gebhart/patrepeval huggingface dataset:
Intratumoral chemotherapy for lung cancer: re-challenge current targeted therapies (2013)

Strategies to enhance the already established doublet chemotherapy regimen for lung cancer have been investigated for more than 20 years. Initially, the concept was to administer chemotherapy drugs locally to the tumor site for efficient diffusion through passive transport within the tumor. Recent advances have enhanced the diffusion of pharmaceuticals through active transport by using pharmaceuticals designed to target the genome of tumors. In the present study, five patients with non-small cell lung cancer epidermal growth factor receptor (EGFR) negative stage IIIa-IV International Union Against Cancer 7 (UICC-7), and with Eastern Cooperative Oncology Group (ECOG) 2 scores were administered platinum-based doublet chemotherapy using combined intratumoral-regional and intravenous route of administration. Cisplatin analogues were injected at 0.5%-1% concentration within the tumor lesion and proven malignant lymph nodes according to pretreatment histological/cytological results and the concentration of systemic infusion was decreased to 70% of a standard protocol. This combined intravenous plus intratumoral-regional chemotherapy is used as a first line therapy on this short series of patients. To the best of our knowledge this is the first report of direct treatment of involved lymph nodes with cisplatin by endobronchial ultrasound drug delivery with a needle without any adverse effects. The initial overall survival and local response are suggestive of a better efficacy compared to established doublet cisplatin-based systemic chemotherapy in (higher) standard concentrations alone according to the UICC 7 database expected survival. An extensive search of the literature was performed to gather information of previously published literature of intratumoral chemo-drug administration and formulation for this treatment modality. Our study shows a favorable local response, more than a 50% reduction, for a massive tumor mass after administration of five sessions of intratumoral chemotherapy plus two cycles of low-dose intravenous chemotherapy according to our protocol. These encouraging results (even in very sick ECOG 2 patients with central obstructive non-small cell lung cancer having a worse prognosis and quality of life than a non-small cell lung cancer in ECOG 0 of the same tumor node metastasis [TNM]-stage without central obstruction) for a chemotherapy-only protocol that differs from conventional cisplatin-based doublet chemotherapy by the route, target site, and dose paves the way for broader applications of this technique. Finally, future perspectives of this treatment and pharmaceutical design for intratumoral administration are presented.
The induction of the human T‐cell growth factor receptor precedes the production of RNA and occurs in the presence of inhibitors of RNA synthesis (1986)

The receptor for T-cell growth factor (TCGF) is an activation antigen that is present in low amounts on a small fraction of resting T lymphocytes. The TCGF receptor on human T cells can be detected with the anti-Tac monoclonal antibody within 7-12 h of stimulating the cells with phytohemagglutinin (PHA). In the current studies, we examined human lymphocytes cultured alone, with PHA, or with PHA plus sufficient actinomycin-D to inhibit RNA synthesis. After varying intervals, aliquots of the lymphocytes were stained with acridine orange (AO) or pyronin-Y(PY) to measure RNA and/or with anti-Tac plus FITC goat anti-mouse Ig. Tac expression began to increase after 6-8 h incubation with PHA, whereas increases in PY or AO staining were not detected until 12 h or later. Furthermore, the initial increase in Tac expression was not affected by sufficient actinomycin-D to block all detectable nucleic acid synthesis. Therefore, it appears that the initial expression of TCGF receptors detected after lymphocyte activation does not require de novo production of RNA.
Liquid‐Phase Parallel Synthesis of 4‐Sulfonylbenzoic Acids. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Exhaled Nitric Oxide in Chronic Obstructive Pulmonary Disease (1998)

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction and a neutrophilic inflammation. Exhaled nitric oxide (NO) may be a marker of disease activity in a variety of lung diseases. We measured exhaled NO in patients with documented COPD and investigated whether the concentration of exhaled NO is related to the severity of disease as defined by lung function. We also investigated whether concentration of exhaled NO was different in COPD patients who received inhaled steroids compared with steroid-naive patients. We studied 13 current smokers with COPD, eight exsmokers with COPD, 12 patients with unstable COPD (exacerbation or severe disease), and 10 smokers with chronic bronchitis without airflow limitation. Exhaled NO levels were significantly higher in patients with unstable COPD (12.7 +/- 1.5 ppb) than in other groups (p < 0.01). Exhaled NO levels were significantly higher in smokers with COPD than in smokers with chronic bronchitis (4.3 +/- 0.5 versus 2.5 +/- 0.5 ppb, p < 0.05), and were even higher in patients with COPD who had stopped smoking (6.3 +/- 0.6 ppb, p < 0.01). Exhaled NO levels showed a significant negative correlation with their lung function assessed by % predicted FEV1 values (r = -0.6, p < 0.001). Exhaled NO levels in patients treated with inhaled steroids were significantly higher compared with steroid-naive patients (8.2 +/- 1.2 ppb versus 5 +/- 0.4 ppb, p < 0.05), but the first group included more severe patients as assessed by lung function. We conclude that exhaled NO could serve as a useful, practical marker for monitoring disease activity in COPD.
Simulation metamodels (1998)

The simulation community has used metamodels to study the behavior of computer simulations for over twenty-five years. The most popular techniques have been based on parametric polynomial response surface approximations. The article discusses developments in this area, including alternative metamodel types and experimental designs.
The role of Varroa and viral pathogens in the collapse of honeybee colonies: a modelling approach (2001)

Summary The ecto‐parasitic mite Varroa destructor is a serious world‐wide pest of the honeybee Apis mellifera and has being linked with the death of millions of colonies, although its role in colony death has remained elusive. A simulation model was developed to explain the link between the mite and collapse of the host bee colony, given that colony death does not always occur. We investigated the effects of two pathogens, deformed wing virus (DWV) and acute paralysis virus (APV), vectored by the mite, on the host colony. Two previously published simulation models, a bee and a mite, were combined and adapted for use in temperate climates with a variety of bee diseases. The model was constructed using Modelmaker® software, which allows the progression of a disease in the host colony to be followed daily. The population dynamics generated by the model were similar to those observed in a natural honeybee colony. When DWV‐ or APV‐transmitting mites were introduced into the colony, its adult worker bee population collapsed either during winter or spring for DWV, or autumn to spring for APV. This corresponds well with field observations of colony death in Europe. The model revealed that DWV initially had little effect on the colony but during late summer, as the population of DWV‐transmitting mites increased, the virus caused a reduction in the number of healthy young bees entering the overwintering population. This imbalance in the age structure of the overwintering bees resulted in the eventual death of the colony during the winter or spring. As few as 2000–3600 mites in autumn could kill a colony. In contrast, APV transmitted by Varroa was only able to kill the honeybee colony if a large (10 000+) mite population was already present when an overt APV infection occurred. It was difficult for APV to become established within the bee population due to it causing rapid host death. The model predicts that the less virulent DWV will become more widely established than the highly virulent APV, and that mite control measures need to be taken prior to the production of overwintering bees.
Preparation of electrically conducting polypyrrole in oil/water microemulsion (2000)

Nanoscopic conducting polypyrrole powder was prepared in an oil/water microemulsion with FeCl3 as a dopant. Compared with solution and conventional emulsion polymerizations, a microemulsion polymerization system increases the yield of the resultant polypyrrole. The results of FTIR spectra and thermal analysis studies indicate that the microemulsion polymerization system increased the extent of the π-conjugation length along the polymer backbone and ordered the arrangement of the macromolecule chains. These two effects bring about enhanced conductivity as well as higher thermal stability of polypyrrole. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 77: 135–140, 2000
Role of IQGAP1, a Target of the Small GTPases Cdc42 and Rac1, in Regulation of E-Cadherin- Mediated Cell-Cell Adhesion (1998)

The small guanosine triphosphatases (GTPases) Cdc42 and Rac1 regulate E-cadherin-mediated cell-cell adhesion. IQGAP1, a target of Cdc42 and Rac1, was localized with E-cadherin and beta-catenin at sites of cell-cell contact in mouse L fibroblasts expressing E-cadherin (EL cells), and interacted with E-cadherin and beta-catenin both in vivo and in vitro. IQGAP1 induced the dissociation of alpha-catenin from a cadherin-catenin complex in vitro and in vivo. Overexpression of IQGAP1 in EL cells, but not in L cells expressing an E-cadherin-alpha-catenin chimeric protein, resulted in a decrease in E-cadherin-mediated cell-cell adhesive activity. Thus, IQGAP1, acting downstream of Cdc42 and Rac1, appears to regulate cell-cell adhesion through the cadherin-catenin pathway.
Tensile strength of single-walled carbon nanotubes directly measured from their macroscopic ropes (2000)

20 mm long ropes consisting of soundly aligned single-walled carbon nanotube (SWNT) ropes, synthesized by the catalytic decomposition of hydrocarbons, were employed for direct tensile strength measurements. The average tensile strength of SWNT rope composites is as high as 3.6±0.4 GPa, similar to that of carbon fibers. The tensile strength of SWNT bundles was extrapolated from the strength of the composites to be 2.3±0.2 to 14.2±1.4 GPa after simply taking into account the volume fraction of SWNT bundles in the minicomposite, and the tensile strength of single SWNTs was estimated to be as high as 22.2±2.2 GPa. The excellent mechanical properties of SWNTs will make them an ideal reinforcement agent for high performance composite materials.
Nuclear Actin‐Binding Proteins as Modulators of Gene Transcription (2005)

Dynamic transformations in the organization of the cellular microfilament system are the driving force behind fundamental biological processes such as cellular motility, cytokinesis, wound healing and secretion. Eukaryotic cells express a plethora of actin-binding proteins (ABPs) allowing cells to control the organization of the actin cytoskeleton in a flexible manner. These structural proteins were, not surprisingly, originally described as (major) constituents of the cytoplasm. However, in recent years, there has been a steady flow of reports detailing not only translocation of ABPs into and out of the nucleus but also describing their role in the nuclear compartment. This review focuses on recent developments pertaining to nucleocytoplasmic transport of ABPs, including their mode of translocation and nuclear function. In particular, evidence that structurally and functionally unrelated cytoplasmic ABPs regulate transcription activation by various nuclear (steroid hormone) receptors is steadily accruing. Furthermore, the recent finding that actin is a necessary component of the RNA polymerase II-containing preinitiation complex opens up new opportunities for nuclear ABPs in gene transcription regulation.
Receptor activator of nuclear factor kappa B ligand in an experimental intervertebral disc degeneration. (2009)

We have demonstrated that RANKL is produced locally, also in soluble form, at the site of injury and also in intact vertebrae and bony structures likely due to altered biomechanics. It seems to be engaged in bone healing and remodelling, essentially proving our working hypothesis. These secondary bone changes could represent part of the degenerative spine disease (spondylarthrosis). RANKL inhibitors, like recombinant human osteoprotegerin (OPG), could be interesting drugs to test, not only in osteoporosis, but also in spondylarthrosis.
Special Edition Using Photoshop CS and Illustrator CS (2004)

Peanut butter and jelly. Time and money. Photoshop CS and Illustrator CS. Some things just go hand-in-hand, which is why Que has created the ultimate reference guide for graphic and web designers: Special Edition Using Photoshop CS and Illustrator CS. This comprehensive book and CD-ROM package will teach you everything you need to know to create visually stunning graphics, websites and publications. The CD-ROM includes trial versions of the software, so you can try out your new skills before investing in the CS upgrade, as well as images, plug-ins and additional Illustrator references. Just like peanut butter and jelly, you and Special Edition Using Photoshop CS and Illustrator CS go together!
Analysis of mutations in the PIK3CA and FGFR3 genes in verrucous epidermal nevus (2013)

Verrucous epidermal nevi are congenital hamartomas composed of keratinocytes and may occur alone or in association with developmental abnormalities. A close relationship between variations in the PIK3CA and FGFR3 genes and the appearance of nevi has been recently reported. Based on that, we performed molecular assays for the identification of E542K, E545G/K and H1047R mutations in the PIK3CA gene and of the R248C mutation in the FGFR3 gene. Interestingly, during the amplification process, we did not observe the PCR product of exon 9 of the PIK3CA gene, a region comprising amino acids 542-545. This strongly suggests the occurrence of a microdeletion of that region and indicates a possible allelic variant, which has not yet being described in the literature.
An Extracellular Loop of the Mannose Phosphotransferase System Component IIC Is Responsible for Specific Targeting by Class IIa Bacteriocins (2010)

Class IIa bacteriocins target a phylogenetically defined subgroup of mannose-phosphotransferase systems (man-PTS) on sensitive cells. By the use of man-PTS genes of the sensitive Listeria monocytogenes (mpt) and the nonsensitive Lactococcus lactis (ptn) species to rationally design a series of man-PTS chimeras and site-directed mutations, we identified an extracellular loop of the membrane-located protein MptC that was responsible for specific target recognition by the class IIa bacteriocins.
The Copper-Mediated Cross-Coupling of Phenylboronic Acids and N-Hydroxyphthalimide at Room Temperature:  Synthesis of Aryloxyamines (2000)

[figure: see text] A novel route to aryloxyamines via the copper-mediated cross-coupling of N-hydroxyphthalimide and phenylboronic acids is reported. The reaction is mediated by selected copper(I) and (II) salts in the presence of pyridine and is tolerant of several functional groups on the phenylboronic acid. The phthallmide group is removed using hydrazine to afford the corresponding aryloxyamine.
Thioredoxin-catalyzed refolding of disulfide-containing proteins. (1986)

Thioredoxin, a known catalyst for reducing protein disulfides, was shown to catalyze efficiently the refolding of pancreatic RNase either from the reduced, denatured form or from the scrambled form containing oxidized but incorrectly paired disulfides. Thioredoxin was 1000-fold more efficient on a molar basis than the model dithiol, dithiothreitol, in reactivating reduced, denatured RNase, suggesting that thioredoxin acts as an efficient catalyst for disulfide interchange. Starting with reduced, denatured RNase, enzyme activity was recovered quantitatively with a t1/2 of 30 hr with 100 microM thioredoxin compared to only a 10-20% recovery of activity in the control using air oxidation. Oxygen further stimulated the effectiveness of thioredoxin severalfold. Thioredoxin was most effective in reactivating inactive scrambled RNase, which contained mispaired disulfides, showing a t1/2 of 2 hr. Reduced thioredoxin was optimal for catalyzing disulfide interchange in scrambled RNase, whereas oxidized thioredoxin was required for reactivation of the reduced, denatured species. Optimal reactivation of scrambled RNase required a mixture of reduced and oxidized thioredoxin. Addition of reduced thioredoxin after initiating refolding of reduced denatured RNase with oxidized glutathione effected a rapid reactivation of RNase, suggesting a two-step model for protein refolding in which the monothiol catalyzes the rapid initial formation of protein disulfides and thioredoxin catalyzes the second step of disulfide interchange. Arguments are presented suggesting that thioredoxin may serve an in vivo role analogous to the protein disulfide-isomerase (EC 5.3.4.1).
Characterization of Polylactic Acid–Polyglycolic Acid Composites for Cartilage Tissue Engineering (2003)

The objective of this study was to determine the effects of scaffold composition on the physical properties, adhesion, and growth of bovine articular chondrocytes on polylactic acid (PLA)/polyglycolic acid (PGA) composites. Nonwoven meshes of PGA were coated with PLA, using a solvent evaporation technique that resulted in composites with fractional PLA contents ranging from 0 to 68%. The compressive modulus of scaffolds increased linearly with the addition of PLA, ranging from less than 1 kPa for PGA to approximately 20 kPa for scaffolds with 68% PLA content. The characteristic degradation time of these scaffolds also increased from approximately 5 days for 0% PLA to 45 days for 68% PLA. Addition of PLA decreased cell seeding efficiency from 48% for 0% PLA scaffolds to 27% for 68% PLA scaffolds. Cells seeded onto 27% PLA scaffolds increased 3-fold in number over 4 weeks in culture, whereas cells seeded onto 68% PLA increased only 2-fold in number. Scanning electron microscopy indicated that cells attached to PGA appeared flat with many small processes, whereas those attached to PLA were more rounded. These studies provide important information for the design of scaffolds for cartilage tissue engineering.
Oxidative DNA Damage Preventive Activity and Antioxidant Potential of Stevia rebaudiana (Bertoni) Bertoni, a Natural Sweetener (2007)

At 0.1 mg/mL, the ethyl acetate extract (EAE) of the crude 85% methanolic extract (CAE) of Stevia rebaudiana leaves exhibited preventive activity against DNA strand scission by *OH generated in Fenton's reaction on pBluescript II SK (-) DNA. Its efficacy is better than that of quercetin. The radical scavenging capacity of CAE was evaluated by the DPPH test (IC50=47.66+/-1.04 microg/mL). EAE was derived from CAE scavenged DPPH (IC50=9.26+/-0.04 microg/mL), ABTS+ (IC50=3.04+/-0.22 microg/mL) and *OH (IC50=3.08+/-0.19 microg/mL). Additionally, inhibition of lipid peroxidation induced with 25 mM FeSO 4 on rat liver homogenate as a lipid source was noted with CAE (IC50=2.1+/-1.07 mg/mL). The total polyphenols and total flavonoids of EAE were 0.86 mg gallic acid equivalents/mg and 0.83 mg of quercetin equivalents/mg, respectively. Flavonoids, isolated from EAE, were characterized as quercetin-3-O-arabinoside, quercitrin, apigenin, apigenin-4-O-glucoside, luteolin, and kaempferol-3-O-rhamnoside by LC-MS and NMR analysis. These results indicate that Stevia rebaudiana may be useful as a potential source of natural antioxidants.
Investigation of Common Variations of ABCB4, ATP8B1 and ABCB11 Genes in Patients with Progressive Familial Intrahepatic Cholestasis (2017)

Background: Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of hepatic disorders that can progress rapidly, leading to cirrhosis and death due to liver failure. Mutations and variations in three genes, including ATP8B1, ABCB11, and ABCB4, have been reported to be the main genetic cause of three subtypes of this disorder including PFIC1, PFIC2, and PFIC3, respectively. Objectives: Therefore, the aim of this study was to investigate more common mutations and variations associated with PFIC considering clinical and Para-clinical features of the disease. Methods: Thirty-five unrelated patients with PFIC from the south of Iran were selected randomly among all PFIC patients referring to Namazi hospital, affiliated to Shiraz University of Medical Sciences. Genomic DNA was extracted from the peripheral blood lymphocytes. Sequences related to these variations were then amplified by PCR in the 35 cholestasis patients and analyzed by SangerÂ® sequencing. Results: The results showed that there was no variation in interest exon of ABCB4. Moreover, in ATP8B1, there was no prevalent mutation and only an unknown significant variation (c.*1101 + 366G > A) was found. However, in the ABCB11 gene, different variations were found including c.1434 + 174G > A, c.1434 + 70C > T, c.1331T > C (p.Val444Ala, a common variant proposed to be associated with cholestasis), c.1309-93G > A, c.1309-165C > T. Also, 11 and 13 cases showed heterozygote and homozygote, respectively, for V444A variation of the ABCB11 gene. Conclusions: The allele frequency of V444A in this study was 52.8%. This variation has been previously implicated with higher frequencies in ICP and DIC than normal subjects, suggesting that this variation may become disease-relevant in certain conditions.
Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning (2012)

Adoptive cell therapy with tumor-targeted T cells is a promising approach to cancer therapy. Enhanced clinical outcome using this approach requires conditioning regimens with total body irradiation, lymphodepleting chemotherapy, and/or additional cytokine support. However, the need for prior conditioning precludes optimal application of this approach to a significant number of cancer patients intolerant to these regimens. Herein, we present preclinical studies demonstrating that treatment with CD19-specific, chimeric antigen receptor (CAR)-modified T cells that are further modified to constitutively secrete IL-12 are able to safely eradicate established disease in the absence of prior conditioning. We demonstrate in a novel syngeneic tumor model that tumor elimination requires both CD4(+) and CD8(+) T-cell subsets, autocrine IL-12 stimulation, and subsequent IFNγ secretion by the CAR(+) T cells. Importantly, IL-12-secreting, tumor-targeted T cells acquire intrinsic resistance to T regulatory cell-mediated inhibition. Based on these preclinical data, we anticipate that adoptive therapy using CAR-targeted T cells modified to secrete IL-12 will obviate or reduce the need for potentially hazardous conditioning regimens to achieve optimal antitumor responses in cancer patients.
Introduction to Quality Engineering: Designing Quality into Products and Processes (1986)

Contents: Variety and Quality. Variability loss and tolerance. Determining tolerances. Tolerance design and experimental design. Offline and online quality control. Parameter design and tolerance design: case study. Experimental design for smaller is better characteristics. Experimental design for larger is better characteristics. Bypassing the S/N ratio: spring experiment. Experimental design for dynamic characteristics.