximately 6%. The ADS-SPME fiber was robust and simple to use, providing many direct extractions and subsequent determination of benzodiazepines in biological fluids.
Healing of extraction sockets and surgically produced – augmented and non‐augmented – defects in the alveolar ridge. An experimental study in the dog (2005)

Sockets that following tooth removal had their PDL tissue removed exhibited similar features of healing after 3 months as sockets which had the PDL retained. The tissues present in an extraction site appeared to be more mature than those present in a surgically produced defect of similar dimension. The Bio-Oss Collagen augmented defect exhibited less wound shrinkage than the non-augmented defect.
Preclinical studies on targeted delivery of multiple IFNα2b to HLA-DR in diverse hematologic cancers (2011)

The short circulating half-life and side effects of IFNα affect its dosing schedule and efficacy. Fusion of IFNα to a tumor-targeting mAb (mAb-IFNα) can enhance potency because of increased tumor localization and improved pharmacokinetics. We used the Dock-and-Lock method to generate C2-2b-2b, a mAb-IFNα comprising tetrameric IFNα2b site-specifically linked to hL243 (humanized anti-HLA-DR). In vitro, C2-2b-2b inhibited various B-cell lymphoma leukemia and myeloma cell lines. In most cases, this immunocytokine was more effective than CD20-targeted mAb-IFNα or a mixture comprising the parental mAb and IFNα. Our findings indicate that responsiveness depends on HLA-DR expression/density and sensitivity to IFNα and hL243. C2-2b-2b induced more potent and longer-lasting IFNα signaling compared with nontargeted IFNα. Phosphorylation of STAT1 was more robust and persistent than that of STAT3, which may promote apoptosis. C2-2b-2b efficiently depleted lymphoma and myeloma cells from whole human blood but also exhibited some toxicity to B cells, monocytes, and dendritic cells. C2-2b-2b showed superior efficacy compared with nontargeting mAb-IFNα, peginterferonalfa-2a, or a combination of hL243 and IFNα, using human lymphoma and myeloma xenografts. These results suggest that C2-2b-2b should be useful in the treatment of various hematopoietic malignancies.
Identification of (N-acyl)ethanolamine phosphoglycerides and acylphosphatidylglycerol as the phospholipids which disappear as Dictyostelium discoideum cells aggregate (1980)

The cellular slime mold Dictyostelium discoideum contains a phospholipid fraction which comprises 10% of the phospholipids in the early developing amoebae and disappears during the aggregation stage of development. As a first step in studying its metabolism, the composition of the fraction has been determined. It was easily isolated by preparative silicic acid thin-layer chromatography because its Rf was considerably higher than most commonly encountered phospholipids. Its Rf was the same as synthetic phosphatidyl-N-acylethanolamine and synthetic acylphosphatidylglycerol (also called semilysobisphosphatidic acid). Strong absorption peaks characteristic of amide bonds in the infrared spectrum of the isolated D. discoideum phospholipid showed that N-acylethanolamine phosphoglycerides were present. The presence of acylphosphatidylglycerol was revealed when mild alkaline hydrolysis of the lipid fraction produced glycerophosphorylglycerol as the only water-soluble, phosphate-containing product. The composition of the fraction was determined by chemical analysis and thin-layer chromatography of the intact phospholipids and their partially or completely hydrolyzed products. The composition of the fraction was 30% diacylglycerophosphoryl-N-acylethanolamine, 50% alkenylacylglycerophosphoryl-N-acylethanolamine, and 20% acylphosphatidylglycerol. The stereoconfiguration of the glycerophosphorylglycerol moiety of the acylphosphatidylglycerol was found to be sn-3-glycerophosphoryl-sn-1'-glycerol.
Quantum Chemical Analysis of Heteroarylnitrenium Ions and Mechanisms for Their Self-Destruction (2000)

Singlet−triplet state-energy splittings in arylnitrenium ions are substantially reduced when the aromatic system is heterocyclic with nitrogen atoms incorporated at ring positions that would otherwise better stabilize the formally exocyclic positive charge through resonance. Ring contraction rearrangements of singlet arylnitrenium ions with a nitrogen atom at an ortho position are predicted to proceed with barrier heights that become lower with increasing substitution of nitrogen atoms at other positions. Predilection to delocalize positive charge also controls the relative facility with which (i) N-acetylarylnitrenium ions undergo ring closure to form 2-oxazolium cations and (ii) arylnitrenium ions are subject to nucleophilic aromatic substitution by water.
Some sulfhydryl properties and primary structure of human erythrocyte superoxide dismutase (1980)

Human Cu-Zn superoxide dismutase prepared by different methods shows varying properties relevant to its sulfhydryl chemistry. A cysteine residue not found in the analogous bovine enzyme appears to be responsible for its unusual lability. Alkylation of this cysteine results in a marked increase in stability, and this form of the protein may be readily crystallized. The primary structure of the 153 amino acid residues found in the human protein has been determined, and 82% of the residues are identical with those of the bovine enzyme. A significant variation is seen in the portion of those proteins comprising residues 17-36, with eleven changes being noted.
Diagnosis and Classification of 17 Diseases from 1404 Subjects via Pattern Analysis of Exhaled Molecules (2016)

We report on an artificially intelligent nanoarray based on molecularly modified gold nanoparticles and a random network of single-walled carbon nanotubes for noninvasive diagnosis and classification of a number of diseases from exhaled breath. The performance of this artificially intelligent nanoarray was clinically assessed on breath samples collected from 1404 subjects having one of 17 different disease conditions included in the study or having no evidence of any disease (healthy controls). Blind experiments showed that 86% accuracy could be achieved with the artificially intelligent nanoarray, allowing both detection and discrimination between the different disease conditions examined. Analysis of the artificially intelligent nanoarray also showed that each disease has its own unique breathprint, and that the presence of one disease would not screen out others. Cluster analysis showed a reasonable classification power of diseases from the same categories. The effect of confounding clinical and environmental factors on the performance of the nanoarray did not significantly alter the obtained results. The diagnosis and classification power of the nanoarray was also validated by an independent analytical technique, i.e., gas chromatography linked with mass spectrometry. This analysis found that 13 exhaled chemical species, called volatile organic compounds, are associated with certain diseases, and the composition of this assembly of volatile organic compounds differs from one disease to another. Overall, these findings could contribute to one of the most important criteria for successful health intervention in the modern era, viz. easy-to-use, inexpensive (affordable), and miniaturized tools that could also be used for personalized screening, diagnosis, and follow-up of a number of diseases, which can clearly be extended by further development.
Phase I/II trial of the novel Hsp90 inhibitor, IPI-504, in patients with relapsed and/or refractory stage IIIB or stage IV non-small cell lung cancer stratified by EGFR mutation status (2007)

B79 Introduction: Inhibition of the Heat Shock Protein 90 (Hsp90) chaperone protein results in selective destruction of the mutated epidermal growth factor receptor (EGFR) kinase in human non-small cell lung cancer (NSCLC) cell lines and significantly reduces tumor growth in in vivo models, including those resistant to tyrosine kinase inhibitors (TKIs). We designed a phase I/II trial of IPI-504, a water-soluble Hsp90 inhibitor, for patients (pts) with advanced NSCLC who had received prior TKI therapy.  Methods: Patients with Stage IIIB (with malignant effusion) or Stage IV NSCLC who had received prior therapy with an EGFR TKI (e.g., gefitinib or erlotinib) for ≥12 weeks, and had available tissue for EGFR mutation analysis were eligible for treatment. The goal of the Phase I portion was to evaluate the safety and maximum tolerated dose (MTD) of IPI-504 in pts with advanced NSCLC. Once dose-escalation is completed, the Phase II portion will begin with a goal of determining the potential anti-tumor activity of IPI-504 in NSCLC pts, stratified by EGFR mutation status. Pts received IPI-504, IV in 250 cc of normal saline over 30 mins, twice weekly on a four-week cycle. Subjects were evaluated for clinical benefit and radiographic improvement or stabilization by RECIST. Pharmacokinetic profiling of IPI-504 and its major active metabolites (17-AAG and 17-AG) was also performed on all pts.  Results: 8 NSCLC pts have been entered at 3 dose levels (150 mg/m2 IPI-504 [n=3], 225 [3], 300 [2]); 7 females, 1 male; age range 47-83; 7 were positive for EGFR mutation (exon 19del or L858R); avg. # prior therapies 3.7 (range 1-6); All pts completed at least 1 cycle and were evaluated. No objective responses have been observed yet; however, 2 pts had stable disease including 1 pt on therapy for >5 cycles (20 weeks). IPI-504 has been well-tolerated to date; one DLT (grade 3 AST elevation, reversible) was observed at 300 mg/m2. This dose level has been expanded. The MTD has not been reached, and dose escalation in the phase I portion of the study is ongoing.  Conclusions: Targeting Hsp90 represents a novel therapeutic strategy in advanced, metastatic NSCLC patients who have failed prior therapy with TKIs. IPI-504 has been well-tolerated overall, and encouraging preliminary biological activity has been observed with the occurrence of extended stable disease.
Molecular mechanisms of binding and single-strand scission of DNA by the antitumor antibiotics saframycins A and C (1982)

The quinone antitumor antibiotics saframycins A and C bind to duplex DNA and G,C containing complementary oligodeoxyribonucleotides at pHs below 5.5 via selective protonation of the antibiotics at the N-12 positions in an equilibrium process. This binding shows minor groove specificity to T4 DNA for both antibiotics. Saframycin A exhibits an additional mode of covalent binding to DNA, which is reversible by heating, via an animal linkage with the NH2 group of guanine. Covalent binding of saframycin A is enhanced by prior reduction of the quinone moiety via a different mechanism with concomitant elimination of the nitrile group and plausibly involves an intermediate quinone methide. Both saframycin A and saframycin C when reduced in situ with NADPH or sodium borohydride cause single-strand breaks, but not double-strand breaks, in PM2 covalently closer circular DNA. This latter reaction proceeds via intermediate semiquinones, the identity and conformation of which are established by EPR. The DNA scission process which requires oxygen is mediated by the generation of O2-., H2O2 and OH., the latter of which species was identified by spin trapping. The strand scission of DNA is pH dependent and, unlike the binding of the antibiotics, is strongly inhibited by Mg2+ and Zn2+ ions.
In vivo magnetic resonance imaging of sodium in the human body (1988)

Sodium magnetic resonance imaging of the human body in vivo has been tried and its clinical application is considered. A short T2 imaging algorithm with total volume excitation and a specialized RF coil focused to the region of interest have been adopted to improve the signal-to-noise ratio. Using a 1.5-T human body imaging system, several important organs including heart, liver, gallbladder, kidney, and spine have been examined to demonstrate their sodium concentration in vivo.
Interaction of complement with Neisseria meningitidis and Neisseria gonorrhoeae (1989)

The importance of the complement system in host defense against systemic infection caused by neisseriae is emphasized by a number of clinical observations documenting the importance of antibody-dependent, complement-mediated serum bactericidal activity in protection from systemic meningococcal disease (17) and the well-recognized association between the resistance of gonococci to complement-dependent serum bactericidal activity and the development of disseminated gonococcal infection (46, 49). Moreover, individuals with inherited complement deficiencies have a markedly increased risk (ca. 6,000-fold) of acquiring systemic neisserial infections and are subject to recurrent episodes of systemic meningococcal and gonococcal infections (37, 43). The purpose of this report is to review the complement cascade with particular reference to its importance in host defense against bacterial diseases, to compare and contrast neisserial disease in complement-deficient and complementsufficient individuals, to examine the molecular and functional basis for the particular importance of complement in host defense against these infections, and to examine the immunologic basis for prevention of neisserial disease in complement-deficient individuals.