gebhart/patrepeval huggingface dataset:
Mechanism of Nicotinamide Inhibition and Transglycosidation by Sir2 Histone/Protein Deacetylases (2003)

Silent information regulator 2 (Sir2) enzymes catalyze NAD+-dependent protein/histone deacetylation, where the acetyl group from the lysine epsilon-amino group is transferred to the ADP-ribose moiety of NAD+, producing nicotinamide and the novel metabolite O-acetyl-ADP-ribose. Sir2 proteins have been shown to regulate gene silencing, metabolic enzymes, and life span. Recently, nicotinamide has been implicated as a direct negative regulator of cellular Sir2 function; however, the mechanism of nicotinamide inhibition was not established. Sir2 enzymes are multifunctional in that the deacetylase reaction involves the cleavage of the nicotinamide-ribosyl, cleavage of an amide bond, and transfer of the acetyl group ultimately to the 2'-ribose hydroxyl of ADP-ribose. Here we demonstrate that nicotinamide inhibition is the result of nicotinamide intercepting an ADP-ribosyl-enzyme-acetyl peptide intermediate with regeneration of NAD+ (transglycosidation). The cellular implications are discussed. A variety of 3-substituted pyridines was found to be substrates for enzyme-catalyzed transglycosidation. A Brönsted plot of the data yielded a slope of +0.98, consistent with the development of a nearly full positive charge in the transition state, and with basicity of the attacking nucleophile as a strong predictor of reactivity. NAD+ analogues including beta-2'-deoxy-2'-fluororibo-NAD+ and a His-to-Ala mutant were used to probe the mechanism of nicotinamide-ribosyl cleavage and acetyl group transfer. We demonstrate that nicotinamide-ribosyl cleavage is distinct from acetyl group transfer to the 2'-OH ribose. The observed enzyme-catalyzed formation of a labile 1'-acetylated-ADP-fluororibose intermediate using beta-2'-deoxy-2'-fluororibo-NAD+ supports a mechanism where, after nicotinamide-ribosyl cleavage, the carbonyl oxygen of acetylated substrate attacks the C-1' ribose to form an initial iminium adduct.
Studies in fat metabolism in the fowl (1934)

THE study of the formation and utilisation of fat in the fowl is of fundamental interest, since our knowledge of these processes in the bird is very meagre, investigations of fat metabolism having been so far carried out almost ex- clusively on mammals. With a view to eliciting information along these lines it was decided to investigate two problems which presented themselves as being of primary importance to the poultry industry. (1) The approximate com- position of the mixed fatty acids of the normal egg and the extent to which this may be modified by the inclusion of fat in the ration. (2) The influence of ingested fat on the composition of the depot fat. The latter investigation is of a preliminary nature.
Apoptosis in the human uterine endometrium during the menstrual cycle. (1996)

To investigate apoptotic changes, we studied the cleavage of DNA in the uterine endometrium obtained from regularly cycling women by a quantitative end labeling of DNA gel fractionation and in situ analysis. The ladder pattern characteristic of the apoptotic cleavage of DNA into fragments of low mol wt was identified at three different phases of the cycle, namely the early proliferative, late secretory, and menstrual phases. However, DNA of high mol wt was predominant in the endometrium during the late proliferative, early secretory, and midsecretory phases. Our analysis in situ revealed that cells undergoing apoptosis were scattered in the functional layer of the early proliferative endometrium. However, apoptotic cells were no longer detectable during the late proliferative phase, and none was observed until the midsecretory phase. At the beginning of the late secretory phase, apoptosis reappeared in the stromal cells and spread gradually to almost all components of the functional layer. By contrast, cells in the basal layer showed no evidence of apoptosis throughout the menstrual cycle. The present study demonstrates that apoptosis occurs in specific populations of cells during three phases of the human endometrial cycle. Our results indicate, moreover, that apoptosis might have an important role in the regulation of the menstrual cycle in women.
The DC‐HIL/syndecan‐4 pathway inhibits human allogeneic T‐cell responses (2009)

T-cell activation is regulated by binding of ligands on APC to corresponding receptors on T cells. In mice, we discovered that binding of DC-HIL on APC to syndecan-4 (SD-4) on activated T cells potently inhibits T-cell activation. In humans, we now show that DC-HIL also binds to SD-4 on activated T cells through recognition of its heparinase-sensitive saccharide moiety. DC-HIL blocks anti-CD3-induced T-cell responses, reducing secretion of pro-inflammatory cytokines and blocking entry into the S phase of the cell cycle. Binding of DC-HIL phosphorylates SD-4's intracellular tyrosine and serine residues. Anti-SD-4 Ab mimics the ability of DC-HIL to attenuate anti-CD3 response more potently than Ab directed against other inhibitory receptors (CTLA-4 or programmed cell death-1). Among leukocytes, DC-HIL is expressed highest by CD14(+) monocytes and this expression can be upregulated markedly by TGF-beta. Among APC, DC-HIL is expressed highest by epidermal Langerhans cells, an immature type of dendritic cells. Finally, the level of DC-HIL expression on CD14(+) monocytes correlates inversely with allostimulatory capacity, such that treatment with TGF-beta reduced this capacity, whereas knocking down the DC-HIL gene augmented it. Our findings indicate that the DC-HIL/SD-4 pathway can be manipulated to treat T-cell-driven disorders in humans.
Increased osteoblast adhesion on titanium‐coated hydroxylapatite that forms CaTiO<sub>3</sub> (2003)

CaTiO(3) is a strong candidate to form at the interface between hydroxylapatite (HA) and titanium implants during many coating procedures. However, few studies have compared the cytocompatibility properties of CaTiO(3) to HA pertinent for bone-cell function. For this reason, the objective of the present in vitro study was to determine the ability of bone-forming cells (osteoblasts) to adhere on titanium coated with HA that resulted in the formation of CaTiO(3). To accomplish the formation of CaTiO(3), titanium was coated on HA discs and annealed either under air or a N(2)+H(2) environment. Materials were characterized by X-ray diffraction (XRD), Rutherford backscattering spectroscopy (RBS), and atomic force microscopy (AFM). These characterization techniques demonstrated the formation of a nanometer rough CaTiO(3) layer as a consequence of interactions between HA and titanium during coating conditions. Results from cytocompatibility tests revealed increased osteoblast adhesion on materials that contained CaTiO(3) compared to both pure HA and uncoated titanium. The greatest osteoblast adhesion was observed on titanium-coated HA annealed under air conditions. Because adhesion is a crucial prerequisite to subsequent functions of osteoblasts (such as the deposition of calcium containing mineral), the present in vitro results imply that orthopedic coatings that form CaTiO(3) could increase osseointegration with juxtaposed bone needed for increased implant efficacy.
Virtual Fabrication of Steel Welded Plate Girders (2009)

During the fabrication of plate girders undesirable stresses and deformations develop mainly as a result of uneven temperature distributions. These stresses and deformations (imperfections) may significantly affect the performance (e.g. ultimate strength or fatigue life) of the structure. In the research described in this paper an effective numerical method to predict these imperfections is developed with the objective of incorporating this knowledge into the design procedures. This paper presents the background of the research including the difficulties in numerical welding simulation, the numerical solution strategy and the current state of the development illustrated with examples.
Studies on the µ-(NN′)-ethylenediaminetetra-acetato-di-µ-oxo-bis-[oxotungstate(<scp>V</scp>)], [W<sub>2</sub>O<sub>4</sub>(edta)]<sup>2–</sup>, complex in aqueous solutions. Formation of an aquo-ion and redox properties (1980)

The aquation of [W2O4(edta)]2–(edta = ethylenediaminetetra-acetate) to W2O42+(or a closely related species) proceeds to completion in HCl 2 mol dm–3. First-order kinetics have been observed, with the rate constant (1.16 × 10–4 s–1 at 25 °C) in 2 mol dm–3 HCl some 60 times less than for the corresponding reaction of [Mo2O4(edta)]2–. With HClO4 2 mol dm–3 aquation is accompanied by oxidation to WVI. No aquation (or oxidation) has been observed with HClO4 < 0.5 mol dm–3, under which condition redox reactions of the edta complex could be investigated. At 25 °C, I= 0.50 mol dm–3(H–LiClO4) rate constants for the first stage of the 1 : 2 oxidations of [W2O4(edta)]2– with [IrCl6]2– and [Fe(phen)3]3+(phen = 1,10-phenanthroline) are 6.3 × 105 dm3 mol–1 s–1 and >107 dm3 mol–1 s–1 respectively. For the [IrCl6]2– reaction activation parameters are ΔH‡= 5.4 kcal mol–1 and ΔS‡=–13.8 cal K–1 mol–1 respectively. Rate constants (dm3 mol–1 s–1) for other oxidants, I= 0.10 mol dm–3, are [Fe(CN)6]3–(0.058), [Co(bipy)3]3+(2.0)(bipy = 2,2′-bipyridine), and I3–(ca. 20). The complex [W2O4(edta)]2– is a much stronger reducing agent than [Mo2O4(edta)]2–.
Alternative methods for production of alicyclic epoxides (2014)

The salient and peculiar features of the oxidation of dicyclopentene and unsaturated alicyclic hydrocarbons with a medium-sized carbon ring into the corresponding epoxides have been studied. Organic hydroperoxides, aqueous hydrogen peroxide, and peracids have been used as oxidizing agents. The reactivity of the substrates in each of the oxidation processes under consideration has been estimated, and conditions providing a high epoxide yield have been chosen. The advantages and disadvantages of each process taking into account the problems of isolation of the desired product are considered. The results obtained allow the peracid method to be recommended for the synthesis of dicyclopentene epoxide as an effective and convenient for practical implementation.
Assessing Crowdsourced POI Quality: Combining Methods Based on Reference Data, History, and Spatial Relations (2017)

With the development of location-aware devices and the success and high use of Web 2.0 techniques, citizens are able to act as sensors by contributing geographic information. In this context, data quality is an important aspect that should be taken into account when using this source of data for different purposes. The goal of the paper is to analyze the quality of crowdsourced data and to study its evolution over time. We propose two types of approaches: (1) use the intrinsic characteristics of the crowdsourced datasets; or (2) evaluate crowdsourced Points of Interest (POIs) using external datasets (i.e., authoritative reference or other crowdsourced datasets), and two different methods for each approach. The potential of the combination of these approaches is then demonstrated, to overcome the limitations associated with each individual method. In this paper, we focus on POIs and places coming from the very successful crowdsourcing project: OpenStreetMap. The results show that the proposed approaches are complementary in assessing data quality. The positive results obtained for data matching show that the analysis of data quality through automatic data matching is possible but considerable effort and attention are needed for schema matching given the heterogeneity of OSM and the representation of authoritative datasets. For the features studied, it can be noted that change over time is sometimes due to disagreements between contributors, but in most cases the change improves the quality of the data.
ADAM33: a novel therapeutic target for asthma (2003)

The incidence of asthma worldwide is increasing, and the disease has a large unmet clinical need. Despite the availability of anti-inflammatory and bronchodilator medication, there is persisting morbidity and mortality. New approaches are needed to understand the role that structural changes in the airways (remodelling) play in this process. Studies of the genetic basis of asthma have identified the ADAM33 (a disintegrase and metalloproteinase 33) gene, a novel member of the ADAM family of zinc-dependent metalloproteases, as a risk factor for the development of asthma and bronchial hyperresponsiveness (BHR). The identification of ADAM33 as a major risk factor involved in the pathogenesis of BHR and airway wall remodelling provides insight into the pathogenesis of asthma and represents a novel therapeutic target.
Stimulated emission of near-infrared radiation by current injection into silicon (100) quantum well (2009)

We describe the observation of stimulated emissions by current injections into a silicon quantum well. The device consists of a free standing membrane with a distributed feedback resonant cavity fabricated by state-of-the-art silicon processes. The emission spectra have multimode structures peaked in the near-infrared region above the submilliampere threshold currents at room temperatures. Consequently, electronics and photonics should be able to be converged on chips by using silicon quantum well laser diodes.
Novel DNA sensor system for highly sensitive and quantitative retrovirus detection using virus encoded integrase as a biomarker (2016)

In the current study we describe a novel DNA sensor system that allows the detection of single catalytic DNA integration events mediated by retrovirus encoded integrase (IN) present in viral particles. This is achieved by rolling circle amplification mediated conversion of enzymatic reactions happening within nanometer dimensions to directly detectable micrometer sized DNA products. The system utilizes the unique integration reaction of IN to generate a surface anchored nicked DNA circle that serves as a substrate for rolling circle amplification and allows for specific, quantitative and sensitive detection of purified recombinant IN or virus particles with a detection limit of less than 30 virus particles per μL of sample. Moreover, by modifying the nucleotide sequences of the utilized DNA it was possible to tailor the system to distinguish between the highly pathogenic lentivirus HIV and the gammaretrovirus murine leukemia virus present in a given sample. Infections with HIV remain a major threat to global health with more than 2 million new infections and 1 million deaths each year. The sensitive and specific detection of HIV particles based on IN activity holds promise for the development of a new type of diagnostic tools suitable for early (within hours of infection) detection of HIV, which would be valuable for prevention strategies as well as for efficient treatment.
Stop codons preceded by rare arginine codons are efficient determinants of SsrA tagging in <i>Escherichia coli</i> (2002)

The SsrA or tmRNA quality control system intervenes when ribosomes stall on mRNAs and directs the addition of a C-terminal peptide tag that targets the modified polypeptide for degradation. Although hundreds of SsrA-tagged proteins can be detected in cells when degradation is prevented, most of these species have not been identified. Consequently, the mRNA sequence determinants that cause ribosome stalling and SsrA tagging are poorly understood. SsrA tagging of Escherichia coli ribokinase occurs at three specific sites at or near the C terminus of this protein. The sites of tagging correspond to ribosome stalling at the termination codon and at rare AGG codons encoding Arg-307 and Arg-309, the antepenultimate and C-terminal residues of E. coli ribokinase. Mutational analyses and studies of the effects of overexpressing the tRNA that decodes AGG reveal that the combination of a rare arginine codon at the C terminus and the adjacent inefficient UGA termination codon act to recruit the SsrA-tagging system, presumably by slowing the rate of translation elongation and termination.
On the Microstructure of Nanoporous Gold: An X-ray Diffraction Study (2009)

The evolution of the grain structure, internal strain, and the lattice misorientations of nanoporous gold during dealloying of bulk (3D) Ag-Au alloy samples was studied by various in situ and ex situ X-ray diffraction techniques including powder and Laue diffraction. The experiments reveal that the dealloying process preserves the original crystallographic structure but leads to a small spread in orientations within individual grains. Initially, most grains develop in-plane tensile stresses, which are partly released during further dealloying. Simultaneously, the feature size of the developing nanoporous structure increases with increasing dealloying time. Finally, microdiffraction experiments on dealloyed micron-sized nanoporous pillars reveal significant surface damage introduced by focused ion beam milling.
Deterministic model to evaluate the impact of lactational treatment of subclinical mastitis due to coagulase-negative staphylococci (2011)

Coagulase-negative staphylococci (CNS) are the most frequently isolated bacteria from milk samples in several studies worldwide. Despite their relative frequency, specific measures aiming at their control are not well established. One possible measure to include in a control programme is lactational antimicrobial treatment. The decision to perform such treatment, as well as other actions on farm, should be based on the likelihood of financial return. A deterministic model was used to evaluate whether performing an antimicrobial treatment during the lactation for quarters infected with CNS was financially justifiable. Input variables for the impact of CNS on udder health were based on a previous study by the same authors and on available literature on the subject. Prices included in the model were based on 2009/2010 conditions in Portugal. The average result per antimicrobial treated quarter was a net loss of €38·74. Performing a sensitivity analysis to evaluate how systematic variation of the input variables of the model would lead to outcome changes showed that variation in input variables nearly always led to a negative outcome, with the greatest variation in losses observed for variation in the length of treatment and milk withdrawal period (-€46·26 to -€28·49). The situations in which a net benefit was to be expected included the bulk tank somatic cell count decreasing to a level corresponding to a premium payment or to penalties being avoided, and the prevention of transmission of CNS in the milking parlour when the possibility of transmission was at its highest level. For most situations, lactational treatment of CNS subclinical mastitis was not financially justifiable.
Femtosecond to Millisecond Dynamics of Light Induced Allostery in the <i>Avena sativa</i> LOV Domain (2017)

The rational engineering of photosensor proteins underpins the field of optogenetics, in which light is used for spatiotemporal control of cell signaling. Optogenetic elements function by converting electronic excitation of an embedded chromophore into structural changes on the microseconds to seconds time scale, which then modulate the activity of output domains responsible for biological signaling. Using time-resolved vibrational spectroscopy coupled with isotope labeling, we have mapped the structural evolution of the LOV2 domain of the flavin binding phototropin Avena sativa (AsLOV2) over 10 decades of time, reporting structural dynamics between 100 fs and 1 ms after optical excitation. The transient vibrational spectra contain contributions from both the flavin chromophore and the surrounding protein matrix. These contributions are resolved and assigned through the study of four different isotopically labeled samples. High signal-to-noise data permit the detailed analysis of kinetics associated with the light activated structural evolution. A pathway for the photocycle consistent with the data is proposed. The earliest events occur in the flavin binding pocket, where a subpicosecond perturbation of the protein matrix occurs. In this perturbed environment, the previously characterized reaction between triplet state isoalloxazine and an adjacent cysteine leads to formation of the adduct state; this step is shown to exhibit dispersive kinetics. This reaction promotes coupling of the optical excitation to successive time-dependent structural changes, initially in the β-sheet and then α-helix regions of the AsLOV2 domain, which ultimately gives rise to Jα-helix unfolding, yielding the signaling state. This model is tested through point mutagenesis, elucidating in particular the key mediating role played by Q513.
Oxidation of Alkanes with Dioxygen Induced by Visible Light and Cu(II) and Fe(III) Chlorides (2003)

Abstract Cyclohexane and adamantane were oxidized in acetonitrile with dioxygen to the corresponding alcohols and ketones under irradiation of visible light in the presence of CuCl2 or FeCl3 catalyst. Fairly good selectivity of the products was attained with CuCl2: ca. 50% for cyclohexane and 75% for adamantane at over 50% conversion. Alkyl hydroperoxides were detected during the reactions in 10% and 25% amounts of the products at maximum for the cyclohexane oxidation with CuCl2 and FeCl3, respectively. Moreover, the products were overoxidized by the present system at comparable or slower rates than the alkanes. Other features of the reaction, such as the rate of oxygen uptake and carbon dioxide liberation, isotope effect, and radical inhibitor effect, were also investigated.
Integration and synchronization of discrete formalisms and continuous models in Modelica (2003)

Many complex technical systems such as airplanes or chemical plants consist of hybrid physical components and purely discrete controllers. In order to aid the design process of such systems, some requirements have to be met as closely as possible: the hybrid physical and the discrete components have to be modeled vividly, the resulting components of the model have to be integrated intuitively into a complete model, and this model has to be simulated efficiently. Numerical integration and discrete-event simulation have to be synchronized. We discuss how the object-oriented modeling language Modelica meets these requirements.
Vertical Cavity Lasers for Atomic Time Standards (1999)

The availability of Vertical Cavity Lasers (VCSELs) has allowed the development of new generations of optical systems, which can benefit from the small size, low power consumption, and high reliability of these light sources. Among diode laser families, VCSELs are particularly attractive for a number of reasons: (I) relatively simple and robust fabrication; (2) very low threshold current and, thus, low power consumption; (3) surface emission, thus simplified packaging and two-dimensional array capabilities; (4) circular emission apertures and, thus, good beam shape in the near and far-field; and (5) single-mode emission with a high wavelength tuning rate and range. Rubidium- or cesium-based atomic time standards could benefit greatly from the use of customized VCSELs as a pump for Rb or Cs. Required is a high spectral purity coupled with emission at precisely the pump wavelengths of interest: 780 or 852 nm. The Swiss Center for Electronics and Microtechnology (CSEM) has developed VCSELs for atomic time standard applications, which fulfill these requirements, and is preparing their industrialization. Optimized laser parameters include single-mode emission with a high side-mode suppression ratio, polarization stability, narrow linewidth, high tunability, and low noise. In this paper, we will discuss the principles underlying VCSEL operation, the required fabrication technology, and, finally, the electro-optical characteristics as these relate to the use of VCSELs in atomic clocks. We will present device results on 780 nm VCSELs customized for operation at elevated temperatures for use in Rb time standards. An emphasis will be placed on spectral properties, tunability, and stability. Based on these developments, it is expected that VCSELs may soon play a significant role in a new generation of compact atomic time standards.