gebhart/patrepeval huggingface dataset:
Cysteine tagging for MS‐based proteomics (2010)

Amino acid-tagging strategies are widespread in proteomics. Because of the central role of mass spectrometry (MS) as a detection technique in protein sciences, the term "mass tagging" was coined to describe the attachment of a label, which serves MS analysis and/or adds analytical value to the measurements. These so-called mass tags can be used for separation, enrichment, detection, and quantitation of peptides and proteins. In this context, cysteine is a frequent target for modifications because the thiol function can react specifically by nucleophilic substitution or addition. Furthermore, cysteines present natural modifications of biological importance and a low occurrence in the proteome that justify the development of strategies to specifically target them in peptides or proteins. In the present review, the mass-tagging methods directed to cysteine residues are comprehensively discussed, and the advantages and drawbacks of these strategies are addressed. Some concrete applications are given to underline the relevance of cysteine-tagging techniques for MS-based proteomics.
Fuzzy Logic: Intelligence, Control, and Information (1998)

1. Introduction. 2. Basic Concepts of Fuzzy Logic. 3. Fuzzy Sets. 4. Fuzzy Relations, Fuzzy Graphs, and Fuzzy Arithmetic. 5. Fuzzy If-Then Rules. 6. Fuzzy Implications and Approximate Reasoning. 7. Fuzzy Logic and Probability Theory. 8. Fuzzy Logic in Control Engineering. 9. Hierarchical Intelligent Control. 10. Analytical Issues in Fuzzy Logic Control. 11. Fuzzy Logic and Artificial Intelligence. 12. Fuzzy Logic in Database Management and Information Systems. 13. Fuzzy Logic in Pattern Recognition. 14. Fuzzy Model Identification. 15.Advanced Topics of Fuzzy Model Identification. 16.Neuro-Fuzzy Systems. 17. Genetic Algorithms and Fuzzy Logic. References. Index.
5‐Cyano‐6‐aryluracil and 2‐thiouracil derivatives as potential chemotherapeutic agents. IV (1984)

Abstract A series of 5‐cyano‐6‐aryluracils and 2‐thiouracils 1a‐h has been prepared and alkylated to 1,3‐dialkyluracils 2a‐d and 2‐alkylthiouracils, 3, 4 and 6 , by electrophilic substitution with alkyl halides. Reaction of 1b with dibromoethane and 1,3‐dibromopropane gave the corresponding bicyclic products, 7‐aryl‐6‐cyano‐2,3‐dihydrothiazolo[3,2‐ a ]pyrimidin‐5‐ones 5a,b and 8‐aryl‐7‐cyano‐3,4‐dihydro‐2 H ‐pyrimido[2,3‐ b ][1,3]thiazin‐6‐ones 5c‐g . Nucleophilic substitution on 6 with hydrazine led to 7 which on refluxing with formic acid gave 5‐aryl‐6‐cyano‐8‐methyl‐ s ‐triazolo[3,4‐ b ]pyrimidin‐7‐ones ( 9 ), while with acetic and propionic acids only 2‐acylhydrazino‐3‐methyl‐4‐oxo‐5‐cyano‐6‐arylpyrimidines 8a,b were isolated. The hydrazine 7 undergoes cyclization with acetylacetone and methyl dimethylmercaptoacrylate providing 2‐(pyrazol‐1‐yl)‐3‐methyl‐4‐oxo‐5‐cyano‐6‐substituted pyrimidines 10 , and 11 . Some of the compounds were screened for antibacterial‐, antifungal‐ and antiviral activities and a few of them showed significant chemotherapeutical activities.
Deep Learning Inference Service at Microsoft (2019)

This paper introduces the Deep Learning Inference Service, an online production service at Microsoft for ultra-low-latency deep neural network model inference. We present the system architecture and deep dive into core concepts such as intelligent model placement, heterogeneous resource management, resource isolation, and efficient routing. We also present production scale and performance numbers.
Ultra-compact 32 × 32 strictly-non-blocking Si-wire optical switch with fan-out LGA interposer (2015)

We demonstrate a 32 × 32 path-independent-insertion-loss optical path switch that integrates 1024 thermooptic Mach-Zehnder switches and 961 intersections on a small, 11 × 25 mm2 die. The switch is fabricated on a 300-mm-diameter silicon-on-insulator wafer by a complementary metal-oxide semiconductor-compatible process with advanced ArF immersion lithography. For reliable electrical packaging, the switch chip is flip-chip bonded to a ceramic interposer that arranges the electrodes in a 0.5-mm pitch land grid array. The on-chip loss is measured to be 15.8 ± 1.0 dB, and successful switching is demonstrated for digital-coherent 43-Gb/s QPSK signals. The total crosstalk of the switch is estimated to be less than -20 dB at the center wavelength of 1545 nm. The bandwidth narrowing caused by dimensional errors that arise during fabrication is discussed.
DNA Chip Technology in Brain Banks: Confronting a Degrading World (2004)

DNA microarray technology is based on the principle of hybridization between 2 complementary strands of nucleic acids, one being fixed into a solid membrane, the other being the sample to analyze. This has resulted in a very powerful method to examine differential gene expression between samples, and has been widely used in the study of tumors. The application of DNA microarray technology to the study of the nervous system has to consider several properties of the nervous tissue: composition of various neuronal types, as well as astrocytes, oligodendrocytes, and microglia; regional and area differences; developmental and age-dependent variations; and functional and pathological status. Moreover, human samples are usually obtained postmortem following variable agonal periods and postmortem delays between death and tissue preservation, which are accompanied by variable RNA degradation. Yet human postmortem nervous tissue stored in brain banks offers a unique opportunity to facilitate material for the study of diseases of the nervous system and to gain direct understanding on the mechanisms of disease. This review analyzes the application of DNA microarray technology to current practice using brain-banked tissues in order to recognize and minimize sub-optimal processing of brain samples and to correct pitfalls due to inadequate procedures. Also discussed are RNA preservation and RNA degradation effects on expression pattern assessments, analysis of individual versus pooled samples, array normalization, types of DNA chip platforms, whole genomic analysis versus specialized chips, and microgenomics. Minimizing RNA degradation and improving detection of resistant RNA in postmortem brain has been considered in detail in order to improve the efficiency and reliability of DNA microarray technology employed in the study of human postmortem nervous tissue.
Cholinoceptive and cholinergic properties of cardiomyocytes involving an amplification mechanism for vagal efferent effects in sparsely innervated ventricular myocardium (2009)

Our recent studies have shown that, as indicated by vagal stimulation, an acetylcholinesterase inhibitor donepezil, an anti-Alzheimer's disease drug, prevents progression of heart failure in rats with myocardial infarction, and activates a common cell survival signal shared by acetylcholine (ACh) in vitro. On the basis of this and evidence that vagal innervation is extremely poor in the left ventricle, we assessed the hypothesis that ACh is produced by cardiomyocytes, which promotes its synthesis via a positive feedback mechanism. Rat cardiomyocytes expressed choline acetyltransferase (ChAT) in the cytoplasm and vesicular acetylcholine transporter with the vesicular structure identified by immunogold electron microscopy, suggesting that cardiomyocytes possess components for ACh synthesis. Intracellular ACh in rat cardiomyocytes was identified with physostigmine or donepezil. However, with atropine, the basal ACh content was reduced. In response to exogenous ACh or pilocarpine, cardiomyocytes increased the transcriptional activity of the ChAT gene through a muscarinic receptor and ChAT protein expression, and, finally, the intracellular ACh level was upregulated by pilocarpine. Knockdown of ChAT by small interfering RNA accelerated cellular energy metabolism, which is suppressed by ACh. Although physostigmine had a minimal effect on the ChAT promoter activity by inhibiting acetylcholinesterase, donepezil resulted in elevation of the activity, protein expression and intracellular ACh level even in the presence of sufficient physostigmine. Orally administered donepezil in mice increased the ChAT promoter activity in a reporter gene-transferred quadriceps femoris muscle and the amount of cardiac ChAT protein. These findings suggest that cardiomyocytes possess an ACh synthesis system, which is positively modulated by cholinergic stimuli. Such an amplification system in cardiomyocytes may contribute to the beneficial effects of vagal stimulation on the ventricles.
Horseradish Peroxidase-Catalyzed Polymerization of Cardanol in the Presence of Redox Mediators (2003)

Horseradish peroxidase-catalyzed polymerization of cardanol in aqueous organic solvent was investigated in the presence of a redox mediator. Cardanol is a phenol derivative from a renewable resource mainly having a C15 unsaturated hydrocarbon chain with mostly 1-3 double bonds at a meta position. Unlike soybean peroxidase (SBP), it has been shown that horseradish peroxidase (HRP) is not able to perform oxidative polymerization of phenol derivatives having a bulky meta substituent such as cardanol. For the first time, redox mediators have been applied to enable horseradish peroxidase to polymerize cardanol. Veratryl alcohol, N-ethyl phenothiazine, and phenothiazine-10-propionic acid were tested as a mediator. It is surprising that the horseradish peroxidase-catalyzed polymerization of cardanol took place in the presence of N-ethyl phenothiazine or phenothiazine-10-propionic acid. However, veratryl alcohol showed no effect. FT-IR and GPC analysis of the product revealed that the structure and properties of polycardanol formed by HRP with a mediator were similar to those by SBP. This is the first work to apply a redox mediator to enzyme-catalyzed oxidative polymerization. Our new finding that oxidative polymerization of a poor substrate, which the enzyme is not active with, can take place in the presence of an appropriate mediator will present more opportunities for the application of enzyme-catalyzed polymerization.
EPIDEMIOLOGY OF GENITAL HUMAN PAPILLOMAVIRUS INFECTION (1988)

Recent clinical research has suggested a link between specific human papillomavirus types and the development of cancers of the genital tract and anus; however, supportive epidemiologic data are not well developed. In both the US and the UK, condylomata acuminata is the most commonly diagnosed viral sexually transmitted disease. The highest incidence is among females 20-24 years of age. The results of 6 studies to examine the prevalence of human papillomavirus suggest a rate of 1-13%, with a positive association to the prevalence of cervical intraepithelial neoplasia in that population. It is estimated that genital human papillomavirus infection has a 10% prevalence among men and women in the US 15-49 years of age: 1% have condylomata, 2% have lesions visible only by magnification with the colposcope or hand lens, and 7% have clinically inapparent infections. Human papillomavirus types 6 and 11 tend to cause condylomata and low-grade epithelial cell atypia, while types 16, 18, and 31 have been found in higher-grade intraepithelial neoplasia and invasive cervical cancers. Current evidence suggests a long latency between acquisition of genital papillomavirus infection and the development of cervical malignancy, with cervical cancer generally not developing until the 5th decade and beyond. From an epidemiologic point of view, the current research literature lacks evidence of careful selection and definition of study populations, consistent quality control of clinical and laboratory methods, and thorough statistical analyses. To make it more possible to compare the results of different studies, more attention to epidemiologic factors is needed.
CTLA-4: a negative regulator of autoimmune disease. (1996)

CTLA-4, a CD28 homologue expressed on activated T cells, binds with high affinity to the CD28 ligands, B7-1 (CD80) and B7-2 (CD86). This study was designed to examine the role of CTLA-4 in regulating autoimmune disease. Murine relapsing-remitting experimental autoimmune encephalomyelitis (R-EAE) is a demyelinating disease mediated by PLP139-151-specific CD4+ T cells in SJL/J mice. Anti-CTLA-4 mAbs (or their F(ab) fragments) enhanced in vitro proliferation and pro-inflammatory cytokine production by PLP139-151-primed lymph node cells. Addition of either reagent to in vitro activation cultures potentiated the ability of T cells to adoptively transfer disease to naive recipients. In vivo administration of anti-CTLA-4 mAb to recipients of PLP139-151-specific T cells resulted in accelerated and exacerbated disease. Finally, anti-CTLA-4 treatment of mice during disease remission resulted in the exacerbation of relapses. Collectively, these results suggest that CTLA-4 mediates the downregulation of ongoing immune responses and plays a major role in regulating autoimmunity.
Fecal DNA versus Fecal Occult Blood for Colorectal-Cancer Screening in an Average-Risk Population (2004)

Although the majority of neoplastic lesions identified by colonoscopy were not detected by either noninvasive test, the multitarget analysis of fecal DNA detected a greater proportion of important colorectal neoplasia than did Hemoccult II without compromising specificity.
Nanopore Tomography of a Laser Focus (2005)

We demonstrate that the ionic current through a solid-state nanopore can be used to measure at single nanometer resolution the three-dimensional intensity profile of a laser directly in the focus of a microscope objective. We find a linear dependence of the ionic current on the incident laser power since the laser-induced heat increases the temperature locally in the solution. Our data show a temperature increase of up to 20 K in the center of the focus for a laser wavelength of 1064 nm. Measurements of the two-dimensional temperature profiles at different positions along the optical axis allow us to reconstruct the three-dimensional temperature profile of the laser focus, similar to tomography. Our new technique does not rely on the help of any optical elements and allows quantitative measurement of optical intensity or temperature distributions in aqueous environments with nanometer resolution.
Phase 2 trial of the histone deacetylase inhibitor romidepsin for the treatment of refractory multiple myeloma (2010)

The results of the current study demonstrate that romidepsin, as a single agent, is unlikely to be associated with a response rate of ≥30% in patients with refractory myeloma, although there was some clinical evidence suggesting a biological effect associated with therapy.
Where is the energy spent inside my app? (2012)

Where is the energy spent inside my app? Despite the immense popularity of smartphones and the fact that energy is the most crucial aspect in smartphone programming, the answer to the above question remains elusive. This paper first presents eprof, the first fine-grained energy profiler for smartphone apps. Compared to profiling the runtime of applications running on conventional computers, profiling energy consumption of applications running on smartphones faces a unique challenge, asynchronous power behavior, where the effect on a component's power state due to a program entity lasts beyond the end of that program entity. We present the design, implementation and evaluation of eprof on two mobile OSes, Android and Windows Mobile.
Posttranscriptional effector domains in the Rev proteins of feline immunodeficiency virus and equine infectious anemia virus (1994)

By systematically dissecting the Rev proteins of feline immunodeficiency virus (FIV) and equine infectious anemia virus (EIAV), we have identified within each a short peptide that is functionally interchangeable with the effector domains found in Rev-like proteins from other retroviruses. The active sequences from FIV and EIAV differ in several respects from other known effectors and may represent a distinct class of effector domain.
Mammary carcinoma suppression by cellular retinoic acid binding protein-II. (2003)

Retinoic acid (RA) modulates cell proliferation, differentiation, and apoptosis, and is used in chemotherapy and chemoprevention in several human cancers. RA exerts its pleiotropic activities by activating the nuclear receptors, retinoic acid receptor (RAR), which, in turn, regulate transcription of multiple target genes. In cells, RA also associates with cellular RA-binding proteins [cellular RA binding proteins (CRABPs)-I and -II]. Recent studies revealed that CRABP-II functions by "channeling" RA to RAR, thereby enhancing the transcriptional activity of the receptor. In search for a biologically meaningful role for CRABP-II, we examined its effect on RA-induced growth inhibition in RA-resistant tumors. Stable expression of CRABP-II in mammary carcinoma SC115 cells enabled activation of RAR, considerably sensitized the cells to RA-induced growth inhibition, and dramatically suppressed their tumorigenicity in immunodeficient mice. Similarly, injection of an adenovirus expressing CRABP-II into mammary carcinomas that spontaneously develop in TgN(MMTVneu)202Mul mice resulted in a significant delay in tumor growth and in prolonged survival rates. Remarkably, in both mouse models, administration of exogenous RA had no additional beneficial effect, indicating that endogenous levels of RA are sufficient for maximal tumor suppression on CRABP-II overexpression. The observations reveal that CRABP-II plays a critical role in sensitizing tumors to the growth-suppressive activities of RA in vivo.
In vitro proliferation and differentiation of human CD34+ cells from peripheral blood into mature red blood cells with two different cell culture systems (2008)

Both LCs were able to generate fully matured RBCs and represent powerful tools for fundamental research in erythroid development and diseases targeting the erythroid lineage. A slightly higher proliferation was achieved in the 3P-LC. This was associated with a limited homogeneity due to more nonerythroid cells, however. Therefore the 2P-LC is favored, also saving additional culture days and growth factors.
Enzymatic Oxidation of Nicotine to Nicotine Δ1′(5′) Iminium Ion (1973)

Abstract Oxidation of nicotine in the presence of rabbit liver 10,000 x g supernatant, NADPH, and cyanide results in the production of 5'-cyanonicotine. NaBD4 reduction of the reaction mixture from a similar incubation of nicotine, NADPH, and supernatant results in the production of deuteronicotine having a single deuterium in the pyrrolidine ring. Oxidation of nicotine to cotinine under 18O2 did not lead to incorporation of 18O in the cotinine produced. These results are explained by the formation of nicotine Δ1'(5') iminium ion as an intermediate in the degradation of nicotine. The formation of the iminium ion is catalyzed by an enzyme system having the properties of a mixed function oxidase. The reaction requires NADPH and O2 and is inhibited by carbon monoxide. It is proposed the nicotine Δ1'(5') iminium ion is formed by loss of water from 5'-hydroxy nicotine. The iminium ion formed from nicotine represents a nicotine analogue with a markedly altered chemical reactivity and must therefore be considered in studies on the physiological action of nicotine.
ADP, thrombin, and Bothrops atrox thrombinlike enzyme in platelet-dependent fibrin retraction (1975)

Clots formed upon the addition of thrombin to human platelet-rich plasma (PRP) retracted readily but the clotting enzyme from Bothrops atrox venom did not cause retraction in PRP unless ADP, collagen, epinephrine, or low concentrations of thrombin (0.1 U) were added. The latter type of retraction was inhibited by apyrase and creatine phosphate kinase in the presence of creatine phosphate, but that induced with higher concentration of thrombin (2 U) was not. In a system composed of washed human platelets and purified fibrinogen, Bothrops marajoensis (BM) thrombinlike enzyme (highly purified preparations of viper venom) did not cause clot retraction. Addition of ADP to the platelet-fibrinogen mixture prior to BM enzyme resulted in stimulation of clot retraction that could be dissociated from the release of platelet constituents. Addition of low concentrations of thrombin (0.1 U/ml) caused retraction associated with a considerable release of adenine nucleotides that was inhibited by potato apyrase. Electron micrographs showed platelet-fibrin aggregates in all types of retracted clots. Nonretracted clots formed in the presence of potato apyrase contained discoidal platelets that were not in close association with fibrin. It has been postulated that platelet-dependent fibrin clot retraction induced by collagen, epinephrine, and low concentration of thrombin is mediated by ADP. High concentrations of thormbin may possibly promote clot retraction independently of ADP.
Nuclei of stroma: Site of highest estrogen concentration in human benign prostatic hyperplasia (1982)

In an earlier publication we found significantly more estrogen receptor-positive cases in the stroma if compared with the epithelium of human benign prostatic hyperplasia (BPH). We were therefore interested to find out whether this preferential assay of estrogen receptor in stroma is reflected by a higher estrogen content in this tissue fraction. Estradiol (E2) and estrone (E1) were measured by RIA in whole BPH tissue, stroma, and epithelium as well as in the nuclear fraction of stroma and epithelium. For comparison, E2 and E1 were measured in blood also. The main results are as follows: 1) In all BPH samples the E2 (26.0 +/- 3.5 (SEM) pg/g (n = 20)) and E1 (53.5 +/- 7.4 (14)) content was significantly higher than in the corresponding plasma (E2: 17.5 +/- 2.3 pg/ml (11); E1: 26.5 +/- 4.4(7)), the mean ratio of E2/E1 was 0.52 and 0.69 for BPH and plasma, respectively; 2) in stroma significantly more E2 (53.6 +/- 7.8 fmol/mg DNA (18)) and E1 (55.9 +/- 8.4 (12)) were measured than in epithelium (E2: 15.7 +/- 1.9 (16); E1: 20.7 +/- 3.2 (13)); 3) in nuclei of stroma significantly higher E2 (38.0 +/- 5.3 fmol/mg DNA (20)) and E1 (19.2 +/- 4.8 (14)) concentrations were present than in epithelium (E2: 6.8 +/- 3.1 (19); E1: 2.5 +/- 0.5 (13)), the mean ratio of E2/E1 for the nuclear fractions of stroma (2.3) and epithelium (2.7) increased dramatically if compared with the respective ratio in whole BPH tissue. In conclusion, there is a distinct accumulation of estrogens in the nuclei of stroma, E2 concentration being significantly higher than E1. These data support the hypothesis that E2 could play a preferential role in stimulating the growth of the BPH stroma.