gebhart/patrepeval huggingface dataset:
Epidermal Growth Factor Receptor (EGFR) Targeted Therapies in Non- Small Cell Lung Cancer (NSCLC) (2006)

The Epidermal Growth Factor Receptor (EGFR) family, including EGFR, HER2, HER3, and HER4, is implicated in the development and progression of cancer, and is expressed in many human epithelial malignancies, including Non-Small Cell Lung Cancer (NSCLC). Several molecules were synthesized to inhibit the extracellular domain of EGFR, such as cetuximab (Erbitux), the extracellular domain of HER2, such as trastuzumab (Herceptin) or the EGFR tyrosine kinase domain, such as gefitinib (Iressa) and erlotinib (Tarceva). Gefitinib and erlotinib are orally active, selective EGFR tyrosine-kinase inhibitors (EGFR-TKI) that produce objective response rates in about 10% of advanced NSCLC. More recently, erlotinib produced a significant improvement in survival when compared to placebo in pretreated NSCLCs. Among clinical characteristics, although female gender, and adenocarcinoma histology, showed to be significantly associated to TKI sensitivity, never smoking history is probably the most relevant factor. Presence of specific EGFR gene mutations or EGFR gene amplification confer a particularly sensitive phenotype, and patients with activation of the anti-apoptotic protein Akt are more sensitive, when Akt activation is sustained by a EGFR dependent mechanism. Cetuximab is a human-murine chimeric anti-EGFR IgG monoclonal antibody that has demonstrated both in vitro and in vivo antitumor activity in tumor cell lines expressing EGFR. It has shown impressive activity when combined with radiation by increasing the antitumor effect of radiation therapy. Cetuximab has a synergistic effect with cisplatin and may play a role in reversing resistance to chemotherapy. Cetuximab demonstrated to be active in pretreated NSCLCs, and its activity as first-line therapy in combination with chemotherapy is currently under evaluation. Efforts should be made for the identification of biological mechanism underlying cetuximab sensitivity and emerging data suggest that the drugs is more active in patients with EGFR gene amplification. In NSCLC, trastuzumab produced disappointing results when combined with chemotherapy, but probably patients were not properly selected. Recent findings in gefitinib treated patients support HER2 analysis by fluorescence in situ hybridization as a complementary test for selection of patient candidate for EGFR targeted therapies. Combination of EGFR targeting agents with other biological drugs is under investigation.
Intensification of Enzymatic Reactions in Heterogeneous Systems by Low Intensity, Uniform Sonication: New Road to "Green Chemistry" (2007)

Enzymatic bio-processing of various substrates generates significantly less wastewater effluents that are readily biodegradable, and do not pose an environmental threat. However, two major shortcomings that impede acceptance by industry are expensive processing costs and slow reaction rates. Enzymatic bio-processing of cotton textiles with cellulase and pectinase enzyme processing solutions, under low energy, uniform sonication greatly improved the efficiency of the enzymes and significantly increased the overall reaction rates. Specific critical features of combined enzyme/ultrasound bio-processing are: a) cavitation effects that enhance the transport of enzyme macromolecules toward the substrate surface, b) the several hundred fold greater effect of cavitation in heterogeneous than homogeneous systems, and c) the maximum effects of cavitation at ~50 °C that are optimum temperature for most enzymatic reactions. Contrary to common belief, low intensity, uniform sonication does not damage or inactivate sensitive structures of enzyme protein macromolecules. Overall, under specific conditions, carefully controlled introduction of ultrasound energy during enzymatic bio-processing has an excellent potential for the intensification of a variety of technological processes that involve many types of industrial enzymes and substrates.
Increased Matrix Metalloproteinase-9 in the Airway after Allergen Challenge (2000)

Persistent asthma is associated with airway inflammation, tissue damage, and deposition of extracellular matrix (ECM) proteins, which may be mediated, in part, through release of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase-1 (TIMP-1). To investigate the role of allergen in the induction of MMP-9 and TIMP-1, bronchoscopy and segmental bronchoprovocation (SBP) with saline (SAL) and antigen (AG) were performed in 17 allergic subjects. Bronchoalveolar lavage (BAL) was done 5 min and 48 h after challenge and concentrations of MMP-9 and TIMP-1 in BAL fluid (BALF) were measured by ELISA. Forty-eight hours after AG challenge, concentrations of MMP-9 and TIMP-1 were increased in the airway, but not in serum. Zymography demonstrated that MMP-9 was the predominant metalloproteinase and was present in a latent proform. MMP-9 immunoreactivity was associated primarily with neutrophils, and concentrations of MMP-9 in BALF correlated with airway neutrophils and, to a lesser extent, with alveolar macrophages. These data suggest that AG challenge leads to generation of factors, including MMP-9, that may be associated with the initiation of bronchial injury, which may then lead to remodeling in asthma.
Roles of mast cell tryptase and chymase in airway function (1989)

Mast cells are abundant and are widely distributed in airway tissues. They release their secretory products into microenvironments as diverse as epithelium, smooth muscle, and glands. The major secretory granule proteins of mast cells are proteases that are released outside of the cell with heparin, histamine, and other preformed mediators. In the past few years, investigations in a number of laboratories have rapidly increased our knowledge of the chemical and biological properties of the two major mast cell secretory proteases, tryptase and chymase. Recent experimental evidence suggests the possibility of biologically important roles for tryptase and chymase in the airways, particularly in the regulation of neuropeptide activity, bronchomotor tone, and submucosal gland secretion. The purpose of this commentary is to examine critically the evidence of participation of these mast cell proteases in molecular and physiological events in the airways.
Soft x-ray excited optical luminescence: Some recent applications (2002)

X-ray excited optical luminescence (XEOL) studies of several classes of light emitting materials excited using soft x rays (photon energy ranging from 10 to 2500 eV) are presented. We show that XEOL with soft x rays (short penetration depths) is often site specific and is ideally suited for the study of light emitting thin films and devices. Several examples including porous silicon, organic light emitting diode materials, and CdS based nanostructures are used to illustrate the unique properties of XEOL and its applications in the soft x-ray energy region.
Retention of Viral Antigen in the Cytoplasm of Cells Infected with Temperature-Sensitive Mutants of an Avian Adenovirus (1970)

Immunofluorescent studies were made on chicken kidney cell cultures infected with various temperature-sensitive (ts) mutants of an avian adenovirus, chicken embryo lethal orphan (CELO), which grow well at the nonrestrictive temperature of 31 degrees , but fail to grow at the restrictive temperature of 40 degrees . At 40 degrees some mutants (ts 5, 8, and 10) accumulated viral antigen in the cytoplasm, but scarcely at all in the nucleus. However, at 31 degrees they accumulated the antigen in the nucleus like the wild-type strain at either 31 degrees or 40 degrees . These mutants seemed to complement each other in nuclear accumulation of antigen at 40 degrees . In cells infected with ts 8, the antigen remaining in the cytoplasm during incubation at 40 degrees was partially transferred to the nucleus even in the presence of an inhibitor of protein synthesis when the temperature was lowered to 31 degrees . The results suggest that viral antigen produced in the cytoplasm is transported to the nucleus and that these ts mutants are defective in this process at 40 degrees .There are apparently two other types of ts mutant: one type (ts 3, 7, and 12), like the wild-type strain, showing nuclear accumulation of antigen at 40 degrees and the other (ts 6, 11, and 17) showing no, or only slight, formation of the antigen at 40 degrees .
Release of Satiety Hormones in Response to Specific Dietary Proteins Is Different between Human and Murine Small Intestinal Mucosa (2010)

Pea and wheat protein are the most potent stimulators of CCK and GLP-1 release in human duodenal tissue, and may therefore be good dietary additives in weight management.
Safety and efficacy of long-term use of sodium oxybate for narcolepsy with cataplexy in routine clinical practice (2017)

Sodium oxybate provides a good clinical efficacy and acceptable safety profile in routine clinical practice for the treatment of patients suffering from narcolepsy with cataplexy. A quarter of patients experience SEs requiring withdrawal of the drug with older patients being more vulnerable to the more serious SEs.
Noninvasive monitoring of glucose concentration using differential absorption low-coherence interferometry based on rapid scanning optical delay line (2011)

A non-invasive method of detecting glucose concentration using differential absorption low-coherence interferometry (DALCI) based on rapid scanning optical delay line is presented. Two light sources, one centered within (1625 nm) a glucose absorption band, while the other outside (1310 nm) the glucose absorption band, are used in the experiment. The low-coherence interferometry (LCI) is employed to obtain the signals back-reflecting from the iris which carries the messages of material concentration in anterior chamber. Using rapid scanning optical delay line (RSOD) as the reference arm, we can detect the signals in a very short time. Therefore the glucose concentration can be monitored in real-time, which is very important for the detection in vivo. In our experiments, the cornea and aqueous humor can be treated as nearly non-scattering substance. The difference in the absorption coefficient is much larger than the difference in the scattering coefficient, so the influence of scattering can be neglected. By subtracting the algorithmic low-coherence interference signals of the two wavelengths, the absorption coefficient can be calculated which is proportional to glucose concentration. To reduce the speckle noise, a 30 variation of signals were used before the final calculation of the glucose concentration. The improvements of our experiment are also discussed in the article. The method has a potential application for noninvasive detection of glucose concentration in vivo and in real-time.
Neuronal cell differentiation of human neuroblastoma cells by retinoic acid plus herbimycin A. (1988)

We investigated the effect of retinoic acid (RA) and herbimycin A (herb-A) on cell growth, cell differentiation, and colony formation of human neuroblastoma cell lines. The neuroblastoma line SK-N-SH expressed both neuroblast and nonneuronal phenotypes, whereas its subclone SH-SY5Y and the Kelly cell line were predominantly neuroblastic. Both herb-A and RA, given alone, moderately reduced cell growth and colony formation of the neuroblastic cell lines. Growth curve analyses with SK-N-SH suggested that herb-A greatly reduced the number of initially growing cells, whereas RA slightly enhanced initial cell growth. Morphological changes were determined with the use of rhodaminephalloidin staining of actin. Retinoic acid caused an increase in the fraction of neuroblast cell in SK-N-SH, and conversely of nonneuronal cells in SH-SY5Y and Kelly cell lines. Both drugs also caused partial differentiation towards a neuronal phenotype, and herb-A induced selective lysis of nonneuronal cells of SK-N-SH. Because of their discrepant effects, RA (10 microM) and herb-A (236 nM) were tested in combination at a concentration that had only moderate effects when given alone. The combination further reduced cell growth and colony formation and dramatically enhanced differentiation towards a neuronal morphology. The Kelly cell line with amplified N-myc genome, which correlates with clinical progression of neuroblastoma, was also sensitive to RA plus herb-A. These results recommend the combination of RA and herb-A for differentiation therapy of neuroblastoma.
Isolation and characterization of a monoclonal antibody-resistant antigenic mutant of Toxoplasma gondii. (1982)

Several monoclonal antibodies against Toxoplasma gondii were parasiticidal in the presence of normal human serum as measured by reduction in plaque titer or in assays that detected lysis. One monoclonal antibody, G, was used to select a resistant mutant from a large population of chemically mutagenized wild-type parasites. This mutant retained the wild-type sensitivity to other monoclonal antibodies and to polyclonal antisera. A comparison of surface radioiodinated wild-type and mutant parasites by using one and two-dimensional electrophoresis showed that the mutant lacked a protein (or proteins) of approximate m.w. 22,000. An immunoprecipitation procedure using monoclonal antibody G yielded a protein(s) of this m.w. from surface radioiodinated wild-type T. gondii but not from surface radioiodinated mutant parasites.
Oncogenic role of clusterin overexpression in multistage colorectal tumorigenesis and progression (2005)

These data suggests that overexpression of cytoplasmic clusterin might be involved in the tumorigenesis and/or progression of CRCs. The anti-apoptotic function of cytoplasmic clusterin may be responsible, at least in part, for the development and biologically aggressive behavior of CRC.
Quercetin, Siamois 1 and siamois 2 induce apoptosis in human breast cancer MDA-MB-435 cells xenograft in vivo (2007)

We sought to investigate the apoptosis-inducing activities of quercetin, Siamois 1, and Siamois 2 against invasive estrogen-receptor negative MDA-MB 435 cells xenografted in athymic nude mice. This study clearly demonstrated that these compounds exhibited apoptosis-inducing activities in cell culture system. Quercetin (20 microg/mL), Siamois 1 (100 microg/mL), and Siamois 2 (200 microg/mL) can induce apoptotic cell death by 40 +/-5%, 44 +/- 14 %, and 31 +/- 13 %, respectively. Two-fold of IC50 of these compounds were clearly found to induce apoptosis in breast tumor tissue which can be determined by 99mTc-Annexin V scintigraphy and histological staining. This is the first report that the apoptosis-inducing effects of quercetin, Siamois 1 and Siamois 2 on the MDA-MB 435 cell in vitro were effectively extrapolated to the in vivo situation. These compounds might be considered as a simple dietary supplement and with further clinical investigation for their use as a nutrition-based intervention in breast cancer treatment.
HMG-I/Y Is a c-Jun/Activator Protein-1 Target Gene and Is Necessary for c-Jun–Induced Anchorage-Independent Growth in Rat1a Cells (2004)

The transcription complex activator protein-1 (AP-1) plays a role in a diverse number of cellular processes including proliferation, differentiation, and apoptosis. To identify AP-1-responsive target genes, we used a doxycycline-inducible c-Jun system in Rat1a cells. The HMG-I/Y chromatin binding protein was found to be up-regulated by c-Jun. Following induction of c-Jun expression, Rat1a cells under nonadherent growth conditions have sustained HMG-I/Y mRNA expression and 2-fold higher protein than uninduced cells. HMG-I/Y promoter reporter assays show that HMG-I/Y promoter activity increases in the presence of c-Jun expression, and gel mobility shift assays demonstrate that induced c-Jun binds to an AP-1 consensus site at position -1,091 in the HMG-I/Y promoter. Suppression of HMG-I/Y expression by its antisense sequence significantly reduces the ability of c-Jun-overexpressing Rat1a cells to grow in an anchorage-independent fashion. HMG-I/Y transforms Rat1a cells (although the colonies are smaller than that observed for the cells overexpressing c-Jun). Taken together, these results suggest that HMG-I/Y is a direct transcriptional target of c-Jun necessary for c-Jun-induced anchorage-independent growth in Rat1a cells.
Ribozyme-Mediated Inhibition of Caspase-3 Protects Cerebellar Granule Cells from Apoptosis Induced by Serum–Potassium Deprivation (2000)

Apoptosis is an important mechanism of physiological and pathological cell death. It is regulated by several gene products, including caspases and the bcl-2-like proteins, whose roles have been demonstrated in numerous systems. One of these is a model of cerebellar granule cells (CGCs) in which apoptosis is induced by acute removal of serum and depolarizing concentrations of potassium. Previous work by several authors showed that benzyloxycarbonyl-DEVD-fluoromethylketone, a somewhat selective caspase inhibitor, significantly protected CGCs from apoptosis; however, because this molecule targets multiple caspases, it is not known whether a single caspase is primarily responsible for effecting cell death in this model. We attempted to answer this question by cotransfecting CGCs with green fluorescent protein reporter and a hammerhead ribozyme directed against caspase-3 mRNA. Maximal protection by this ribozyme was observed after 24 hr of deprivation, at which time apoptosis was 18 +/- 0.7% compared with 32 +/- 2% in control cells. Significant protection was also observed with human inhibitor of apoptosis (IAP)-like protein-X-linked IAP, a specific inhibitor of caspase-3, -7, and -9, and with p35, a general caspase inhibitor. Overexpression of bcl-2 produced almost complete protection from apoptosis after 24 hr of serum-K(+) deprivation (5 +/- 2 vs 44 +/- 2% in control cells). These results confirm that caspases play an important role in CGC apoptosis and indicate that caspase-3 itself is a significant mediator of this process.
Sex Preselection in Swine: Altered Sex Ratios in Offspring following Surgical Insemination of Flow Sorted X‐ and Y‐Bearing Sperm (1991)

Contents: Flow cytometric sorting of X and Y chromosome‐bearing sperm into separate populations, followed by surgical insemination into the isthmus of the oviduct of mature gilts, produced litters with phenotypic sex ratios skewed in the direction of male or female according to the predicted sex of the sperm population inseminated. The skewing of the sex ratio of the offspring was predicted from flow cytometric DNA reanalysis of flow sorted sperm populations. Gilts inseminated with intact, viable flow‐sorted X‐bearing sperm produced litters of off spring that were 74% female (P &lt; .01). Gilts inseminated with intact, viable flow‐sorted Y‐bearing sperm gave off spring that were 68% male (P &lt; .04). These results validate the use of DNA as a marker for pre‐selecting the sex of offspring when used in conjunction with flow cytometric sorting of sperm .
ImageNet classification with deep convolutional neural networks (2017)

We trained a large, deep convolutional neural network to classify the 1.2 million high-resolution images in the ImageNet LSVRC-2010 contest into the 1000 different classes. On the test data, we achieved top-1 and top-5 error rates of 37.5% and 17.0%, respectively, which is considerably better than the previous state-of-the-art. The neural network, which has 60 million parameters and 650,000 neurons, consists of five convolutional layers, some of which are followed by max-pooling layers, and three fully connected layers with a final 1000-way softmax. To make training faster, we used non-saturating neurons and a very efficient GPU implementation of the convolution operation. To reduce overfitting in the fully connected layers we employed a recently developed regularization method called "dropout" that proved to be very effective. We also entered a variant of this model in the ILSVRC-2012 competition and achieved a winning top-5 test error rate of 15.3%, compared to 26.2% achieved by the second-best entry.
Multiband Sierpinskl fractal patch antenna (2002)

The multiband behavior of the Sierpinski patch antenna is described, and a new technique to improve the multiband behavior from the point of view of the radiation patterns is introduced. The technique suppresses the effects of the high order modes and a patch antenna with similar radiation patterns can be designed. Once the high order mode has been suppressed for the second band, the next step is to try eliminate it for the third and fourth band breaking the appropriate junctions.
Customizable parallel execution of scientific stream queries (2005)

Scientific applications require processing high-volume on-line streams of numerical data from instruments and simulations. We present an extensible stream database system that allows scalable and flexible continuous queries on such streams. Application dependent streams and query functions are defined through an Object-Relational model. Distributed execution plans for continuous queries are described as high-level data flow distribution templates. Using a generic template we define two partitioning strategies for scalable parallel execution of expensive stream queries: window split and window distribute. Window split provides operators for customized parallel execution of query functions whose complexity depends on size of the data units on which they are applied. It reduces the size of stream data units using application dependent functions as parameters. By contrast, window distribute provides operators for customized distribution of entire data units without reducing their size. We evaluated these strategies for a typical high volume scientific stream application and show that window split is favorable when computational resources are limited, while window distribute is better when there are sufficient resources.
Monoamine Oxidase Inhibition for Tobacco Pharmacotherapy (2007)

Tobacco addiction is the most significant preventable cause of morbidity and mortality in the Western world, with >430,000 deaths annually from tobacco-related diseases being reported in the United States. Although effective treatments are available for cessation of smoking (e.g., nicotine replacement therapies, sustained-release bupropion and varenicline), they do not work for all smokers. Therefore the development of more effective medications for treating tobacco dependence, based on novel mechanisms, is a high priority. This article reviews the links between smoking and monoamine oxidase (MAO) inhibition, which could lead to the development of novel pharmacotherapies to treat tobacco dependence.
Dog coronary artery adenosine receptor. Structure of the N6-aryl subregion (1986)

Previous structure-coronary vasoactivity correlations of the N6-alkyladenosine analogues of N6-[(R)-1-phenyl-2-propyl]adenosine, 1, support the hypothesis that the coronary artery A2 adenosine receptor contains an N6 region of specialized structure. The part of this receptor region that binds the 2-propyl moiety of 1 determines stereoselectivity and contributes to coronary vasoactivity. The present study uses 92 adenosine analogues containing an aryl group in the N6 substituent to test the hypothesis that the N6 receptor region contains an aryl subregion that binds the phenyl moiety of 1 and thereby contributes to its coronary vasoactivity. N6-Aralkyladenosines are often more potent than their alkyl congeners. Two methylene residues seem to provide optimum separation of the aryl group from N6. Among adenosines with semirigid N6 substituents, N6-[(1R,2S)-trans-2-phenylcyclohexyl]adenosine was uniquely active, evidence that when 1 occupies the receptor, the axis of the propyl C-1 to phenyl C-1 bond is nearly in the plane described by N6 and propyl C-1 and C-2. The torsion angle around this bond is unknown. Replacing the phenyl group of N6-2-phenethyladenosine with a thienyl or a 3-pyridyl group raises activity. The structure-activity relationships of the N6-(arylethyl)-, the N6-(arylmethyl)-, and the N6-phenyladenosines differ strinkingly from each other. Taken together, such results support the idea that the N6 region of the dog coronary artery A2 adenosine receptor includes an aryl subregion.