gebhart/patrepeval huggingface dataset:
Cloning, sequencing and heterologous expression of the medermycin biosynthetic gene cluster of Streptomyces sp. AM-7161: towards comparative analysis of the benzoisochromanequinone gene clusters (2003)

Medermycin is a Streptomyces aromatic C-glycoside antibiotic classified in the benzoisochromanequinones (BIQs), which presents several interesting biosynthetic problems concerning polyketide synthase (PKS), post-PKS tailoring and deoxysugar pathways. The biosynthetic gene cluster for medermycin (the med cluster) was cloned from Streptomyces sp. AM-7161. Completeness of the clone was proved by the heterologous expression of a cosmid carrying the entire med cluster in Streptomyces coelicolor CH999 to produce medermycin. The DNA sequence of the cosmid (36 202 bp) revealed 34 complete ORFs, with an incomplete ORF at either end. Functional assignment of the deduced products was made for PKS and biosynthetically related enzymes, tailoring steps including strereochemical control, oxidation, angolosamine pathway, C-glycosylation, and regulation. The med cluster was estimated to be about 30 kb long, covering 29 ORFs. An unusual characteristic of the cluster is the disconnected organization of the minimal PKS genes: med-ORF23 encoding the acyl carrier protein is 20 kb apart from med-ORF1 and med-ORF2 for the two ketosynthase components. Secondly, the six genes (med-ORF14, 15, 16, 17, 18 and 20) for the biosynthesis of the deoxysugar, angolosamine, are all contiguous. Finally, the finding of a glycosyltransferase gene, med-ORF8, suggests a possible involvement of conventional C-glycosylation in medermycin biosynthesis. Comparison among the three complete BIQ gene clusters - med and those for actinorhodin (act) and granaticin (gra) - revealed some common genes whose deduced functions are unavailable from database searches (the 'unknowns'). An example is med-ORF5, a homologue of actVI-ORF3 and gra-ORF18, which was highlighted by a recent proteomic analysis of S. coelicolor A3(2).
Helix-destabilizing properties of the adenovirus DNA-binding protein (1994)

The adenovirus DNA-binding protein (DBP) is a multifunctional protein that is essential for viral DNA replication. DBP binds both single-stranded and double-stranded DNA as well as RNA in a sequence-independent manner. Previous studies showed that DBP does not promote melting of duplex poly(dA-dT) in contrast to prokaryotic single-strand-binding proteins. However, here we show that DBP can displace oligonucleotides annealed to single-stranded M13 DNA. Depending upon the DBP concentration, strands of at least 200 nucleotides can be unwound. Although unwinding of short (17-bp), fully duplex DNA is facilitated by DBP, unwinding of larger (28-bp) duplexes is only possible if single-stranded protruding ends are present. These protruding ends must be at least 4 nucleotides long for optimal unwinding, and both 5' and 3' single-stranded overhangs suffice. DBP-promoted strand displacement is sensitive to MgCl2 and NaCl and not dependent upon ATP. Our results suggest that DBP, through formation of a protein chain on the displaced strand, may destabilize duplex DNA ahead of the replication fork, thereby assisting in strand displacement during replication.
Analysis of fractal-shaped antennas using the multiperiodic traveling wave Vee model (2002)

A novel analytical model to predict the radiation performance of the Sierpinski fractal multiband antenna is presented. The theoretical development allows one to accurately predict the antenna response to flare angle variations and also to calculate the radiation patterns of other fractal-shaped antennas.
From fibroblasts to iPS cells: Induced pluripotency by defined factors (2008)

Patient-specific pluripotent cells may serve as a limitless source of transplantable tissue to treat a number of human blood and degenerative diseases without causing immune rejection. Recently, isolation of patient-specific induced pluripotent stem (iPS) cells was achieved by transducing fibroblasts with four transcription factors, Oct4, Sox2, Klf4, and c-Myc. However, the use of oncogenes and retrovirus in the current iPS cell establishment protocol raises safety concerns. To generate clinical quality iPS cells, the development of novel reprogramming methods that avoid permanent genetic modification is highly desired. The molecular mechanisms that mediate reprogramming are essentially unknown. We argue that establishment of a stable and self-sustainable ES-specific transcriptional regulatory network is essential for reprogramming. Such a system should include expression of Oct4, Sox2, Nanog and probably other pluripotenty-promoting factors from endogenous loci and establishment of a permissive epigenetic state to maintain such expression. In addition, though not yet proven experimentally, overcoming cellular senescence of fibroblasts by inactivating Rb and p53 pathways and up-regulating telomerase activity may also be required.
Detection of multi-tone signals based on energy operators (2002)

A nonlinear approach based on the Teager-Kaiser energy operator for multi-tone detection in the presence of voice is presented. The approach is shown to provide accurate frequency estimation, robustness against network distortions, good rejection of tone-like speech, with a significantly lower computational load when compared to classical tone detection approaches.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
All-digital phase-domain TX frequency synthesizer for Bluetooth radios in 0.13μm CMOS (2004)

An all-digital frequency synthesizer for a single-chip Bluetooth radio is fabricated in 0.13/spl mu/m CMOS, and operates in a digitally-synchronous phase domain that naturally incorporates wideband GFSK modulation. The synthesizer includes a pulse-shaping TX filter and near class-E PA with digital amplitude control. Close-in phase noise is -86.2dBc/Hz, integrated rms phase noise is 0.9/spl deg/, and settling time is /spl les/ 50/spl mu/s.
Test de Raven, baremos argentinos para el rango 19-30 años y efecto Flynn (2020)

This article aims to show the final results of the research project devoted to build norms for Raven’s Standard Progressive Matrices (Raven, Raven, &amp; Court, 2003), on subjects aged 19 to 30 years old in the city of La Plata, Argentina. The sample consisted of 979 subjects of both sexes, and was divided into four age groups. The results show that as the participant’s age increases, the average group’s performance improves, and variability remains similar between groups. There were no statistically significant differences found between sexes, or between the current results and those from the 2000 norms. It was found that the scores’ increase, expected according to the Flynn effect, has stopped, and the possible intergenerational cognitive differences which could explain this phenomenon are discussed. These results are also compared with those from recent research made in other countries.
Index guiding dependent effects in implant and oxide confined vertical-cavity lasers (1996)

Implant and oxide confined vertical-cavity surface-emitting lasers are compared in terms of properties dependent upon the nature of index guiding in the two structures including CW threshold current scaling with size, light-current linearity, pulsed operation delay, and beam profiles. The oxide confined lasers, fabricated by wet thermal oxidation, have a built-in index guide and thus exhibit substantially better properties than do lasers from the same wafer fabricated by proton implantation which rely on a thermal lens to reduce diffraction losses.
A single engineered amino acid substitution changes antibody fine specificity. (1994)

During the acquisition of humoral immunity, the process of somatic hypermutation introduces nucleotide substitutions into expressed antibody (Ab) V region genes. Studies employing in vitro mutagenesis have shown that recurrent mutations observed in vivo often enhance the affinity of the target Ab for Ag. Here we show that a single amino acid replacement at position 35 in the H chain of an unmutated Ab with specificity for p-azophenylarsonate (Ars) confers specificity for the structurally related hapten p-azophenylsulfonate (Sulf) while abolishing specificity for Ars. The mutant Ab binds Sulf with an affinity characteristic of Ab produced by memory B cells. The same mutation in the somatically mutated anti-Ars Ab 36-71, for which the Fab crystal structure is known, resulted in a significant shift in fine specificity from Ars to Sulf. Examination of the crystal structure suggests that the specificity change is caused by a decrease in binding site size and/or new hydrogen bond geometry. Because the mutation at position 35 had been observed in somatically mutated Ab elicited by immunization with Ars followed by Sulf, the results confirm that somatic mutation in vivo can alter Ab specificity. The results also support the potential of Ab engineering to alter antigenic specificity.
7.6 A 90nm embedded 1T-MONOS flash macro for automotive applications with 0.07mJ/8kB rewrite energy and endurance over 100M cycles under Tj of 175°C (2016)

The computerization of automotive control has expanded the application range of micro controller units (MCUs). A high-end engine-control unit (ECU) requires high-performance Flash MCUs, which integrate high-speed CMOS logic and large high-performance embedded Flash memories (eFlash) [1,2]. There are also broad markets for motor control MCUs: used to control actuators in parts such as seats, windows, and mirrors. In order to integrate analog circuits to control the high voltage (HV) drivers in these parts, those MCUs have been manufactured in Flashless process, and external EEPROM chips are being used. EEPROM chips work as “learning memories” which store the calibration data to optimize analog circuit performance in the field. Replacement of external EEPROM chips by eFlash, resulting in less additional process cost and higher rewrite endurance, is a requirement for more elaborate learning at a higher data sampling rate. In addition to automotive grade reliability under extremely harsh temperature conditions, low power consumption is also a strong requirement as the number of MCUs used in motor control systems is increasing.
Hyperimmune globulins in prevention and treatment of respiratory syncytial virus infections (1995)

Respiratory syncytial virus (RSV) is an important community and nosocomial respiratory pathogen for infants and young children. RSV causes especially severe disease in the prematurely born or those with chronic cardiopulmonary diseases. Elderly persons and those with T-cell deficiencies, such as bone marrow transplant recipients, are also at high risk for serious lower respiratory tract infections. To date, prevention of RSV infections by vaccination has proven elusive and no preventive drugs exist. Studies in animals and humans have shown that the lower respiratory tract can be protected from RSV infection by sufficient circulating RSV neutralizing antibody levels. Recently, an RSV hyperimmune immune globulin (RSVIG) was developed and tested for the prevention of RSV infections or reduction of disease severity. Passive immunization of high-risk children with RSVIG during the respiratory disease season effected significant reductions in RSV infections, hospitalizations, days of hospitalization, intensive care unit admissions, days in the intensive care unit, and ribavirin use. Studies in cotton rats and owl monkeys show that RSV infections can also be treated with inhalation of immune globulin at doses substantially smaller than required for parenteral treatment. Therapeutic trials of parenteral RSVIG have been completed and are pending analysis. The use of polyclonal, hyperimmune globulins and perhaps human monoclonal antibodies provides an additional approach to the prevention and perhaps the treatment of certain viral lower respiratory tract infections such as those caused by RSV.
Comparison by 1H‐nmr spectroscopy of the conformation of the 2600 dalton antifreeze glycopeptide of polar cod with that of the high molecular weight antifreeze glycoprotein (1987)

Abstract The antifreeze glycopeptide (AFGP‐8) from polar cod, B. saida , is a 14‐amino acid polypeptide having alternating glycotripeptide sequences of Ala‐[Gal(β1 → 3)GalNAc(β1 → O)]‐Thr‐Pro and Ala‐[Gal(β1 → 3)GalNAc(β1 → O)]‐Thr‐Ala, with alanyl residues at amino and carboxy terminals. Conformational studies of AFGP‐8 have been carried out by 1 H‐nmr and empirical energy calculations to investigate the difference in its antifreeze behavior from that of the more active high‐molecular weight AFGP 1‐4 of P. borchgrevinki . The 1 H‐nmr spectra, including the resonances of the exchangeable amide protons, were assigned by two‐dimensional correlated spectroscopy (COSY), one‐dimensional difference decoupling, and nuclear Overhauser effect (NOE) measurements. For the four threonyl residues, the amide proton coupling constants and the small coupling constants between H α and H β indicate similar conformations, despite significant chemical shift differences. The strong NOE between the α protons and the amide protons of the residue following together with large temperature coefficients of chemical shifts, indicate an extended conformation not consisting of α‐helix, turns or bends. Energy computations indicate several low‐energy conformations consistent with the observed coupling constants for ϕ. Among these, a left‐handed helical conformation with three repeating residues per turn has been proposed, which is in accordance with the observed NOE between the methyl group of the α‐GalNAc and Ala H β s. While the observed Overhauser effects in the threonyl side chain suggest a certain amount of conformational averaging, the effect involving the acetmido methyl of α‐GalNAc and H β s of Ala indicate that it as is a major conformer. In view of the close similarity between the conformations of AFGP‐8 and the more active antifreeze polymer, AFGP 1‐4, we propose that the difference in their activities is due to the length of the regular repeating structure with glycosylation at every third amino acid residue, and not due to any fundamental difference in their conformations.
A simple, rapid, low-cost diagnostic test for sickle cell disease (2013)

This communication describes a very simple, rapid and inexpensive point-of-care diagnostic test for sickle cell disease (SCD) that can conclusively differentiate between blood samples from normal healthy individuals, sickle cell trait carriers and SCD patients using the characteristic blood stain patterns produced by each sample on paper.
Highly Selective Phosphodiesterase 4 Inhibitors for the Treatment of Allergic Skin Diseases and Psoriasis (2007)

The phosphodiesterase (PDE) 4 is the predominant cyclic AMP degrading enzyme in a variety of inflammatory cells including eosinophils, neutrophils, macrophages, T cells and monocytes. In addition, this enzyme is expressed in non-immune cells such as keratinocytes and fibroblasts. Highly selective PDE4 inhibitors are currently under evaluation for the treatment of asthma and/or chronic obstructive pulmonary disease. Due to the broad anti-inflammatory/immuno-modulatory action of PDE4 inhibitors, it has been proposed that PDE4 inhibitors might also be efficacious for skin disorders such as atopic dermatitis. Consequently, PDE4 inhibitors including cilomilast and AWD 12-281 have been tested in several models of allergic and irritant skin inflammation. These PDE4 inhibitors displayed strong anti-inflammatory action in models of allergic contact dermatitis in mice, in the arachidonic acid induced skin inflammation in mice and in ovalbumin sensitised guinea pigs. The determination of cytokines in skin homogenates revealed that both Th1 as well as Th2 cytokines are suppressed by PDE4 inhibitors, indicating an anti-inflammatory activity in both the Th2 dominated acute phase as well as the Th1 dominated chronic phase of atopic dermatitis. Due to the suppression of Th1 cytokines, activity can also be expected in psoriasis. Results of early clinical trials with both topically (cipamfylline, CP80,633) and systemically (CC-10004) active PDE4 inhibitors demonstrated efficacy in atopic dermatitis and in the case of CC-10004, also in psoriasis. AWD 12-281 (GW 842470) is currently under clinical evaluation for the topical treatment of atopic dermatitis. Results concerning clinical efficacy of this potent and selective PDE4 inhibitor are anxiously awaited.
Strategies for Managing Transient Rates (1990)

Yield-oriented transient-rate management can help hotel owners achieve their profit objectives. Here's how you can make it work for you
Effect of interleukin-1 on lipid metabolism in the rat. Similarities to and differences from tumor necrosis factor. (1991)

Infection and inflammation are associated with hypertriglyceridemia, which is thought to be mediated by cytokines. Previous studies at our laboratory and others have shown that tumor necrosis factor acutely increases serum triglyceride levels primarily by stimulating hepatic lipid synthesis and secretion. The role of interleukin-1 (IL-1), a cytokine that is also secreted by stimulated macrophages and that has many actions that overlap those of tumor necrosis factor, has not been studied in depth. The present study demonstrates that IL-1, at doses similar to those that cause fever and anorexia and that stimulate adrenocorticotropic hormone secretion, rapidly increases serum triglyceride levels; this elevation persists for at least 17 hours. Serum cholesterol levels are not altered by IL-1. Neither is the clearance of triglyceride-rich lipoproteins affected by IL-1. However, hepatic triglyceride secretion, measured by the Triton WR-1339 technique, is increased in IL-1-treated animals. Accompanying this stimulation in hepatic lipid secretion is an increase in de novo fatty acid synthesis in the liver. IL-1 does not increase serum free fatty acid and glycerol levels, suggesting that IL-1 does not stimulate lipolysis in vivo. Additionally, inhibition of lipolysis does not prevent the increase in serum triglyceride levels, providing further evidence that lipolysis does not play a crucial role in the increased hepatic lipid synthesis and secretion induced by IL-1. In contrast, tumor necrosis factor increases lipolysis, which contributes to the increase in serum triglycerides. That multiple cytokines rapidly elevate plasma triglyceride levels suggest that these changes in lipid metabolism may play an important role in the organism's response to infection and inflammation.
Valine dehydrogenase from Streptomyces albus: gene cloning, heterologous expression and identification of active site by site-directed mutagenesis (2000)

A gene encoding valine dehydrogenase (Vdh) has been cloned from Streptomyces albus, a salinomycin producer, and expressed in Escherichia coli. The S. albus Vdh is composed of 364 amino acids that showed high homology with several other amino acid dehydrogenases as well as Vdhs from Streptomyces spp. and leucine and phenylalanine dehydrogenases (Ldh and Pdh) from Bacillus spp. A protein of 38 kDa, corresponding to the approximate mass of the predicted S. albus Vdh product (38.4 kDa) exhibiting specific Vdh activity, was observed when the S. albus vdh gene was overexpressed in E. coli under the controlled T7 promoter and was subsequently purified to homogeneity. Among branched- and straight-chain amino acids, L-valine and L-α-aminobutyrate were the preferred substrates for the enzyme. Lys-79 and Lys-91 of S. albus Vdh were highly conserved in the corresponding region of NAD(P)+-dependent amino acid dehydrogenase sequences. To elucidate the functional roles of the lysyl residues, the Lys residues have individually been replaced with Ala by site-directed mutagenesis. Kinetic analyses of the Lys-79 and Lys-91-mutated enzymes revealed that they are involved in the substrate binding site and catalysis, respectively, analogous to the corresponding residues in the homologous Ldh and Pdh.
Quantification of Sulforaphane Mercapturic Acid Pathway Conjugates in Human Urine by High-Performance Liquid Chromatography and Isotope-Dilution Tandem Mass Spectrometry (2008)

We report validation of the first high-pressure liquid chromatography isotope-dilution mass spectrometry method to measure sulforaphane (SFN) and its glutathione-derived conjugates in human urine. As epidemiological evidence continues to mount that the consumption of a diet rich in cruciferous vegetables may reduce the risk of certain cancers, the development of analytical methodologies to accurately measure isothiocyanates (ITCs) and their subsequent metabolic products becomes paramount. SFN, the principal ITC produced by broccoli, is an effective chemopreventive agent with multiple modes of action. SFN and SFN conjugates have often been measured collectively utilizing a cyclocondensation assay with 1,2-benzenedithiol. More recently, some of the major SFN conjugates have been determined using mass spectrometry. Here, triple-quadrupole mass spectrometry has been coupled with the use of stable isotope-labeled internal standards of D8-SFN and all four D8-SFN mercapturic acid pathway conjugates to provide an accurate, precise, sensitive, and specific method for analysis of these compounds. Using urine samples collected during an earlier intervention with broccoli sprouts, the concentrations of SFN, SFN-cysteine, and the mercapturic acid SFN- N-acetylcysteine were sufficiently high such that as little as 50 nL of urine was required for analysis. Although each study participant received an equivalent dose of broccoli sprout preparation, the interindividual conversion of the precursor glucosinolate to SFN varied over 100-fold. These 98 urines provided an ideal sample set for examining the robustness of the assay. The mean urinary concentrations +/- standard deviations in overnight voids following ingestion of the first dose were 4.7 +/- 5.1, 0.03 +/- 0.05, 0.06 +/- 0.06, 18 +/- 15, and 42 +/- 23 nmol/mg creatinine for SFN, SFN-glutathione, SFN-cysteine-glycine, SFN-cysteine, and SFN- N-acetylcysteine, respectively. This method determines SFN and all four SFN glutathione-derived metabolites with minimal sample preparation and will be extremely useful in understanding the role of SFN-rich foods in preventing cancer and other chronic diseases.
Regulation of melanogenesis in B16 mouse melanoma cells by protein kinase C (1996)

Melanogenesis is regulated by a variety of environmental and hormonal factors. In this study, we showed that protein kinase C (PKC) plays a major role in regulating melanogenesis in B16 mouse melanoma cells. Chronic treatment of B16 cells with phorbol dibutyrate resulted in a concentration-dependent loss of density-dependent induction of tyrosinase activity, which correlated positively with a concentration-dependent loss of PKC enzyme activity. In contrast, B16 clones overexpressing PKC alpha had increased tyrosinase activity. Different phorbol derivatives inhibited tyrosinase activity and depleted cellular PKC alpha in a manner that reflected their reported tumor-promoting activity. Western blotting analysis showed that phorbol dibutyrate decreased the amount of the brown locus gene product (TRP-1) by 50% and lowered the amount of the albino locus gene product (tyrosinase) to undetectable levels. None of the phorbol derivatives affected the level of the slaty locus protein (TRP-2). The decrease in tyrosinase and TRP-1 protein levels was found to be due to a decrease in the mRNA encoded by these genes. In addition to inhibiting the density-dependent increase in tyrosinase activity, phorbol dibutyrate inhibited some, but not all, of the 8-bromocyclic AMP-induced increase in tyrosinase activity. This was accompanied by a decrease in the amount of tyrosinase protein induced by 8-bromocyclic AMP. Although 8-bromocyclic AMP did not change the level of TRP-1, it did reverse the decrease in the amount of this protein induced by phorbol dibutyrate. The amount of TRP-2 was not altered by any of these agents. These data suggest that PKC regulates melanogenesis primarily by controlling the constitutive expression of tyrosinase and, to a lesser extent, TRP-1.