gebhart/patrepeval huggingface dataset:
Knockdown of Oncogenic KRAS in Non–Small Cell Lung Cancers Suppresses Tumor Growth and Sensitizes Tumor Cells to Targeted Therapy (2011)

Oncogenic KRAS is found in more than 25% of lung adenocarcinomas, the major histologic subtype of non-small cell lung cancer (NSCLC), and is an important target for drug development. To this end, we generated four NSCLC lines with stable knockdown selective for oncogenic KRAS. As expected, stable knockdown of oncogenic KRAS led to inhibition of in vitro and in vivo tumor growth in the KRAS-mutant NSCLC cells, but not in NSCLC cells that have wild-type KRAS (but mutant NRAS). Surprisingly, we did not see large-scale induction of cell death and the growth inhibitory effect was not complete. To further understand the ability of NSCLCs to grow despite selective removal of mutant KRAS expression, we conducted microarray expression profiling of NSCLC cell lines with or without mutant KRAS knockdown and isogenic human bronchial epithelial cell lines with and without oncogenic KRAS. We found that although the mitogen-activated protein kinase pathway is significantly downregulated after mutant KRAS knockdown, these NSCLCs showed increased levels of phospho-STAT3 and phospho-epidermal growth factor receptor, and variable changes in phospho-Akt. In addition, mutant KRAS knockdown sensitized the NSCLCs to p38 and EGFR inhibitors. Our findings suggest that targeting oncogenic KRAS by itself will not be sufficient treatment, but may offer possibilities of combining anti-KRAS strategies with other targeted drugs.
Liposomes for Targeted Delivery of Active Agents against Neurodegenerative Diseases (Alzheimer's Disease and Parkinson's Disease) (2011)

Neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease represent a huge unmet medical need. The prevalence of both diseases is increasing, but the efficacy of treatment is still very limited due to various factors including the blood brain barrier (BBB). Drug delivery to the brain remains the major challenge for the treatment of all neurodegenerative diseases because of the numerous protective barriers surrounding the central nervous system. New therapeutic drugs that cross the BBB are critically needed for treatment of many brain diseases. One of the significant factors on neurotherapeutics is the constraint of the blood brain barrier and the drug release kinetics that cause peripheral serious side effects. Contrary to common belief, neurodegenerative and neurological diseases may be multisystemic in nature, and this presents numerous difficulties for their potential treatment. Overall, the aim of this paper is to summarize the last findings and news related to liposome technology in the treatment of neurodegenerative diseases and demonstrate the potential of this technology for the development of novel therapeutics and the possible applications of liposomes in the two most widespread neurodegenerative diseases, Alzheimer's disease and Parkinson's disease.
Efficacy of cinacalcet administered with the first meal after dialysis: the SENSOR Study (2008)

Administering cinacalcet with the first main meal after dialysis was as effective as administration with food during the dialysis session. Cinacalcet was well tolerated. The incidence of gastrointestinal adverse events appeared to be lower when cinacalcet was administered in the evening.
Low Molecular Weight Polyethylenimine Conjugated Gold Nanoparticles as Efficient Gene Vectors (2010)

Gold nanoparticles (GNPs) conjugated with low molecular weight polyethylenimine (PEI 800 Da) were synthesized, and their characteristics as gene transfection vectors were investigated. The polyethylenimine conjugated GNPs (GNP-PEI800s) can retard plasmid DNA completely at N/P ratios above 4 in electrophoresis on agarose gel, and they also render effective protection of DNA from attack by DNase. TEM imaging revealed that GNP-PEI800s with higher PEI grafting density resulted in more compact and smaller complexes with plasmid DNA, compared to those obtained with lower grafting density ones. These complexes showed high efficiency in gene delivery in monkey kidney cells in vitro. In the absence of serum, GNP-PEI800s can transfect pGL-3 to COS-7 cells 3 to 4 orders more efficient than unmodified PEI800, reaching almost the same magnitude of PEI 25 kDa. More importantly, in contrast to the dramatically lowered efficiency of high molecular weight PEIs such as PEI 25 kDa in the presence of serum, the efficiency of GNP-PEI800s can be retained or even enhanced in serum-containing media. GNP-PEI800 1.3 exhibited transfection efficiency exceeding 60-fold that of PEI 25 kDa in 10% serum medium. All GNP-PEI800s exhibit mild cytotoxicity in comparison with that of PEI 25 kDa.
Synthesis and evaluation of 1-(arylsulfonyl)-2-[(methoxycarbonyl)sulfenyl]-1-methylhydrazines as antineoplastic agents (1986)

1-(Arylsulfonyl)-2-[(methoxycarbonyl)sulfenyl]-1-methylhydrazines, with the potential to function as biological methylating agents, were synthesized and evaluated as antineoplastic agents against the L1210 leukemia and the B16 melanoma in mice. All of the compounds of this class had significant activity against the B16 melanoma, with the most active compound, 2-[(methoxycarbonyl)sulfenyl]-1-methyl-1-[(4- methylphenyl)sulfonyl]hydrazine, producing percent T/C values for B16 melanoma tumor bearing mice of between 182 and 232 at dosage levels of from 12.5 to 50 mg/kg daily for 6 consecutive days. In contrast to the related class of agents, the N,N'-bis(sulfonyl)hydrazines reported earlier by this laboratory,1 the 1-(arylsulfonyl)-2-[(methoxycarbonyl)sulfenyl]-1-methylhydrazines were found to be inactive against the L1210 leukemia in vivo.
Introduction to neural networks for intelligent control (1988)

Neural network architecture is presented as one approach to the design and implementation of intelligent control systems. Neural networks can be considered as massively parallel distributed processing systems with the potential for ever-improving performance through dynamical learning. The nomenclature and characteristics of neural networks are outlined. Two simple examples are presented to illustrate applications to control systems: one is fault isolation mapping, and the other involves optimization of a Hopfield network that defines a clockless analog-to-digital conversion.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Nitro-fatty Acid Formation and Signaling (2008)

A review, on the nitro-fatty acid formation and signaling, discussing mechanisms of fatty acid nitration; chem. reactivities of Nitro-fatty acids; and signaling action of Nitro-fatty acids.
Structure modification and crosslinking of methacrylated polylactide oligomers (2002)

Abstract The effect of molecular architecture on the properties of crosslinked polylactides was studied. D,L ‐Lactide‐based telechelic oligomers with different numbers of arms were functionalized with methacrylic anhydride. Functionalized oligomers were crosslinked with thermal initiation at 90°C, and the mechanical and thermal properties, as well as the gel content, were evaluated. The crosslinking density increased with the number of arms in the oligomers, and the compressive yield strength was built up at the same time. The best mechanical properties (compressive yield strength = 120 MPa, modulus = 2800 MPa, and strain = 5.0%) were obtained with cured polymers prepared with a 100 : 8 ratio of lactide to pentaerythritol. When dimethacrylated butanediol was used as a reactive monomer in curing, polymers with high crosslinking density and mechanical strength were obtained at 37, 60, and 90°C. The use of the reactive monomer also enabled high conversions with photoinitiated crosslinking. Finally, hydrolytic degradation and strength retention were demonstrated. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 3616–3624, 2002
[A study on effectiveness of treatment and prevention of relapse using topical administration of terbinafine in a guinea pig model for tinea pedis]. (1994)

The effectiveness of topical terbinafine (TBF) to tinea pedis was evaluated an animal model in which guinea pigs were experimentally infected through their planta pedis with Trichophyton mentagrophytes, then a 1% TBF or butenafine (BTF) cream was administered topically once daily for 4 consecutive weeks. The therapeutic efficacy was assessed on the basis of recovery of fungal cultures from the planta pedis. The cured guinea pigs were reared in a clean environment that protected the animals from reinfection. The dermal tissues were cultured 2, 4, and 8 weeks post-treatment to examine for relapse of tinea. Complete cure was achieved after 4 weeks of administration of TBF or BTF cream. In animals receiving 4 weeks of treatment with TBF, relapse was not observed up to 8 weeks after the termination of treatment. In animals treated with BTF for 4 weeks, while no relapse occurred 4 weeks after cessation of the treatment, relapse was detected in 2 out of 10 feet at 8 weeks after the termination of treatment. These results suggest that topical TBF is effective in curing the infection and in preventing relapse in a guinea pig model of tinea pedis.
Perspectives in allergen immunotherapy: 2017 and beyond (2017)

The Future of the Allergists and Specific Immunotherapy (FASIT) workshop provides a regular platform for global experts from academia, allergy clinics, regulatory authorities and industry to review developments in the field of allergen immunotherapy (AIT). The most recent meeting, held in February 2017, had two main themes: advances in AIT and hot topics in AIT from the regulatory point of view. The first theme covered opportunities for personalized AIT, advances in adjuvants and delivery systems, and the development of new molecules and future vaccines for AIT. Key topics in the second part of the meeting were the effects of the enactment of European Directive 2001/83 on the availability of allergens for therapy and diagnosis across the EU, the challenges of conducting Phase 3 studies in the field, the future role of allergen exposure chambers in AIT studies and specific considerations in performing AIT studies in the paediatric population. Finally, the group highlighted the forthcoming EAACI guidelines and their particular importance for the standardization of practice in the treatment of allergies. This review presents a comprehensive insight into those panel discussions and highlights unmet needs and also possible solutions to them for the future.
Consensus Proposals for a Unified System of Nomenclature of Hepatitis C Virus Genotypes * (2005)

International standardization and coordination of the nomenclature of variants of hepatitis C virus (HCV) is increasingly needed as more is discovered about the scale of HCV-related liver disease and important biological and antigenic differences that exist between variants. A group of scientists expert in the field of HCV genetic variability, and those involved in development of HCV sequence databases, the Hepatitis Virus Database (Japan), euHCVdb (France), and Los Alamos (United States), met to re-examine the status of HCV genotype nomenclature, resolve conflicting genotype or subtype names among described variants of HCV, and draw up revised criteria for the assignment of new genotypes as they are discovered in the future. A comprehensive listing of all currently classified variants of HCV incorporates a number of agreed genotype and subtype name re-assignments to create consistency in nomenclature. The paper also contains consensus proposals for the classification of new variants into genotypes and subtypes, which recognizes and incorporates new knowledge of HCV genetic diversity and epidemiology. A proposal was made that HCV variants be classified into 6 genotypes (representing the 6 genetic groups defined by phylogenetic analysis). Subtype name assignment will be either confirmed or provisional, depending on the availability of complete or partial nucleotide sequence data, or remain unassigned where fewer than 3 examples of a new subtype have been described. In conclusion, these proposals provide the framework by which the HCV databases store and provide access to data on HCV, which will internationally coordinate the assignment of new genotypes and subtypes in the future.
Lung Volumes and Emphysema in Smokers with Interstitial Lung Abnormalities (2011)

In smokers, interstitial lung abnormalities--which were present on about 1 of every 12 HRCT scans--were associated with reduced total lung capacity and a lesser amount of emphysema. (Funded by the National Institutes of Health and the Parker B. Francis Foundation; ClinicalTrials.gov number, NCT00608764.).
A gene expression screen. (1991)

A gene expression screen identifies mRNAs that differ in abundance between two mRNA mixtures by a subtractive hybridization method. The two mRNA populations are converted to double-stranded cDNAs, fragmented, and ligated to linkers for polymerase chain reaction (PCR) amplification. The multiple cDNA fragments isolated from any given gene can be treated as alleles in a genetic screen. Probability analysis of the frequency with which multiple alleles are found provides an estimation of the total number of up- and down-regulated genes. We have applied this method to genes that are differentially expressed in amphibian tadpole tail tissue in the first 24 hr after thyroid hormone treatment, which ultimately induces tail resorption. We estimate that there are about 30 up-regulated genes; 16 have been isolated.
Biological and genetic characterization of TnphoA mutants of Salmonella typhimurium TML in the context of gastroenteritis (1995)

TnphoA transposon insertion mutants of phoN-negative derivatives of Salmonella typhimurium TML (of human gastroenteritic origin) were selected by growing mutagenized recipient bacteria under a variety of growth conditions. Ninety-seven individual mutants, which expressed alkaline phosphatase, were collected and tested for their ability to invade HEp-2 cells. Seven smooth mutants had a reduced ability to invade HEp-2 cells, and three smooth mutants were consistently more invasive than their corresponding parental strains. One rough mutant was of similar invasiveness and two were of reduced invasiveness when compared with that of parental strains. The seven smooth hypoinvasive mutants, the three smooth hyperinvasive mutants, and the three rough mutant strains were tested for their abilities to invade ileal enterocytes by the rabbit ileal invasion assay described previously (3). All smooth mutants exhibited parental levels of invasiveness. The rough mutants were hypoinvasive in the rabbit ileal invasion assay. The HEp-2 system is therefore not a good predictor of behavior in gut tissue in this model. DNA sequences flanking the transposon were determined for five mutants which were hypoinvasive in the HEp-2 cell assay. The mutations were found to be insertions in two previously identified invasion genes, invG and invH, and in a gene not normally associated with invasion, pagC. These observations lead one to be cautious in the interpretation of the biological significance of data obtained from invasion of tissue culture monolayers when extrapolated to gut tissue.
Isopropyl N-phenylcarbamate affects spindle microtubule orientation in dividing endosperm cells of Haemanthus katherinae baker (1969)

ABSTRACT The mitotic inhibitor isopropyl N-phenylcarbamate (IPC) effects changes in the ultrastructure of the dividing endosperm cells of Haemanthus katherinae. In cells treated with 10 p.p.m. IPC for 0·5–2 h the microtubules lose their parallel alignment and become oriented in radial arrays. These radial arrays are interpreted as micropoles of the spindle apparatus and are thought to be the focal points for the chromosomes as they aggregate into micronuclei. Thus, IPC has a markedly different effect on the structure of the spindle apparatus than colchicine, which is observed at concentrations of 50 p.p.m. for 1 h to destroy the microtubules in Haemanthus. The structure of the microtubules appears unaffected by IPC since those from control and treated cells are similar in diameter (22 nm), in degree of staining, and in sensitivity to the fixation. In addition, the chromosomes and cytoplasmic components such as mitochondria, plastids, dictyosomes, elements of the endoplasmic reticulum, and ribosomes are not structurally modified by treatment with IPC.
Replacement of the active site tyrosine of vaccinia DNA topoisomerase by glutamate, cysteine or histidine converts the enzyme into a site-specific endonuclease (1998)

Vaccinia topoisomerase forms a covalent protein-DNA intermediate at 5'-CCCTT downward arrow sites in duplex DNA. The T downward arrow nucleotide is linked via a 3'-phosphodiester bond to Tyr-274 of the enzyme. Here, we report that mutant enzymes containing glutamate, cysteine or histidine in lieu of Tyr-274 catalyze endonucleolytic cleavage of a 60 bp duplex DNA at the CCCTT downward arrow site to yield a 3' phosphate-terminated product. The Cys-274 mutant forms trace levels of a covalent protein-DNA complex, suggesting that the DNA cleavage reaction may proceed through a cysteinyl-phosphate intermediate. However, the His-274 and Glu-274 mutants evince no detectable accumulation of a covalent protein-DNA adduct. Glu-274 is the most active of the mutants tested. The pH dependence of the endonuclease activity of Glu-274 (optimum pH = 6.5) is distinct from that of the wild-type enzyme in hydrolysis of the covalent adduct (optimum pH = 9.5). At pH 6.5, the Glu-274 endonuclease reaction is slower by 5-6 orders of magnitude than the rate of covalent adduct formation by the wild-type topoisomerase, but is approximately 20 times faster than the rate of hydrolysis by the wild-type covalent adduct. We discuss two potential mechanisms to account for the apparent conversion of a topoisomerase into an endonuclease.
Minimum domain of the Shiga toxin A subunit required for enzymatic activity (1993)

The minimum sequence of the enzymatic (A) subunit of Shiga toxin (STX) required for activity was investigated by introducing N-terminal and C-terminal deletions in the molecule. Enzymatic activity was assessed by using an in vitro translation system. A 253-amino-acid STX A polypeptide, which is recognized as the enzymatically active portion of the 293-amino-acid A subunit, expressed less than wild-type levels of activity. In addition, alteration of the proposed nicking site between Ala-253 and Ser-254 by site-directed mutagenesis apparently prevented proteolytic processing but had no effect on the enzymatic activity of the molecule. Therefore, deletion analysis was used to identify amino acid residue 271 as the C terminus of the enzymatically active portion of the STX A subunit. STX A polypeptides with N-terminal and C-terminal deletions were released into the periplasmic space of Escherichia coli by fusion to the signal peptide and the first 22 amino acids of Shiga-like toxin type II, a member of the STX family. Although these fusion proteins expressed less than wild-type levels of enzymatic activity, they confirmed the previous finding that Tyr-77 is an active-site residue. Therefore, the minimum domain of the A polypeptide which was required for the expression of enzymatic activity was defined as StxA residues 75 to 268.
The impact of the 1996 floods on a tidal sand bank in the Knysna estuary, Western Cape : research in action (2004)

We report on the cumulative effect 
of three flood events during October 
and November 1996, their impact on 
the intertidal banks of the Salt River estuary 
and on a single bank in the Knysna middle 
estuary (19lsupgol/supg01'E; 34 o 04'S) upstream of the 
railway bridge.We found that where land-derived, 
medium-to-fine coversand did not exceed 
0.03 m, the invertebrate fauna survived 
and recovered within two years. Burial to a 
depth of 0.20 m, also over a pre-existing 
marine bank, affected the fauna so that only 
42% of the original numbers were present 
after two years. At a site 100 m southwest of 
the other location, where 0.40-0.50 m of land 
sediment had accumulated over a bank not 
previously exposed even at neap low tide, 
only 6.7% of the pre-flood faunal population 
was evident. Upogebia africanal/Ig (mud prawn), 
once common on the bank, was absent; Callianassa krausil/Ig (sand prawn) was the only 
prawn present.
Lipoprotein (a), an independent cardiovascular risk marker (2016)

Epidemiological and genetic studies have identified elevated levels of lipoprotein (a) ((Lp(a)) as a causal and independent risk factor for cardiovascular diseases (CVD). The Lp(a)-induced increased risk of CVD may be mediated by both its proatherogenic and prothrombotic mechanisms. Several guidelines recommend screening of Lp(a) level; however, there are few treatment options for the management of patients with elevated Lp(a). Several new medications for Lp(a) are under development. PCSK9 inhibitors, apolipoprotein (a)-antisense, and apolipoprotein(B-100)-antisense mipomersen have shown promising results. Lp(a) reduction will continue to be an active area of investigation.
Fine-needle aspiration biopsy of peripheral T-cell lymphomas (2001)

Peripheral T-cell lymphoma is a heterogeneous group of lesions with diverse cytomorphology. Cytologic analysis and immunophenotyping is an accurate method of diagnosing peripheral T-cell lymphoma.
Analysis of a distributed maximum power point tracking tracker with low input voltage ripple and flexible gain range (2016)

Partial shading effects on series‐connected solar cells (modules) motivate the development of distributed maximum power point tracking (DMPPT) technology. This study reviews three dominant DMPPT architectures with preference given to DMPPT tracker technology based on its modularity, gain flexibility and technical maturity for decades of development. Topologies suitable for DMPPT tracker application are investigated. A modified buck–boost converter with reduced input voltage ripple and flexible‐gain range is adopted for DMPPT tracker application. At steady state, the topology can reduce the power oscillation at maximum power point and improve the tracking accuracy without increasing input filter capacitor. The flexibility in gain range makes it well‐suited for many commercial solar energy harvest systems under rapidly varying temperature and illumination conditions. The simulation and experiment of a 15 W low‐power prototype under small voltage scale confirm the feasibility of the proposed converter.
Composition of clove (Syzygium aromaticum) bud oil extracted using carbon dioxide (1990)

Abstract Analysis of clove ( Syzygium aromaticum L) bud oil extracted with liquid and supercritical carbon dioxide shows significant qualitative and quantitative compositional differences compared with oil obtained by the conventional hydrodistillation process. The parameters of pressure, temperature, contact time etc, and also the clove oil components, affect the extraction of the bud flavour from the spice.