gebhart/patrepeval huggingface dataset:
Influence of Cremophor El on the bioavailability of intraperitoneal paclitaxel. (2002)

It has been hypothesized that the paclitaxel vehicle Cremophor EL (CrEL) is responsible for nonlinear drug disposition by micellar entrapment. To gain further insight into the role of CrEL in taxane pharmacology, we studied the pharmacokinetics of paclitaxel in the presence and absence of CrEL after i.p. and i.v. dosing. Patients received an i.p. tracer dose of [G-(3)H]paclitaxel in ethanol without CrEL (100 microCi diluted further in isotonic saline) on day 1, i.p. paclitaxel formulated in CrEL (Taxol; 125 mg/m(2)) on day 4, an i.v. tracer of [G-(3)H]paclitaxel on day 22, and i.v. Taxol (175 mg/m(2)) on day 24. Four patients (age range, 54-74 years) were studied, and serial plasma samples up to 72 h were obtained and analyzed for total radioactivity, paclitaxel, and CrEL. In the presence of CrEL, i.v. paclitaxel clearance was 10.2 +/- 3.76 liters/h/m(2) (mean +/- SD), consistent with previous findings. The terminal disposition half-life was substantially prolonged after i.p. dosing (17.0 +/- 11.3 versus 28.7 +/- 8.72 h), as was the mean residence time (7.28 +/- 2.76 versus 40.7 +/- 13.8 h). The bioavailability of paclitaxel was 31.4 +/- 5.18%, indicating insignificant systemic concentrations after i.p. treatment. CrEL levels were undetectable after i.p. dosing (<0.05 microl/ml), whereas after i.v. dosing, the mean clearance was 159 +/- 58.4 ml/h/m(2), in line with earlier observations. In the absence of CrEL, the bioavailability and systemic concentrations of i.p. paclitaxel were significantly increased. This finding is consistent with the postulated concept that CrEL is largely responsible for the pharmacokinetic advantage for peritoneal cavity exposure to total paclitaxel compared with systemic delivery.
Two‐factor requirement for murine megakaryocyte colony formation (1982)

WEHI-3 cell-conditioned medium with the capacity to stimulate megakaryocyte colony formation was separated by Sephadex G-150 column chromatography. The development of colonies containing megakaryocytes was observed only when mixing experiments were performed. Individual fractions did not support megakaryocyte colony growth. The two factors in WEHI-3 CM required for megakaryocyte colony growth had apparent average molecular weights of 35,000 daltons (megakaryocyte CSF) and 100,000 daltons (megakaryocyte potentiator). The results were confirmed in serum-free conditions in which colonies were directly identified in the cultures by acetylcholinesterase staining. Two growth factors may be necessary for the genesis of megakaryocytic colonies.
Different Pathways of Cell Killing by Gossypol Enantiomers (2002)

Gossypol, a polyphenolic, aldehyde-containing constituent of cottonseed, produced partial responses (>50% reduction in tumor size) in some patients with advanced cancer and suppressed sperm as an antifertility agent for men. This action in vivo and its novel side effect profile suggest a specific mechanism of the action of gossypol. Using the random homozygous knockout approach of Li and Cohen (1), we developed a cell line resistant to killing by gossypol, but sensitive to methotrexate and doxorubicin. It showed stereospecific resistance to killing by (-) gossypol (ED(50) 4.9 microM) compared with wild type (ED(50) 2.0 microM). The resistant and wild-type cells were equally sensitive to (+) gossypol (ED(50) 8.8 and 8.4 microM, respectively), methotrexate, and doxyrubicin. We conclude that gossypol affects cells by a stereospecific pathway for (-) gossypol, possibly related to its selective effects, and a nonstereospecific pathway for (+) gossypol and higher concentrations of (-) gossypol. Further knowledge about the stereospecific pathway may lead to new therapeutic drugs.
The sequence, organization, and expression of the major cysteine protease (cruzain) from Trypanosoma cruzi. (1992)

The complete sequence of the gene encoding the major cysteine protease from Trypanosoma cruzi is reported. The amino acid sequence predicted from the gene sequence aligns well with members of the papain family of cysteine proteases, suggesting the name cruzain. The sequence is most closely related to the cysteine protease of Trypanosoma brucei (59.3%) and the murine cathepsin L (42.2%). At least six copies of the gene are present in the genome and are organized in a tandem array of copies which are identical in all restriction endonuclease sites tested. The gene appears to be expressed in all developmental stages of T. cruzi with mRNA levels approximately 2-fold higher in the intracellular amastigote form. A copy of the T. cruzi gene was expressed in bacteria as an inactive, insoluble fusion polypeptide to approximately 5% of the total cell protein. The fusion protein was readily purified, solubilized in urea, and successfully refolded to produce a polyprotein which processed autocatalytically to yield approximately 1 mg of active protease per 3 g of wet cell paste. The processed form of the recombinant protease has an NH2-terminal sequence identical to that of the mature form of the protease purified from T. cruzi (Murta, A. C. M., Persechini, P. M., Souto-Padrón, T., de Souza, W., Guimaraes, J. A., and Scharfstein, J. (1990) Mol. Biochem. Parasitol. 43, 27-38; Cazzulo, J. J., Couso, R., Raimondi, A., Wernstedt, C., and Hellman, U. (1989) Mol. Biochem. Parasitol. 33, 33-42). This suggests that the recombinant protease possesses the requisite specificity and activity to correctly process the proform of the protease in vitro. Kinetic assays with peptide substrates demonstrate that the substrate specificity and kinetic parameters for the recombinant protease are consistent with those of the endogenous protease. The proteolytic activity of the recombinant protease is enhanced by dithiothreitol, inhibited by leupeptin, N alpha-p-tosyl-L-lysine chloromethyl ketone and trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane (E-64) but is unaffected by phenylmethylsulfonyl fluoride, pepstatin, and 1,10-phenanthroline. More specifically, the recombinant enzyme was inhibited by benzyloxycarbonyl-Phe-Arg-fluoromethyl ketone, which inhibits replication and differentiation of T. cruzi within mammalian cells in culture.
Surface Chemistry for Atomic Layer Growth (1996)

Atomic layer controlled film growth is an important technological and scientific goal that is closely tied to many issues in surface chemistry. This article first reviews the basic concepts of atomic layer growth using molecular precursors and binary reaction sequence chemistry. Many examples are given for the various films that have been grown using this atomic layer growth technique. The paradigms for atomic layer epitaxy (ALE) and atomic layer processing (ALP) are then discussed in terms of self-limiting surface reactions. Recent investigations of the surface chemistry of SiO2 and Al2O3 ALP and GaAs ALE are examined and used to illustrate the possible mechanisms of atomic layer growth. Subsequently, the characteristics of film deposition using atomic layer growth techniques are explored using recent examples for Al2O3 ALP. The structure of the deposited films is also reviewed using results from previous Al2O3 deposition investigations. This article then concludes by discussing possible complications to studies of atomic layer controlled growth using binary reaction sequence chemistry.
Cover Picture: Macromol. Chem. Phys. 19/2005 (2005)

Cover: Copolymerizations of ethylene and disubstituted diallylsilanes (A 2 R 2 Si) (CH 2 CHCH 2 ) 2 R 2 Si (R = CH 3 , C 6 H 5 ) have been investigated with zirconocene catalysts. The stereospecific catalysts showed higher reactivity for A 2 R 2 Si monomers than the aspecific ones. A 2 R 2 Si monomers were incorporated in the polymer chain via cyclization insertion, and formed 3,5‐disubstituted silacyclohexane unit. Further details can be found in the Full Paper by N. Naga on page 1959.
<title>Fabrication and characterization of a Fabry-Perot-based chemical sensor</title> (1996)

A micromachined silicon Fabry-Perot interferometric sensor is demonstrated as an optical chemical sensor. This sensor is based on the combined nature of the amplifying and tuning characteristics of the Fabry-Perot microcavity structure and the doping effect of polymer films such as Poly(3- dodecylthiophene) (P3DDT) upon exposure to an oxidizer, in this case, iodine. The fabricated Fabry-Perot chemical sensors show reversible sensing behavior with a maximum change in transmitted optical intensity of 60%. Significant improvement of the sensing performance is obtained from the Fabry-Perot microcavity structure compared to a simple planar single membrane structure, which indicates the resonant effect of the Fabry-Perot cavity on the chemical sensor. The measured sensing characteristics suggest that the change in absorptance of P3DDT polymer inside the microcavity plays a major role, while the deflection of a microcavity membrane by the P3DDT polymer-induced surface tension gives tunability of the sensor to maximize the amplification of output response by adjusting the Fabry- Perot microcavity gap spacing.
Validation of liquid biopsy: plasma cell-free DNA testing in clinical management of advanced non-small cell lung cancer (2018)

Plasma cell-free tumor DNA, or circulating tumor DNA (ctDNA), from liquid biopsy is a potential source of tumor genetic material, in the absence of tissue biopsy, for <i>EGFR</i> testing. Our validation study reiterates the clinical utility of ctDNA next generation sequencing (NGS) for EGFR mutation testing in non-small cell lung cancer (NSCLC). A total of 163 NSCLC cases were included in the validation, of which 132 patients had paired tissue biopsy and ctDNA. We chose to validate ctDNA using deep sequencing with custom designed bioinformatics methods that could detect somatic mutations at allele frequencies as low as 0.01%. Benchmarking allele specific real time PCR as one of the standard methods for tissue-based <i>EGFR</i> mutation testing, the ctDNA NGS test was validated on all the plasma derived cell-free DNA samples. We observed a high concordance (96.96%) between tissue biopsy and ctDNA for oncogenic driver mutations in Exon 19 and Exon 21 of the <i>EGFR</i> gene. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of the assay were 91.1%, 100% 100%, 95.6%, and 97%, respectively. A false negative rate of 3% was observed. A subset of mutations was also verified on droplet digital PCR. Sixteen percent EGFR mutation positivity was observed in patients where only liquid biopsy was available, thus creating options for targeted therapy. This is the first and largest study from India, demonstrating successful validation of circulating cell-free DNA as a clinically useful material for molecular testing in NSCLC.
Evaluation of repair phase and size tolerance for a phase-shift mask (1993)

The conjugate twin-shifter method for alternating phase-shift method provides the flexibility for mask shifter layout, and is applied for both isolated and periodic shifter arrays in conventional i-line positive resist processes. A new mask structure simplifies shifter pattern delineation and reduces the effects of phase defects. The detail of intermediate phase interference has been analyzed by applying the two-dimensional shifter array as the phase defect. The results of this analysis provides the optimum repair element array for the new repair method of phase defects. Then the effectiveness of this simple repair method is examined in the i-line process by using the test arrays that delineated in the XeF2 assisted focused ion beam process.
Niche-Specific Features of the Intestinal Bacteroidales (2007)

By analyzing the genomic sequences of 12 Bacteroidales species, we found that all intestinal species have numerous polysaccharide biosynthesis loci, many with promoters that we demonstrate undergo DNA inversion. This feature is not conserved in the Bacteroidales order as a whole, as oral species do not share these genetic features.
Effect of Metformin in Pediatric Patients With Type 2 Diabetes (2002)

Metformin was shown to be safe and effective for treatment of type 2 diabetes in pediatric patients.
Peptidomimetics Protocols (1998)

Many physiologically important receptors and enzymes are regulated by their endogenous ligands and inhibitors. Nature chose to utilize these p- tides as chemical switches since they can be efficiently
Improving Major Depressive Episode Assessment: A New Tool Developed by Formal Psychological Assessment (2017)

<b>Aim:</b> Major depressive episode (MDE) can manifest with different features. Discriminating between different types of MDEs is crucial for proper treatment. The aim of this study is to propose a new tool for MDE assessment in bipolar disorder (BD) or major depressive disorder (MDD) to overcome some limitations of current rating scales. The proposed tool investigates all of the clinical features of different MDEs and gives qualitative information, differentiating patients with the same score but different symptoms and psychopathology severity. To achieve this purpose authors used a new methodology called Formal Psychological Assessment (FPA). FPA allows creating relations between the items of an assessment tool, and the set of diagnostic criteria of a given clinical disorder. In the application at hand, given the capability to analyze all clinical features, FPA appears a useful way to highlight and differentiate between inhibited and agitated depressive symptoms. <b>Method:</b> The new tool contains 41 items constructed through 23 clinical criteria from the DSM-5 and literature symptoms. In line with FPA, starting from a set of items and a set of clinical criteria, a Boolean matrix was built assigning to each item its own set of clinical criteria. The participants include 265 in the control group and 38 patients with MDE (diagnosed with MDD or BD) who answered the QuEDS. After 1 month, 63 participants performed the test again and 113 took the Depression-Anxiety-Stress Scale to analyze convergent-divergent validity. <b>Results:</b> The scale showed adequate reliability and validity. A hierarchical confirmatory factor analysis highlighted the presence of three sub factors (affective, somatic, and cognitive) and one high-order factor (depression). <b>Conclusions:</b> The new tool is potentially able to inform clinicians about the patients' most likely diagnostic configuration. Indeed, the <i>clinical state</i> of a patient consists of the subset of items he/she answered affirmatively, along with his/her subset of specific symptoms. Qualitative information is fundamental from a clinical perspective, allowing for the analysis and treatment of each patient according to his/her symptoms in an effective way.
Functional and Morphological Improvement of Dystrophic Muscle by Interleukin 6 Receptor Blockade (2015)

The anti-inflammatory agents glucocorticoids (GC) are the only available treatment for Duchenne muscular dystrophy (DMD). However, long-term GC treatment causes muscle atrophy and wasting. Thus, targeting specific mediator of inflammatory response may be more specific, more efficacious, and with fewer side effects. The pro-inflammatory cytokine interleukin (IL) 6 is overproduced in patients with DMD and in the muscle of mdx, the animal model for human DMD. We tested the ability of inhibition of IL6 activity, using an interleukin-6 receptor (Il6r) neutralizing antibody, to ameliorate the dystrophic phenotype. Blockade of endogenous Il6r conferred on dystrophic muscle resistance to degeneration and alleviated both morphological and functional consequences of the primary genetic defect. Pharmacological inhibition of IL6 activity leaded to changes in the dystrophic muscle environment, favoring anti-inflammatory responses and improvement in muscle repair. This resulted in a functional homeostatic maintenance of dystrophic muscle. These data provide an alternative pharmacological strategy for treatment of DMD and circumvent the major problems associated with conventional therapy.
Molecular Mechanisms of Antifibrotic Effect of Interferon Gamma in Bleomycin-Mouse Model of Lung Fibrosis: Downregulation of TGF-β and Procollagen I and III Gene Expression (1995)

The present study was undertaken to elucidate the mechanism for the antifibrotic effect of interferon gamma (IFN-gamma) in the bleomycin (BL)-mouse model of lung fibrosis. The expression of transforming growth factor (TGF-beta) and procollagen I and III and their mRNAs was investigated in the BL-mouse model of lung fibrosis with and without IFN-gamma treatment by Northern and slot blot analyses. Temporal changes in the content of procollagen and TGF-beta mRNAs in the lungs of mice receiving saline or BL by intratracheal route, with and without IFN-gamma treatment by intramuscular route, were quantitated. The level of TGF-beta mRNA increased rapidly and peaked at day 5, whereas the levels of mRNAs for procollagens alpha 1(I) and alpha 1(III) peaked at 10 days after BL instillation. The peak levels of these mRNAs in BL-treated animals were five- to sevenfold higher than those of the control. The increase in TGF-beta mRNA in the lungs of BL-treated mice preceded the increase in the synthesis of type I and type III procollagen mRNAs. BL treatment also increased the hydroxyproline content significantly from 3 to 14 days as compared to the corresponding saline control groups. A maximal increase to 447 micrograms/lung from 223 micrograms/lung in saline control was obtained at 10 days after instillation. Daily treatment with IFN-gamma markedly reduced the BL-induced increases in the mRNA levels of TGF-beta, and procollagen alpha 1(I) and alpha 1(III) without any effect on the lung level of beta-actin mRNA. IFN-gamma treatment also caused significant reduction in the BL-induced increase in the lung hydroxyproline content from 417 to 283 micrograms/lung at 7 days and from 447 to 264 micrograms/lung at 10 days. It may be concluded from the findings of the present study that the cellular mechanisms for the antifibrotic effect of IFN-gamma in the BL-mouse model of lung fibrosis are to initially downregulate the BL-induced overexpression of TGF-beta mRNA, and subsequently procollagen mRNAs, leading to a decreased collagen content.
Geotrichum Candidum (1957)

SUMMARYFifty-two strains of Geotrichum candidum have been compared on standard culture media. The species is illustrated and emended so as to separate it clearly from others in the genus. Link's original description and figure are chosen as lectotype. A list of 55 synonyms is appended.
Lysophosphatidic acid targets vascular and oncogenic pathways via RAGE signaling (2012)

The endogenous phospholipid lysophosphatidic acid (LPA) regulates fundamental cellular processes such as proliferation, survival, motility, and invasion implicated in homeostatic and pathological conditions. Hence, delineation of the full range of molecular mechanisms by which LPA exerts its broad effects is essential. We report avid binding of LPA to the receptor for advanced glycation end products (RAGE), a member of the immunoglobulin superfamily, and mapping of the LPA binding site on this receptor. In vitro, RAGE was required for LPA-mediated signal transduction in vascular smooth muscle cells and C6 glioma cells, as well as proliferation and migration. In vivo, the administration of soluble RAGE or genetic deletion of RAGE mitigated LPA-stimulated vascular Akt signaling, autotaxin/LPA-driven phosphorylation of Akt and cyclin D1 in the mammary tissue of transgenic mice vulnerable to carcinogenesis, and ovarian tumor implantation and development. These findings identify novel roles for RAGE as a conduit for LPA signaling and suggest targeting LPA-RAGE interaction as a therapeutic strategy to modify the pathological actions of LPA.
Increased Susceptibility of  Thymocytes to Apoptosis in Mice Lacking AIM, a Novel Murine Macrophage-derived Soluble Factor Belonging to the Scavenger Receptor Cysteine-rich Domain Superfamily (1999)

Apoptosis of cells must be regulated both positively and negatively in response to a variety of stimuli in the body. Various environmental stresses are known to initiate apoptosis via differential signal transduction cascades. However, induction of signals that may inhibit apoptosis is poorly understood, although a number of intracellular molecules that mediate inhibition of apoptosis have been identified. Here we present a novel murine macrophage-specific 54-kD secreted protein which inhibits apoptosis (termed AIM, for apoptosis inhibitor expressed by macrophages). AIM belongs to the macrophage scavenger receptor cysteine-rich domain superfamily (SRCR-SF), members of which share a highly homologous conserved cysteine-rich domain. In AIM-deficient mice, the thymocyte numbers were diminished to half those in wild-type mice, and CD4/CD8 double-positive (DP) thymocytes were strikingly more susceptible to apoptosis induced by both dexamethasone and irradiation in vivo. Recombinant AIM protein significantly inhibited cell death of DP thymocytes in response to a variety of stimuli in vitro. These results indicate that in the thymus, AIM functions in trans to induce resistance to apoptosis within DP cells, and thus supports the viability of DP thymocytes before thymic selection.
The generation of SDS-stable HLA DR dimers is independent of efficient peptide binding (1996)

MHC class II molecules can exist in two conformations which can be distinguished on the basis of their stability in SDS. The formation of SDS-stable dimers has been shown to correlate with persistent expression of antigen MHC class II-peptide complexes by murine antigen-presenting cells. HLA DR molecules contain either a Val or a Gly at position 86 of the beta chain, which is located in a conserved and prominent hydrophobic pocket in the peptide binding site. Here we show that Val86-containing DR molecules more frequently select peptides which induce the formation of SDS-stable dimers than Gly86 variants. Using analogues of the influence virus haemagglutinin epitope 307-319 we found that the replacement of the aromatic hydrophobic anchor residue (Tyr)at position 309 by amino acids with an aliphatic hydrophobic side chain resulted in the specific formation of high numbers of SDS-stable Val86-DR but not Gly86-DR dimers. These results indicate that the fit between the first anchor residue and the hydrophobic pocket around Dr beta 86 plays a critical role in the formation of SDS-stable DR dimers. Synthetic analogues of naturally processed DR-associated peptides displayed promiscuity in their capacity to bind to several DR specificities and in their ability to induce the SDS-stable conformation. However, no correlation was observed between binding capacity and the ability to induce the SDS-stable conformation. Since it has been shown that SDS stability can relate to the kinetics of peptide-MHC class II interactions, the definition of the requirements for the formation of SDS-stable HLA class II molecules may be important for the design of effective peptide-based immunomodulation protocols.