gebhart/patrepeval huggingface dataset:
Inhibitory effects of certain enantiomeric cannabinoids in the mouse vas deferens and the myenteric plexus preparation of guinea‐pig small intestine (1992)

1. The psychoactive cannabinoids (-)-delta 9-tetrahydrocannabinol ((-)-delta 9-THC) and the 1,1-dimethyl-heptyl homologue of (-)-11-hydroxy-delta 8-tetrahydrocannabinol ((-)-DMH) both inhibited electrically-evoked contractions of the mouse isolated vas deferens and the myenteric plexus-longitudinal muscle preparation of the guinea-pig small intestine. 2. Concentrations of (-)-delta 9-THC and (-)-DMH that decreased twitch heights by 50% were 6.3 and 0.15 nM respectively in the mouse vas deferens and 60 nM and 1.4 nM respectively in the myenteric plexus preparation. (-)-DMH was about 40 times more potent than (-)-delta 9-THC in both preparations, supporting the notion that their mode of action in each tissue is the same. 3. The psychically inactive cannabinoid, (+)-DMH, had no inhibitory effect in the mouse vas deferens at a concentration of 30 nM, showing it to be at least 1000 times less potent than (-)-DMH. In the myenteric plexus preparation, (+)-DMH was about 500 times less potent than its (-)-enantiomer. 4. The inhibitory effects of sub-maximal concentrations of (-)-delta 9-THC were not attenuated by 300 nM naloxone. 5. The findings that (-)-delta 9-THC and (-)-DMH are highly potent as inhibitors of the twitch response of the mouse vas deferens and guinea-pig myenteric plexus preparation and that DMH shows considerable stereoselectivity suggest that the inhibitory effects of cannabinoids in these preparations are mediated by cannabinoid receptors.
Electrical properties of GeSi surface- and buried-channel p-MOSFETs fabricated by Ge implantation (1996)

The electrical properties of surface- and buried-channel p-MOSFETs containing strained GeSi heterostructures synthesized by high-dose Ge implantation and solid phase epitaxial growth have been investigated. Compared with Si control devices on the same chips, GeSi transistors exhibited improved performance: the channel hole mobility and linear transconductance was up to 18% higher for surface-channel GeSi transistors, and up to 12% higher for buried-channel GeSi p-MOSFETs, than for equivalent Si devices. Ion-beam synthesis of GeSi strained layers therefore offers an attractive means for realising improved device performance in conventional Si device structures.
A new, non-destructive method for analysis of clinical samples with FT-IR microspectroscopy. Breast cancer tissue as an example. (1998)

A new method for infrared analysis of tissues and cells is presented. The method is based on Fourier transform infrared microspectroscopy coupled with attenuated total reflectance. The technique allows spectroscopic measurements on the same samples used by pathologists for histopathological evaluation, e.g. stained samples on plain glass slides. Since the same specimen can be used as for histopathology, the method does not require sample preparation or modification. Significantly, the sample is not damaged. Glass absorbs in the infrared and thus has not been used previously in infrared analysis of tissues and cells. Conventional infrared techniques utilize expensive substrates, such as BaF2 windows and gold coated slides which do not absorb infrared radiation. However, these measurements require special preparation and result in the destruction of the sample. Breast cancer tissues were examined to demonstrate the feasibility and reproducibility of the new method. Linear discriminant analysis was used to discriminate and classify three types of cells: benign, atypical hyperplasia and malignant. It was demonstrated that benign vs. malignant cells were discriminated with 100% accuracy, benign vs. atypical hyperplasia were discriminated with 100% accuracy and malignant vs. atypical hyperplasia were discriminated with an accuracy of 90% and higher.
Reflections on the biology of embryonic stem (ES) cells (1997)

Remarkably little is known about mammalian embryonic stem (ES) cells despite their very widespread use in studies on gene disruption and transgenesis. As yet, it is only in the mouse that lines of ES cells which retain the ability to form gametes following reintroduction into the early conceptus have been obtained. Even in this species, most strains have so far proved refractory to the derivation of such cell lines. Apart from persisting ignorance as to how the various procedures that have been claimed to improve success actually do so, even the tissue of origin of ES remains uncertain. Furthermore, it is doubtful whether retention of pluripotency or expression of so-called "stem cell" marker molecules provide an adequate basis for classifying cells as genuine ES cells. This is because epiblast cells, their presumed precursors, lose the capacity to colonize the preimplantation conceptus well before they become restricted in the types of cell they can form or cease to express such marker molecules. In addition, it has yet to be established whether heterogeneity of cells within individual ES cell lines arises entirely during culture or is at least partly attributable to lack of homogeneity among their precursors. Finally, it has yet to be explained why ES chimeras evidently differ from those obtained by combining cells from different conceptuses in showing greater variation between tissues in the level of chimerism.
A small-cell lung cancer genome with complex signatures of tobacco exposure (2009)

Cancer is driven by mutation. Worldwide, tobacco smoking is the principal lifestyle exposure that causes cancer, exerting carcinogenicity through >60 chemicals that bind and mutate DNA. Using massively parallel sequencing technology, we sequenced a small-cell lung cancer cell line, NCI-H209, to explore the mutational burden associated with tobacco smoking. A total of 22,910 somatic substitutions were identified, including 134 in coding exons. Multiple mutation signatures testify to the cocktail of carcinogens in tobacco smoke and their proclivities for particular bases and surrounding sequence context. Effects of transcription-coupled repair and a second, more general, expression-linked repair pathway were evident. We identified a tandem duplication that duplicates exons 3-8 of CHD7 in frame, and another two lines carrying PVT1-CHD7 fusion genes, indicating that CHD7 may be recurrently rearranged in this disease. These findings illustrate the potential for next-generation sequencing to provide unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer.
CELLULAR FUNCTIONS REGULATED BY SRC FAMILY KINASES (1997)

Src family protein tyrosine kinases are activated following engagement of many different classes of cellular receptors and participate in signaling pathways that control a diverse spectrum of receptor-induced biological activities. While several of these kinases have evolved to play distinct roles in specific receptor pathways, there is considerable redundancy in the functions of these kinases, both with respect to the receptor pathways that activate these kinases and the downstream effectors that mediate their biological activities. This chapter reviews the evidence implicating Src family kinases in specific receptor pathways and describes the mechanisms leading to their activation, the targets that interact with these kinases, and the biological events that they regulate.
Exploiting evidence from unstructured data to enhance master data management (2012)

Master data management (MDM) integrates data from multiple structured data sources and builds a consolidated 360-degree view of business entities such as customers and products. Today's MDM systems are not prepared to integrate information from unstructured data sources, such as news reports, emails, call-center transcripts, and chat logs. However, those unstructured data sources may contain valuable information about the same entities known to MDM from the structured data sources. Integrating information from unstructured data into MDM is challenging as textual references to existing MDM entities are often incomplete and imprecise and the additional entity information extracted from text should not impact the trustworthiness of MDM data. In this paper, we present an architecture for making MDM text-aware and showcase its implementation as IBM Info-Sphere MDM Extension for Unstructured Text Correlation, an add-on to IBM InfoSphere Master Data Management Standard Edition. We highlight how MDM benefits from additional evidence found in documents when doing entity resolution and relationship discovery. We experimentally demonstrate the feasibility of integrating information from unstructured data sources into MDM.
Purification and Characterization of an Extracellular Dextransucrase from Pediococcus pentosaceus Isolated from the Soil of North East India (2011)

The extracellular dextransucrase produced from Pediococcus pentosaceus, a new isolate from the soil in Assam, India, was purified and characterized.The enzyme activity of cell-free supernatant was 3.4 U/mL and specific activity was 0.6 U/mg.The crude enzyme was purified by a single-step fractionation using polyethylene glycols of different molecular mass.The specific activity achieved was 18 U/mg with 31-fold purification by PEG 400 and 26 U/mg with 45-fold purification by PEG 1500.The molecular mass of dextransucrase determined by non-denaturing SDS-PAGE was approx.180 kDa.The dextran formation activity of the enzyme was confirmed by activity staining.Optimum conditions for dextransucrase activity were: pH=5.4,reaction temperature 30 C, 5 % sucrose and 20 mM sodium acetate buffer.A concentration of 1 mM MgCl 2 and 6 mM CaCl 2 enhanced dextransucrase activity by 5 and 150 %, respectively.The chaotropic agent urea (7 M) and chelating agent EDTA (1 mM) resulted in the residual enzyme activity of 98 and 80 %, respectively.The organic solvents such as ethanol (50 %), DMSO (90 %), acetone (50 %) and acetonitrile (20 %) decreased the dextransucrase activity by 80, 91, 94 and 80 %, respectively.
Composition and properties of ZnS thin films prepared by chemical bath deposition from acidic and basic solutions (2005)

Zinc sulfide thin films were prepared by chemical bath deposition (CBD) on soda lime glass, silicon and gallium phosphide substrates using an acidic (acetic acid-thioacetamide), and ammonia (thiourea or thioacetamide) baths. The thickness of the films varied from a few nm to 100 nm. Films deposited using the acidic bath showed a smaller concentration of Zn-O bonds and are much closer to ZnS stoichiometry, as it was found by X-ray photoelectron spectroscopy and wavelength-dispersive X-ray fluorescence spectroscopies. X-ray diffraction patterns prove crystallinity of as deposited films from the acidic bath, which crystallize in the cubic modification. The optical band-gap energy was determined to be 3.64 eV from the best-fit of spectroscopic ellipsometry measurements. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
Integrin Mediated Fibronectin Matrix Assembly. (1996)

フィブロネクチン (Fn) マトリクスアセンブリーは動的な細胞現象であるが、その過程で可溶性の二量体Fnは会合してジスルフィド結合によって安定化された不溶性の線維性高分子マトリクスを形成する。FnがマトリクスアセンブリーするためにはFnに特異的に結合するインテグリンが必要である。Fnマトリクスアセンブリーに関与するインテグリンとしてはα5β1、αIIbβ3、αVβ3などが同定されている。細胞はこれらインテグリンの細胞表層発現量を調節したり。あるいはFnや細胞骨格系タンパク質とインテグリンとの結合を制御することによって、Fnマトリクスアセンブリーをコントロールしている。細胞外で生じるFnマトリクスアセンブリーが、細胞表層のインテグリンや細胞内の情報伝達分子によってどのように制御されるかを明らかにすることが今後の研究課題となろう。
[Anti-hyperlipidemic agents]. (2002)

There are several drugs for hyperlipidemia except for statin and fibrate. Resin is a commonly used drug for hypercholesterolemia and is known to very useful for the prevention of coronary heart disease(CHD). Probucol is also used for hypercholesterolemia and recently is known that it prevent the restenosis of the coronary artery after PTCA. Nicotinic acid is used for hypertriglyceridemia and hypercholesterolemia, both. It is also known to very useful for the prevention of CHD. Eicosapentaenoic acid is effective for hypertriglyceridemia and also shows an inhibition of platelets aggregation. These drugs as well as statin and fibrate are used in combination with each other for severe hyperlipidemia.
The Arthus Reaction in Rodents: Species-Specific Requirement of Complement (2000)

We induced reverse passive Arthus (RPA) reactions in the skin of rodents and found that the contribution of complement to immune complex-mediated inflammation is species specific. Complement was found to be necessary in rats and guinea pigs but not in C57BL/6J mice. In rats, within 4 h after initiation of an RPA reaction, serum alternative pathway hemolytic titers decreased significantly below basal levels, whereas classical pathway titers were unchanged. Thus the dermal reaction proceeds coincident with systemic activation of complement. The serine protease inhibitor BCX 1470, which blocks the esterolytic and hemolytic activities of the complement enzymes Cls and factor D in vitro, also blocked development of RPA-induced edema in the rat. These data support the proposal that complement-mediated processes are of major importance in the Arthus reaction in rats and guinea pigs, and suggest that BCX 1470 will be useful as an anti-inflammatory agent in diseases where complement activation is known to be detrimental.
Electrooptic phase modulation of stretched 250-fs pulses for suppression of third-order fiber dispersion in transmission (1999)

Optical pulse distortion due to third-order dispersion (TOD) in linear fiber transmission of 250-fs pulses at 5 GHz over 600 m is reduced by applying electrooptic phase modulation (EOPM) from a LiNbO/sub 3/ device. Initial propagation in dispersion-compensating fiber cancels the second-order dispersion of the fiber-link and also linearly chirps the pulses to a stretched width of 47 ps, which enables TOD compensation by the following 5-GHz EOPM. Good agreement between experimental and analytical results is shown. Comparable transmission improvement for the 250-fs pulses is achieved up to a maximum repetition rate of 6 GHz, limited by the RF amplifier bandwidth.
Heteroaryl-Substituted Naphthalenes and Structurally Modified Derivatives:  Selective Inhibitors of CYP11B2 for the Treatment of Congestive Heart Failure and Myocardial Fibrosis (2005)

Recently we proposed inhibition of aldosterone synthase (CYP11B2) as a novel strategy for the treatment of congestive heart failure and myocardial fibrosis. In this study the synthesis and biological evaluation of heteroaryl-substituted naphthalenes and quinolines (1-31) is described. Key step for the preparation of the compounds was a Suzuki cross-coupling. Activity of the compounds was determined in vitro using human CYP11B2 and selectivity was evaluated toward the human steroidogenic enzymes CYP11B1, CYP19, and CYP17. A large number of highly active and selective inhibitors of CYP11B2 was identified. The most active inhibitor was the 6-cyano compound 8 (IC50 = 3 nM) showing a competitive type of inhibition (K(i) value = 1.9 nM). The 6-ethoxy derivative 5 was found to be the most selective CYP11B2 inhibitor (IC50 = 12 nM; K(i) value = 8 nM; CYP11B1 IC50 = 5419 nM; selectivity factor = 451), showing no inhibition of human CYP3A4 (50 nM) and CYP2D6 (20 nM). Docking and molecular dynamics studies using our homology modeled CYP11B2 structure with selected compounds were performed. Caco-2 cell experiments revealed a large number of medium and highly permeable compounds and metabolic studies with 2 using rat liver microsomes showed sufficient stability.
Assessing circuit-level hot-carrier reliability (1998)

The major factors that cumulatively determine circuit-level hot-carrier reliability are defined and characterized in this paper. The inherent inverse relationship between lifetime-underestimation/criteria-overspecification and the amount of known device/circuit information is explored. Lifetime-underestimation/criteria-overspecification is shown to depend quite strongly on the particular "worst-case" approximations used.
Terminal neuroendocrine differentiation of human prostate carcinoma cells in response to increased intracellular cyclic AMP. (1994)

Recent clinicopathologic studies have shown that many prostatic adenocarcinomas express focal neuroendocrine differentiation and that neuroendocrine differentiation is most apparent in advanced anaplastic tumors. While studying growth-regulatory signal transduction events in human prostate carcinoma cell lines, we found that in two of four cell lines, the androgen-sensitive line LNCaP and the highly metastatic androgen-independent line PC-3-M, elevation of cAMP through addition of cAMP analogues or phosphodiesterase inhibitors induced a markedly neuronal morphology. Also in LNCaP cells ultrastructural analysis showed that cAMP induced the appearance of neurosecretory cell-like dense-core granules. Phenotypic analysis of untreated LNCaP and PC-3-M cells showed that both cell lines express markers of the neural crest including S-100, chromogranin A, pp60c-src, and neuron-specific enolase as well as the epithelial marker KS1/4 and stage-specific embryonic antigen 4. In PC-3-M cells, cAMP markedly elevated neuron-specific enolase protein and caused an increase in the specific activity of the neuroendocrine marker pp60c-src, and in both cell lines expression of KS1/4 and stage-specific embryonic antigen 4 was down-regulated. In addition to effects on lineage markers, cAMP treatment induced G1 synchronization, growth arrest, and loss of clonogenicity, indicating terminal differentiation. Our data provide direct evidence of plasticity in the lineage commitment of adenocarcinoma of the prostate. We have shown that cell-permeant cAMP analogues can induce terminal differentiation, suggesting that hydrolysis-resistant cyclic nucleotides may present an additional approach to the treatment of advanced prostate cancer.
Safety and Efficacy of nab-Paclitaxel in the Treatment of Patients with Breast Cancer (2011)

Taxanes are highly active chemotherapeutic agents in the treatment of early-stage and metastatic breast cancer. Novel formulations have been developed to improve efficacy and decrease toxicity associated with these cytotoxic agents. nab-paclitaxel is a solvent free, albumin-bound 130-nanometer particle formulation of paclitaxel (Abraxane(®), Abraxis Bioscience), which was developed to avoid toxicities of the Cremophor vehicle used in solvent-based paclitaxel. In a phase III clinical trial, nab-paclitaxel demonstrated higher response rates, better safety and side-effect profile compared to conventional paclitaxel, and improved survival in patients receiving it as second line therapy. Higher doses can be administered over a shorter infusion time without the need for special infusion sets or pre-medications. It is now approved in the US for treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant therapy, where prior therapy included an anthracycline. Recently, several phase II studies have suggested a role for nab-paclitaxel as a single agent and in combination with other agents for first-line treatment of metastatic breast cancer.
Enhancing the catalytic repertoire of nucleic acids: a systematic study of linker length and rigidity (2001)

The incorporation of potentially catalytic groups in DNA is of interest for the in vitro selection of novel deoxyribozymes. A series of 10 C5-modified analogues of 2'-deoxyuridine triphosphate have been synthesised that possess side chains of differing flexibility and bearing a primary amino or imidazole functionality. For each series of nucleotide analogues differing degrees of flexibility of the C5 side chain was achieved through the use of alkynyl, alkenyl and alkyl moieties. The imidazole function was conjugated to these C5-amino-modified nucleotides using either imidazole 4-acetic acid or imidazole 4-acrylic acid (urocanic acid). The substrate properties of the nucleotides (fully replacing dTTP) with TAQ polymerase during PCR have been investigated in order to evaluate their potential applications for in vitro selection experiments. 5-(3-Aminopropynyl)dUTP and 5-(E-3-aminopropenyl)dUTP and their imidazole 4-acetic acid- and urocanic acid-modified conjugates were found to be substrates. In contrast, C5-amino-modified dUTPs with alkane or Z-alkene linkers and their corresponding conjugates were not substrates. The incorporation of these analogues during PCR has been confirmed by inhibition of restriction enzyme digestion using XBAI and by mass spectrometry of the PCR products.
Reduction of β-Amyloid Levels by Novel Protein Kinase Cϵ Activators (2009)

Isoform-specific protein kinase C (PKC) activators may be useful as therapeutic agents for the treatment of Alzheimer disease. Three new epsilon-specific PKC activators, made by cyclopropanation of polyunsaturated fatty acids, have been developed. These activators, AA-CP4, EPA-CP5, and DHA-CP6, activate PKCepsilon in a dose-dependent manner. Unlike PKC activators that bind to the 1,2-diacylglycerol-binding site, such as bryostatin and phorbol esters, which produce prolonged down-regulation, the new activators produced sustained activation of PKC. When applied to cells expressing human APPSwe/PS1delta, which produce large quantities of beta-amyloid peptide (Abeta), DCP-LA and DHA-CP6 reduced the intracellular and secreted levels of Abeta by 60-70%. In contrast to the marked activation of alpha-secretase produced by PKC activators in fibroblasts, the PKC activators produced only a moderate and transient activation of alpha-secretase in neuronal cells. However, they activated endothelin-converting enzyme to 180% of control levels, suggesting that the Abeta-lowering ability of these PKCepsilon activators is caused by increasing the rate of Abeta degradation by endothelin-converting enzyme and not by activating nonamyloidogenic amyloid precursor protein metabolism.
Mutagenesis of Specific Amino Acids Converts Carnitine Acetyltransferase into Carnitine Palmitoyltransferase (2006)

Carnitine acyltransferases catalyze the exchange of acyl groups between carnitine and CoA. The members of the family can be classified on the basis of their acyl-CoA selectivity. Carnitine acetyltransferases (CrATs) are very active toward short-chain acyl-CoAs but not toward medium- or long-chain acyl-CoAs. Previously, we identified an amino acid residue (Met(564) in rat CrAT) that was critical to fatty acyl-chain-length specificity. M564G-mutated CrAT behaved as if its natural substrates were medium-chain acyl-CoAs, similar to that of carnitine octanoyltransferase (COT). To extend the specificity of rat CrAT to other substrates, we have performed new mutations. Using in silico molecular modeling procedures, we have now identified a second putative amino acid involved in acyl-CoA specificity (Asp(356) in rat CrAT). The double CrAT mutant D356A/M564G showed 6-fold higher activity toward palmitoyl-CoA than that of the single CrAT mutant M564G and a new activity toward stearoyl-CoA. We show that by performing two amino acid replacements a CrAT can be converted into a pseudo carnitine palmitoyltransferase (CPT) in terms of substrate specificity. To change CrAT specificity from carnitine to choline, we also prepared a mutant CrAT that incorporates four amino acid substitutions (A106M/T465V/T467N/R518N). The quadruple mutant shifted the catalytic discrimination between l-carnitine and choline in favor of the latter substrate and showed a 9-fold increase in catalytic efficiency toward choline compared with that of the wild-type. Molecular in silico docking supports kinetic data for the positioning of substrates in the catalytic site of CrAT mutants.