gebhart/patrepeval huggingface dataset:
Masters change, slaves remain (2002)

Sex determination offers an opportunity to address many classic questions of developmental biology. In addition, because sex determination evolves rapidly, it offers an opportunity to investigate the evolution of genetic hierarchies. Sex determination in Drosophila melanogaster is controlled by the master regulatory gene, Sex lethal (Sxl). DmSxl controls the alternative splicing of a downstream gene, transformer (tra), which acts with tra2 to control alternative splicing of doublesex (dsx). DmSxl also controls its own splicing, creating an autoregulatory feedback loop that ensures expression of Sxl in females, but not males. A recent paper has shown that in the dipteran Ceratitis capitata later (downstream) steps in the regulatory hierarchy are conserved, while earlier (upstream) steps are not. Cctra is regulated by alternative splicing and apparently controls the alternative splicing of Ccdsx. However, Cctra is not regulated by CcSxl. Instead it appears to autoregulate in a manner similar to the autoregulation seen with DmSxl.
General pharmacology of ramipril. (1988)

General pharmacological properties of (+)-(1S,3S,5S)-2-[(S)-N-[(S)-1-ethoxycarbonyl-3-phenyl-propyl] alanyl]-2-azabicyclo[3.3.0]octane-3-carboxylic acid (ramipril, Hoe 498), a new prodrug non-sulfhydryl angiotensin converting enzyme inhibitor and its active diacid metabolite, ramiprilat, were examined. Both ramipril and ramiprilat were without effect on basal central and autonomic nervous systems in rats and mice. Ramipril given intravenously to anaesthetized normotensive dogs produced a slight fall in blood pressure but did not significantly alter other cardio-hemodynamic functions. Also, ramiprilat was without effect on isolated atria and airway resistance of guinea pigs. Oral administration of ramipril to dogs increased renal blood flow but did not significantly affect other renal parameters, for example, glomerular filtration rate and electrolyte excretion. Ramipril produced a competitive inhibition of late proximal tubular secretion which points to in part renal secretory excretion of ramipril and/or its metabolites. Compared to urea-induced diuresis in rats, ramipril was without direct diuretic activity. Ramipril exerted little, if any, influence on gastric bile and pancreatic secretion or intestinal transit in rats, as well as on concentration of glucose and lipoproteins, blood coagulation, platelet aggregation and vascular permeability in rats, rabbits or dogs. The carrageenin-induced rat paw edema was enlarged by ramipril, but there was no such effect on serotonin-, dextran- or ovalbumin-induced edemas which in contrast to carrageenin do not involve bradykinin. Thus, undesired cutaneous reactions might result from locally released bradykinin.(ABSTRACT TRUNCATED AT 250 WORDS)
Defect structure and electron field-emission properties of boron-doped diamond films (1999)

The correlation between electron field-emission properties of diamond films prepared by the chemical vapor deposition (CVD) process and the defect structure induced by boron doping was examined. Secondary ion mass spectroscopic analysis indicates that the solubility limit of boron in diamond is (B3+)2=5×1021 cm−3, whereas the infrared absorption (IR) spectroscopic analysis reveals that the largest boron concentration that can be incorporated as substitutional dopants is only one tenth of the solubility limit, (B3+)d=5×1020 cm−3. Including boron species higher than this concentration induces large strain and atomic defects, which are inferred by the distorted Raman resonance peak, noisy IR spectra, and twinned microstructure for diamond. Presumably, the presence of atomic defects, which behave as electron traps, is the mechanism deteriorating the electron field-emission properties of CVD diamonds.
The multipole resonance probe: Realization of an optimized radio-frequency plasma probe based on active plasma resonance spectroscopy (2010)

A diagnostic concept is presented which enables the simultaneous determination of plasma density, electron temperature, and collision rate in low-pressure gas discharges. The proposed method utilizes a radio-frequency driven probe of particular spherical design which is immersed in the plasma to excite a family of spatially bounded surface resonances. An analysis of the measured absorption spectrum S(ω) of the probe provides information on the distribution of the plasma in its vicinity, from which the values of the plasma parameters can be inferred. In its simplest realization, the probe consists of two dielectrically shielded, conducting hemispheres, which are symmetrically driven by a radio-frequency source, and the excited resonances can be classified as multipole fields, which allows an analytical evaluation of the measured signal. A comparison of the analytical results, 3D-field simulations, and first measurements of a prototype show the functionality of the presented probe concept.
Hochdynamische Strom- und Spannungsregelung von permanenterregten Synchronmaschinen auf Basis von Delta-Sigma Bitströmen (2016)

Delta-Sigma-Umsetzer sind aus der Audio-Technik für ihren hohen Signal-zu-Rausch Abstand bei Abtastraten im 10 bis 100 kHz Bereich bekannt und werden zunehmend auch in der Stromregelung von elektrischen Antrieben als Analog-Digital-Umsetzer eingesetzt. Delta-Sigma-Umsetzer bestehen aus einem Modulator und einem digitalen Tiefpassfilter. Die Auswirkungen des digitalen Filters auf die Stromregelung eines elektrischen Antriebs werden hinsichtlich der erreichbaren Bandbreite des Stromregelkreises und der Unterdrückung von Störungen in der Strommessung untersucht. In dieser Arbeit werden zwei Ansätze zur Steigerung der Bandbreite des Stromregelkreises verfolgt. Der Stromregler wird direkt in dem hochfrequenten Zeitraster (10 MHz) der Delta-Sigma-Modulatoren gerechnet, so dass auf einen digitalen Tiefpassfilter verzichtet werden kann. Dieses Vorgehen erfordert eine neuartige Signalverarbeitung, da der Ausgang des Delta-Sigma-Modulators aus einem gering quantisierten Delta-Sigma-Bitstrom mit einer Auflösung von einem Bit besteht. Die vorhandenen Ansätze zur direkten Signalverarbeitung des Delta-Sigma-Bitstroms werden verglichen und erweitert. Der zweite Ansatz zur Steigerung der Bandbreite besteht darin, die hochfrequenten Delta-Sigma-Bitströme breitbandig in PWM Signale für eine Leistungselektronik im 4 - 40 kHz Bereich umzusetzen. Das grundsätzliche Prinzip wird an einer einphasigen Last untersucht. Die im Stand der Forschung bekannte Lösung für eine dreiphasige Last weist erhebliche Nachteile auf. In dieser Arbeit wird ein Verfahren für einen hochdynamischen dreiphasigen Leistungselektronik-Modulator zur direkten Verarbeitung von Delta-Sigma-Bitströmen vorgestellt, welcher die Nachteile der bekannten Lösung aufhebt. Zusätzlich wird eine direkte Rückführung der Strom- und Spannungsmesswerte über Delta-Sigma-Bitströme realisiert. Dies ermöglicht eine hochdynamische Strom- und Spannungsregelung einer permanenterregten Synchronmaschine.
How does the presence of stevia glycosides impact surface bubbles stability? (2020)

The addition of sweeteners in fizzy beverages not only affects the sugar content but also the bubbles stability. In this article, we propose a model experiment, in which the lifetime of hundreds of single bubbles is measured, to assess the stability of bubbles in solutions containing either sucrose or sweeteners. We show that the bubbles are indeed more stable in presence of sweeteners, which are surface active molecules and adsorb at the interface. Additionally, we test an antifoam at different concentrations and show that our experiment allows to identify the best concentration to reproduce the stability obtained in sucrose when we replace this latter by a sweetener.
Reducing the height of a circular array of monopoles using top hats and dielectric coatings (2004)

Using a Radial Guide Field Matching Method, an investigation is performed into reducing the height of an electronically steered circular array of monopole antennas composed of a central active element surrounded by passive elements being either short‐ or open‐circuited. It is shown that a considerable height reduction can be achieved using top hats attached to monopoles ends and by applying dielectric coating underneath the top hats. The trade‐off in achieving height reduction is narrower impedance bandwidth.
Single-molecule denaturation and degradation of proteins by the AAA+ ClpXP protease (2009)

ClpXP is an ATP-fueled molecular machine that unfolds and degrades target proteins. ClpX, an AAA+ enzyme, recognizes specific proteins, and then uses cycles of ATP hydrolysis to denature any native structure and to translocate the unfolded polypeptide into ClpP for degradation. Here, we develop and apply single-molecule fluorescence assays to probe the kinetics of protein denaturation and degradation by ClpXP. These assays employ a single-chain variant of the ClpX hexamer, linked via a single biotin to a streptavidin-coated surface, and fusion substrates with an N-terminal fluorophore and a C-terminal GFP-titin-ssrA module. In the presence of adenosine 5'-[gamma-thio]triphosphate (ATPgammaS), ClpXP degrades the titin-ssrA portion of these substrates but stalls when it encounters GFP. Exchange into ATP then allows synchronous resumption of denaturation and degradation of GFP and any downstream domains. GFP unfolding can be monitored directly, because intrinsic fluorescence is quenched by denaturation. The time required for complete degradation coincides with loss of the substrate fluorophore from the protease complex. Fitting single-molecule data for a set of related substrates provides time constants for ClpX unfolding, translocation, and a terminal step that may involve product release. Comparison of these single-molecule results with kinetics measured in bulk solution indicates similar levels of microscopic and macroscopic ClpXP activity. These results support a stochastic engagement/unfolding mechanism that ultimately results in highly processive degradation and set the stage for more detailed single-molecule studies of machine function.
Peripheral modulation of pain in conscious guinea pigs: effect of morphine, nalorphine and clonidine. (1988)

1. Morphine and nalorphine were shown to have a peripheral analgesic effect on conscious guinea pigs, producing a decrease in the vocalization response to noxious electrical stimulation. Naloxone antagonized the effect of morphine and nalorphine. 2. Locally administered clonidine had a peripheral analgesic effect on conscious guinea pigs, producing a decrease in the vocalization response to noxious electrical stimulation. 3. The peripheral analgesia of clonidine was antagonized by yohimbine and naloxone. The analgesic effect of clonidine was 250-300 times more potent than that of lidocaine. 4. It is suggested that alpha 2-adrenergic receptor agonists may activate enkephalin-like substances released at the peripheral level.
Understanding the Autocatalytic Process of Pro‐kumamolisin Activation from Molecular Dynamics and Quantum Mechanical/Molecular Mechanical (QM/MM) Free‐Energy Simulations (2013)

Simulations: Molecular dynamics simulations showed that protonation of Asp164 triggers conformational changes and leads to reconstruction of the functional active site for the cleavage of the prodomain. Quantum mechanical/molecular mechanical (QM/MM) free-energy simulations revealed the catalytic mechanism and energetics for the acylation reaction of the autocatalytic process (see figure).
Salt Bridges Destabilize a Leucine Zipper Designed for Maximized Ion Pairing between Helices (2002)

Interhelical salt bridges are common in leucine zippers and are thought to stabilize the coiled coil conformation. Here we present a detailed thermodynamic investigation of the designed, disulfide-linked leucine zipper AB(SS) whose high-resolution NMR structure shows six interhelical ion pairs between heptad positions g of one helix and e' of the other helix but no ion pairing within single helices. The average pK(a) value of the Glu side chain carboxyl groups of AB(SS) is slightly higher than the pK(a) of a freely accessible Glu in an unfolded peptide [Marti, D. N., Jelesarov, I., and Bosshard, H. R. (2000) Biochemistry 39, 12804-12818]. This indicates that the salt bridges are destabilizing, a prediction we now have confirmed by determining the pH +/- stability profile of AB(SS). Circular dichroism-monitored unfolding by urea and by heating and differential scanning calorimetry show that the coiled coil conformation is approximately 5 kJ/mol more stable when salt bridges are broken by protonation of the carboxyl side chains. Using guanidinium chloride as the denaturant, the increase in the free energy of unfolding on protonation of the carboxyl side chains is larger, approximately 17 kJ/mol. The discrepancy between urea and guanidinium chloride unfolding can be ascribed to the ionic nature of guanidinium chloride, which screens charge-charge interactions. This work demonstrates the difficulty of predicting the energetic contribution of salt bridges from structural data alone even in a case where the ion pairs are seen in high-resolution NMR structures. The reason is that the contribution to stability results from a fine balance between energetically favorable Coulombic attractions and unfavorable desolvation of charges and conformational constraints of the residues involved in ion pairing. The apparent discrepancy between the results presented here and mutational studies indicating stabilization by salt bridges is discussed and resolved. An explanation is proposed for why interhelical salt bridges are frequently found in natural coiled coils despite evidence that they do not directly contribute to stability.
Risperidone in the treatment of conduct disorder in preschool children without intellectual disability (2011)

The results of this study suggest that risperidone may be an effective and well-tolerated atypical antipsychotic for the treatment of CD in otherwise normally developing preschool children. The findings of the study should be interpreted as preliminary data considering its small sample size and open-label methodology.
Electrically-Induced DNA Transfer into Cells. Electrotransfection in Vivo (1994)

Electrotransfection, or transfection by electroporation (Neumann et al., 1982), is becoming more and more popular as a powerful tool for introduction of exogenous DNA into cells of virtually any origin (Potter et al., 1984, Fromm et al., 1985, Dower et al., 1988, Potter, 1988). In many cases, electroporation is the only method that works. Ultimately, it is because electrotransfection is to a great extent a physical rather than biological technique. In contrast to the traditional method of mammalian cell transformation by calcium phosphate-DNA coprecipitate (Graham and Van der Eb, 1973), which is efficient predominantly with fibroblastlike cells, practically all types of mammalian and other cells attempted are successfully transfected by electroporation (Potter, 1988). This is one of the reasons why electrotransfection is regarded as promising for human gene therapy.
Synthesis, Physicochemical Properties, and Preliminary Biological Characterizations of a Novel Amphoteric Agmatine-Based Poly(amidoamine) with RGD-Like Repeating Units (2006)

A linear, amphoteric poly(amidoamine) nicknamed AGMA1, based on 4-aminobutylguanidine, or agmatine, was successfully prepared by Michael-type polyaddition of monoprotonated agmatine and 2,2-bis(acrylamido)acetic acid (BAC). Copolymers between AGMA1 and the biocompatible poly(amidoamine) ISA23 (deriving from the polyaddition of 2-methylpiperazine with BAC) were also prepared. Acid-base titrations gave for AGMA1 three acid dissociation constants, with pKa values of 2.25, 7.45, and >or=12.1, corresponding to a strong acid, a medium-weak base, and a strong base, respectively. The charge distribution profiles show that this polymer is prevailingly cationic at all physiological pH values, the positive net average charge per unit varying from about 0.5 at pH 7.4 to about 1.0 at pH 5, with an isoelectric point at pH approximately 10. Zeta-potential measurements confirmed this. Despite that, AGMA1 is nontoxic and nonhemolytic in vitro within all pH ranges tested (4-7.5). This is in contrast with the previously observed behavior of amphoteric PAAs, for instance ISA23, that are weakly hemolytic at pH 7.4 but highly hemolytic at pH 5/5.5. The lack of hemolytic activity of AGMA1 even at acidic pH values seems typical of the agmatine-BAC sequences and may be ascribed to their RGD-like structure. In fact, AGMA1-ISA23 copolymers behave in a way increasingly similar to that of ISA23; that is, they become hemolytic at low pH values as their ISA23 content increases.
CpxR/OmpR Interplay Regulates Curli Gene Expression in Response to Osmolarity in<i>Escherichia coli</i> (2005)

Curli fibers could be described as a virulence factor able to confer adherence properties to both abiotic and eukaryotic surfaces. The ability to adapt rapidly to changing environmental conditions through signal transduction pathways is crucial for the growth and pathogenicity of bacteria. OmpR was shown to activate csgD expression, resulting in curli production. The CpxR regulator was shown to negatively affect curli gene expression when binding to its recognition site that overlaps the csgD OmpR-binding site. This study was undertaken to clarify how the interplay between the two regulatory proteins, OmpR and CpxR, can affect the transcription of the curli gene in response to variation of the medium osmolarity. Band-shift assays with purified CpxR proteins indicate that CpxR binds to the csgD promoter region at multiple sites that are ideally positioned to explain the csg repression activity of CpxR. To understand the physiological meaning of this in vitro molecular phenomenon, we analyzed the effects of an osmolarity shift on the two-component pathway CpxA/CpxR. We establish here that the Cpx pathway is activated at both transcriptional and posttranscriptional levels in response to a high osmolarity medium and that CpxR represses csgD expression in high-salt-content medium, resulting in low curli production. However, csgD repression in response to high sucrose content is not mediated by CpxR but by the global regulatory protein H-NS. Therefore, multiple systems (EnvZ/OmpR, Cpx, Rcs, and H-NS) appear to be involved in sensing environmental osmolarity, leading to sophisticated regulation of the curli genes.
A Global-Model Naive Bayes Approach to the Hierarchical Prediction of Protein Functions (2009)

In this paper we propose a new global-model approach for hierarchical classification, where a single global classification model is built by considering all the classes in the hierarchy - rather than building a number of local classification models as it is more usual in hierarchical classification. The method is an extension of the flat classification algorithm naive Bayes. We present the extension made to the original algorithm as well as its evaluation on eight protein function hierarchical classification datasets. The achieved results are positive and show that the proposed global model is better than using a local model approach.
Copolymerization and Cycloaddition Products Derived from Coupling Reactions of 1,2-Epoxy-4-cyclohexene and Carbon Dioxide. Postpolymerization Functionalization via Thiol–Ene Click Reactions (2014)

The coupling reaction of 1,2-epoxy-4-cyclohexene with CO2 in the presence of a ZnCl2/nBu4NI catalyst system was shown to provide the naturally occurring cis-cyclohexadiene carbonate. An alternative synthesis of this compound, which was characterized by X-ray structural analysis, was carried out from the cis-diol and triphosgene. Upon utilizing binary or bifunctional (salen)CrX catalysts, this coupling process resulted in the selective formation of completely alternating copolymer of 1,2-epoxy-4-cyclohexene and carbon dioxide. In the case involving the binary chromium(III)/onium salt catalyst, small quantities of both the cis and trans cyclic carbonates were also produced. The (salen)CoDNP/PPNDNP (DNP = 2,4-dinitrophenolate) catalyst system was most effective at producing high molecular weight copolymer with 100% selectivity. The Tg of this polymer (Mn = 35.9 kDa) was determined to be 123 °C, which is higher than the Tg (116 °C) of the corresponding saturated copolymer. Depolymerization of poly(cyclohexadiene carbonate) to trans-cyclohexadiene carbonate occurred slowly and cleanly at 110 °C following deprotonation of the terminal hydroxyl group. The trans-cyclohexadiene carbonate was independently synthesized via the carbonylation of the trans-diol with ethyl chloroformate. The hydrophobic 1,2-epoxy-4-cyclohexene/CO2 derived copolymer was modified by the quantitative addition of thioglycolic acid by way of the thiol–ene click reaction to afford an amphiphilic copolymer. Upon deprotonation of this functionalized polycarbonate with ammonium hydroxide, the production of a water-soluble polymeric material was achieved which displayed a Tg of 120 °C.
Selection for Thermodynamically Stable DNA Tetraloops Using Temperature Gradient Gel Electrophoresis Reveals Four Motifs:  d(cGNNAg), d(cGNABg), d(cCNNGg), and d(gCNNGc) (2002)

Hairpins play important roles in the function of DNA, forming cruciforms and affecting processes such as replication and recombination. Temperature gradient gel electrophoresis (TGGE) and in vitro selection have been used to isolate thermodynamically stable DNA hairpins from a six-nucleotide random library. The TGGE-selection process was optimized such that known stable DNA tetraloops were recovered, and the selection appears to be exhaustive. In the selection, four families of exceptionally stable DNA loops were identified: d(cGNNAg), d(cGNABg), d(cCNNGg), and d(gCNNGc). (Lowercase denotes the closing base pair; N = A, C, G, or T; and B = C, G, or T.) It appears that the known stable d(cGNAg) triloop motif can be embedded into a tetraloop, with the extra nucleotide inserted into either the middle of the loop, d(cGNNAg), or at the 3'-end of the loop, d(cGNABg). For d(cGNNAg) and d(cGNABg), a CG closing base pair was strongly preferred over a GC, with DeltaDeltaG degrees (37) approximately 2 kcal/mol. Members of the two families, d(cCNNGg) and d(gCNNGc), are similar in stability. The loop sequences and closing base pairs identified for exceptionally stable DNA tetraloops show many similarities to those known for exceptionally stable RNA tetraloops. These data provide an expanded set of thermodynamic rules for the formation of tetraloops in DNA.
Benign Cutaneous Neoplasms in Organ Transplant Recipients (2008)

A wealth of information has been published in recent years concerning the incidence, clinicopathological spectrum, treatment, prognosis, and prevention of skin malignancies in organ transplant recipients (OTRs). However, relatively little has been reported in relation to benign skin tumors. This section will review the available published literature, together with unpublished data, relating to benign tumors observed in our own cohort of over 800 renal transplant recipients under long-term surveillance since 1989 at Bart's and the London NHS Trust, London, U.K (BLT). It should be emphasised that accurate prevalence data are limited for almost all of these tumors, and most published and unpublished observations should therefore be regarded as essentially anecdotal until further data are available from larger cohort studies. Nonetheless, an appreciation of the spectrum of benign tumors in OTRs is important, as some of these tumors may simulate more aggressive malignancies; others represent a source of considerable morbidity, and a few may possess potential for malignant transformation. Relevant published data are summarized in Table 17.1, and particular tumors are discussed in more detail in the following text.