gebhart/patrepeval huggingface dataset:
Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases: Rationale, Biochemistry, Pharmacokinetics, and Outcomes (2018)

Significance: Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine nucleotide that serves as an essential cofactor and substrate for a number of critical cellular processes involved in oxidative phosphorylation and ATP production, DNA repair, epigenetically modulated gene expression, intracellular calcium signaling, and immunological functions. NAD+ depletion may occur in response to either excessive DNA damage due to free radical or ultraviolet attack, resulting in significant poly(ADP-ribose) polymerase (PARP) activation and a high turnover and subsequent depletion of NAD+, and/or chronic immune activation and inflammatory cytokine production resulting in accelerated CD38 activity and decline in NAD+ levels. Recent studies have shown that enhancing NAD+ levels can profoundly reduce oxidative cell damage in catabolic tissue, including the brain. Therefore, promotion of intracellular NAD+ anabolism represents a promising therapeutic strategy for age-associated degenerative diseases in general, and is essential to the effective realization of multiple benefits of healthy sirtuin activity. The kynurenine pathway represents the de novo NAD+ synthesis pathway in mammalian cells. NAD+ can also be produced by the NAD+ salvage pathway. Recent Advances: In this review, we describe and discuss recent insights regarding the efficacy and benefits of the NAD+ precursors, nicotinamide (NAM), nicotinic acid (NA), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN), in attenuating NAD+ decline in degenerative disease states and physiological aging. Critical Issues: Results obtained in recent years have shown that NAD+ precursors can play important protective roles in several diseases. However, in some cases, these precursors may vary in their ability to enhance NAD+ synthesis via their location in the NAD+ anabolic pathway. Increased synthesis of NAD+ promotes protective cell responses, further demonstrating that NAD+ is a regulatory molecule associated with several biochemical pathways. Future Directions: In the next few years, the refinement of personalized therapy for the use of NAD+ precursors and improved detection methodologies allowing the administration of specific NAD+ precursors in the context of patients' NAD+ levels will lead to a better understanding of the therapeutic role of NAD+ precursors in human diseases.
The use of liquid chromatography/thermospray mass spectrometry with on-line ultraviolet diode array and radiochemical detection: Characterization of the putative metabolites of U-78875 in female rat faeces (1994)

The metabolites of an anxiolytic drug candidate U-78875 {3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-5-(1-methylethyl)-imidazo[1,5-α]quinoxalin-4(5H)-one; I} were investigated in female rat faecal extracts following a single oral dose of (14C)I. Initial metabolite profiling was performed by high-performance liquid chromatography incorporating homogeneous (i.e. liquid scintillant added post-column) radiochemical detection (radio-HPLC). This indicated the presence of parent drug and one minor metabolite. Because liquid scintillant is incompatible with thermospray interfaces, subsequent analysis by thermospray/HPLC/MS (TSP/LC/MS) incorporated radiochemical detection in heterogeneous (i.e. solid scintillant) mode and ultraviolet (UV) diode array detection. This revealed that the peak thought previously to be parent drug contained two components: a metabolite (major) and parent drug (minor). The UV spectrum and TSP/LC/MS/MS daughter ion analysis led to the proposition of a bisamide structure for the major metabolite. Chemical synthesis was used to confirm this structure. TSP/LC/MS indicated that the molecular weight of the minor metabolite was 16 u higher than the bisamide, suggesting an oxidized analogue. Attempts to obtain a daughter ion spectrum on this minor metabolite proved unsuccessful. On-line radiochemical and UV diode array detection greatly facilitates the TSP/LC/MS characterization of metabolites from studies using radiolabelled drugs.
Regulation of Blood Pyridoxal Phosphate in Riboflavin Deficiency in Man (1976)

Synthesis and breakdown of pyridoxal phosphate by erythrocytes were studied in subjects with oral lesions before and after treatment with riboflavin. In vivo conversion of pyridoxine to pyridoxal phosphate as well as in vitro synthesis of pyridoxal phosphate by erythrocytes were lower in subjects with lesions of the mouth and improved markedly after treatment with riboflavin. Erythrocyte phosphatase activity, with pyridoxal phosphate as substrate, was lower in riboflavin-deficient subjects and showed an increase after treatment with riboflavin.
A Brief History of Qinghaosu (2015)

The 2015 Nobel Prize for Medicine or Physiology was awarded to William C. Campbell and Satoshi Ōmura for their discovery of avermectins, and to Tu You You for her contribution to the discovery of artemisinin. The discovery and development of qinghaosu (artemisinin) as an antimalarial drug is a remarkable and convoluted tale.
Isolation and expression of an open reading frame encoding sialidase from Trypanosoma rangeli (1996)

Several protozoan parasites of human have been found to express enzymes capable of releasing terminal sialic acid residues from host glycans. These include enzymes similar in activity to bacterial and viral sialidases, as well as a novel type of enzyme, trans-sialidase, which can transfer sialic acid from one carbohydrate chain to another. Here we report the isolation of a gene and a gene fragment from the kinetoplastid Trypanosoma rangeli which encode products related in sequence to the trans-sialidase enzyme of T. cruzi. The gene fragment ORF is nearly identical to that of the complete gene, which encodes an enzymatically inactive protein. When the ORF of the gene fragment is fused to fragments from related genes, it encodes a product with sialidase activity. Both predicted T. rangeli protein products also have other potential structural features found in bacterial sialidases and in members of a previously described Trypanosoma trans-sialidase superfamily.
Theocritus' <i>Adoniazusae</i> (1995)

Theocritus' poem on the women celebrating the festival of Adonis ( Idyll 15) has received surprisingly little attention over the years, especially when compared with other Theocritean Idylls of like length. Matthew Arnold's notorious rhapsody (‘a page torn fresh out of the book of human life. What freedom! What animation! What gaiety! What naturalness! … When such is Greek poetry of the decadence, what must be Greek poetry of the prime?’) has perhaps done more harm than good, by focusing attention too exclusively on the first hundred lines or so of the poem (and indeed Arnold himself was of the opinion that the hymn to Adonis at vv. 100ff. contains ‘of religious emotion, in our acceptation of the words, and of the comfort springing from religious emotion, not a particle’). And yet the poem is second only to Euripides' Bacchae as a document revealing the ways in which religion in the ancient Greek world could offer women an escape (however temporary) from the drab banalities of their everyday existence. And the central contrast between the eternal and idealized glamour of the world of myth and the time-bound existence of Praxinoa and Gorgo (a contrast which is crucial for the above-mentioned role of religion) is absolutely characteristic of one essential aspect of Hellenistic poetry, an aspect that looks back to the world of Euripides and forward to that of Roman poets like Catullus or Propertius. In this paper I shall examine both these features of the Idyll. Also, inspired by those scholars who have illuminated facets of the Dionysiac religion by adducing comparable (if secular) twentieth-century material, I shall try to achieve something similar for Theocritus' poem by drawing on comparative material from late twentieth-century Japan relating to a phenomenon that allows Japanese housewives temporary escape from a tedious and restricted way of life.
A hybrid anaerobic solid–liquid system for food waste digestion (2005)

A hybrid anaerobic solid - liquid (HASL) system was developed to enhance food waste bioconversion in comparison with the conventional two-phase anaerobic digester. The advantages of the HASL system were the higher efficiency of methane production and smaller volume of effluent from the system. The biogas, which was generated from the methanogenic phase, had an average methane content of 71-72%. Total removal of volatile solids consisted of 78-80%. The HASL system can be operated in both batch and semi-continuous modes with satisfactory performance. The addition of a submerged biofilter for ammonia removal to the HASL system further enhanced the performance of anaerobic digestion. Methane production in the enhanced HASL system was increased by 26% in comparison with the HASL system without submerged filter. This paper describes the development of the enhanced HASL system for anaerobic treatment of food waste.
Absence of <i>Porphyromonas asaccharolytica, Bacteroides fragilis</i> and <i>Chlamydia pneumoniae</i> in human subgingival plaque (1997)

Little is known about the presence of common medical pathogens in the human oral cavity. Using a 16S rRNA-based PCR identification method, this study determined the occurrence of Porphyromonas asaccharolytica, Bacteroides fragilis and Chlamydia pneumoniae in subgingival plaque from 50 adults with advanced periodontitis. Each patient contributed samples from 3 deep periodontal pockets collected by paper points. The PCR primers were for P. asaccharolytica 5'-CTC TAG CTA GAG TGT ACT GG-3' and 5'-ATA GGG TTT ATA GAT TAG CTC TCT-3', for B. fragilis 5'-AAT GAT TCC GCA TGG TTT CAT TA-3' and 5'-GCG GTG ATT GCT CAC TGA CA-3', and for C. pneumoniae 5'- TGA CAA CTG TAG AAA TAC AGC-3' and 5'-CGC CTC TCT CCT ATA AAT-3'. The primers yielded a single amplicon with the respective reference strains and produced no amplicon with colonies of 25 groups of oral organisms. None of the three test species were detected in any of the 50 pooled subgingival samples tested. P. asaccharyolytica, B. fragilis and C. pneumoniae do not seem to be part of the periodontopathic microbiota in humans.
Lafora bodies and neurological defects in malin-deficient mice correlate with impaired autophagy (2011)

Lafora disease (LD), a fatal neurodegenerative disorder characterized by the presence of intracellular inclusions called Lafora bodies (LBs), is caused by loss-of-function mutations in laforin or malin. Previous studies suggested a role of these proteins in the regulation of glycogen biosynthesis, in glycogen dephosphorylation and in the modulation of the intracellular proteolytic systems. However, the contribution of each of these processes to LD pathogenesis is unclear. We have generated a malin-deficient (Epm2b-/-) mouse with a phenotype similar to that of LD patients. By 3-6 months of age, Epm2b-/- mice present neurological and behavioral abnormalities that correlate with a massive presence of LBs in the cortex, hippocampus and cerebellum. Sixteen-day-old Epm2b-/- mice, without detectable LBs, show an impairment of macroautophagy (hereafter called autophagy), which remains compromised in adult animals. These data demonstrate similarities between the Epm2a-/- and Epm2b-/- mice that provide further insights into LD pathogenesis. They illustrate that the dysfunction of autophagy is a consequence of the lack of laforin-malin complexes and a common feature of both mouse models of LD. Because this dysfunction precedes other pathological manifestations, we propose that decreased autophagy plays a primary role in the formation of LBs and it is critical in LD pathogenesis.
Different Mechanisms for Ca Dissociation from Complexes of Calmodulin with Nitric Oxide Synthase or Myosin Light Chain Kinase (1996)

We have determined the stoichiometry and rate constants for the dissociation of Ca2+ ion from calmodulin (CaM) complexes with rabbit skeletal muscle myosin light chain kinase (skMLCK), rat brain nitric oxide synthase (nNOS) or with the respective peptides (skPEP and nPEP) representing the CaM-binding domains in these enzymes. Ca2+ dissociation kinetics determined by stopped-flow fluorescence using the Ca2+ chelator quin-2 MF are as follows. 1) Two sites in the CaM-nNOS and CaM-nPEP complexes have a rate constant of 1 s-1. 2) The remaining two sites have a rate constant of 18 s-1 for CaM-nPEP and > 1000 s-1 for CaM-nNOS. 3) Three sites have a rate constant of 1.6 s-1 for CaM-skMLCK and 0.15 s-1 for CaM-skPEP. 4) The remaining site has a rate constant of 2 s-1 for CaM-skPEP and > 1000 s-1 for CaM-skMLCK. Comparison of these rate constants with those determined for complexes between the peptides and tryptic fragments representing the C- or N-terminal lobes of CaM indicate a mechanism for Ca2+ dissociation from CaM-nNOS of 2C slow + 2N fast and from CaM-skMLCK of (2C + 1N) slow + 1N fast. Ca2+ removal inactivates CaM-nNOS and CaM-skMLCK activities with respective rate constants of > 10 s-1 and 1 s-1. CaM-nNOS inactivation is fit by a model in which rapid Ca2+ dissociation from the N-terminal lobe of CaM is coupled to enzyme inactivation and slower Ca2+ dissociation from the C-terminal lobe is coupled to dissociation of the CaM-nNOS complex. CaM-skMLCK inactivation is fit by a model in which the three slowly dissociating Ca(2+)-binding sites are coupled to both dissociation of the complex and enzyme inactivation.
Characterization of the Transport Mechanism and Permeant Binding Profile of the Uridine Permease Fui1p of Saccharomyces cerevisiae (2006)

The uptake of Urd into the yeast Saccharomyces cerevisiae is mediated by Fui1p, a Urd-specific nucleoside transporter encoded by the FUI1 gene and a member of the yeast Fur permease family, which also includes the uracil, allantoin, and thiamine permeases. When Fui1p was produced in a double-permease knock-out strain (fur4Deltafui1Delta) of yeast, Urd uptake was stimulated at acidic pH and sensitive to the protonophore carbonyl cyanide m-chlorophenylhydrazone. Electrophysiological analysis of recombinant Fui1p produced in Xenopus oocytes demonstrated that Fui1p-mediated Urd uptake was dependent on proton cotransport with a 1:1 stoichiometry. Mutagenesis analysis of three charged amino acids (Glu(259), Lys(288), and Asp(474) in putative transmembrane segments 3, 4, and 7, respectively) revealed that only Lys(288) was required for maintaining high Urd transport efficiency. Analysis of binding energies between Fui1p and different Urd analogs indicated that Fuip1 interacted with C(3')-OH, C(2')-OH, C(5)-H, and N(3)-H of Urd. Fui1p-mediated transport of Urd was inhibited by analogs with modifications at C-5', but was not inhibited significantly by analogs with modifications at C-3', C-5, and N-3 or inversions of configuration at C-2' and C-3'. This characterization of Fui1p contributes to the emerging knowledge of the structure and function of the Fur family of permeases, including the Fui1p orthologs of pathogenic fungi.
Glycosyltransferases and their Assays (2010)

Glycosyltransferases (GTs) are a large family of enzymes that are essential in all domains of life for the biosynthesis of complex carbohydrates and glycoconjugates. GTs catalyse the transfer of a sugar from a glycosyl donor to a variety of acceptor molecules, for example, oligosaccharides, peptides, lipids or small molecules. Such glycosylation reactions are central to many fundamental biological processes, including cellular adhesion, cell signalling and bacterial- and plant-cell-wall biosynthesis. GTs are therefore of significant interest as molecular targets in chemical biology and drug discovery. In addition, GTs have found wide application as synthetic tools for the preparation of complex carbohydrates and glycoconjugates. In order to exploit the potential of GTs both as molecular targets and synthetic tools, robust and operationally simple bioassays are essential, especially as more and more protein sequences with putative GT activity but unknown biochemical function are being identified. In this minireview, we give a brief introduction to GT biochemistry and biology. We outline the relevance of GTs for medicinal chemistry and chemical biology, and describe selected examples for recently developed GT bioassays, with a particular emphasis on fluorescence-based formats.
The genetic epidemiology of neurodegenerative disease (2005)

Gene defects play a major role in the pathogenesis of degenerative disorders of the nervous system. In fact, it has been the very knowledge gained from genetic studies that has allowed the elucidation of the molecular mechanisms underlying the etiology and pathogenesis of many neurodegenerative disorders. In this review, we discuss the current status of genetic epidemiology of the most common neurodegenerative diseases: Alzheimer disease, Parkinson disease, Lewy body dementia, frontotemporal dementia, amyotrophic lateral sclerosis, Huntington disease, and prion diseases, with a particular focus on similarities and differences among these syndromes.
Sidelobe suppression for OFDM based cognitive radio systems (2009)

This paper investigates the sidelobe suppression techniques of Orthogonal Frequency Division Multiplexing (OFDM) based Cognitive Radio (CR) systems. We firstly argue that the existing sidelobe suppression algorithms cannot satisfy the special requirements of CR systems. Then we formulate the interference suppression problem of CR systems into two algorithms from capacity perspective, namely, average power allocation with cancellation subcarrier (CCs) scheme and adaptive subcarrier weighting scheme. We show that the capacity of the two schemes can well approximate the ideal waterfilling algorithm performance. We further show that under tough interference suppression requirement of licensed users (LU), the adaptive subcarrier weighting scheme is a better choice for CR systems.
1,4-Addition of (Diphenylmethylene)amine to Acceptor Substituted Olefins. A Versatile Synthesis of Protected β-Amino Acids, Nitriles, and Ketones (1989)

(Diphenylmethylene)amine [benzophenone imine, DPMA-H] cleanly reacts with a variety of α,β-unsaturated esters, nitriles, ketones, and aldehydes 1a-q to give Michael type adducts 2a-q, generally, in respectable to excellent yields. Sterically congested and donor-substituted Michael acceptors do not react. The β-amino-substituted products can be further transformed in their protected form, or selectively deprotected under mild conditions, e.g. by catalytic hydrogenation.
Real-Time Price-Based Demand Response Management for Residential Appliances via Stochastic Optimization and Robust Optimization (2012)

This paper evaluates the real-time price-based demand response (DR) management for residential appliances via stochastic optimization and robust optimization approaches. The proposed real-time price-based DR management application can be imbedded into smart meters and automatically executed on-line for determining the optimal operation of residential appliances within 5-minute time slots while considering uncertainties in real-time electricity prices. Operation tasks of residential appliances are categorized into deferrable/non-deferrable and interruptible/non-interruptible ones based on appliances' DR preferences as well as their distinct spatial and temporal operation characteristics. The stochastic optimization adopts the scenario-based approach via Monte Carlo (MC) simulation for minimizing the expected electricity payment for the entire day, while controlling the financial risks associated with real-time electricity price uncertainties via the expected downside risks formulation. Price uncertainty intervals are considered in the robust optimization for minimizing the worst-case electricity payment while flexibly adjusting the solution robustness. Both approaches are formulated as mixed-integer linear programming (MILP) problems and solved by state-of-the-art MILP solvers. The numerical results show attributes of the two approaches for solving the real-time optimal DR management problem for residential appliances.
The calculating PHM cluster: CH&amp;P mathematical models and algorithms of early prognosis of failure (2012)

This work describes mathematical models and computing cluster for early failure prognosis and accurate estimates of remaining useful life (RUL) for technical objects: internal combustion engines, gas turbine, hydroelectric turbines, wind turbines, etc. The hierarchy of mathematical models for prognosis (CH&P) is based on a hierarchy of degrees of developed failure, and solves the problem of accurate assessment of RUL; determines the required physical parameters for the prediction and risk assessment; classifies the signs and their evolution at all stages of development. In the absence of early incipient fault the mathematical model identifies incipient of fault cause, the time evolution of which leads to the appearance of early incipient fault. In the absence of incipient of fault cause the hierarchical mathematical model analyzes the state of the system using the methods of symbolic and topological dynamics to identify the evolution of symbolic hidden trajectories of the observed signals, which leads to Incipient of hidden fault cause. Thus, the hierarchical mathematical model provides the earliest prognosis of occurrence of failure causes. It is also noted that in the analysis stage of hidden trajectories (preventive prognosis) is possible a physical reversibility in the technical system. There is a legitimate question about the implementation of the automatic stochastic management by system in real time in order to avoid failure at the stage of the appearance of their hidden causes.
Improved Accuracy and Precision In Simultaneous Myocardial T1 and T2 mapping with Multi-Parametric SASHA (mSASHA) (2021)

Purpose: To develop and validate a multi-parametric SAturation-recovery single-SHot Acquisition (mSASHA) cardiac T1 and T2 mapping technique with high accuracy and precision in a single breath-hold. Methods: The mSASHA acquisition consists of 9 images in an 11 heartbeat breath-hold -- the first without preparation, 6 images with saturation recovery preparation, and 2 images with both saturation recovery and T2-preparation. T1 and T2 values were calculated using a 3-parameter model. mSASHA was validated in simulations and phantoms on a Siemens 3T Prisma scanner with comparison to a joint T1-T2 technique with a 4-parameter model. mSASHA values were compared to reference MOLLI, SASHA and T2p-bSSFP sequences in 10 healthy volunteers. Results: mSASHA had high accuracy compared to reference spin-echo measurements, with an average of -0.7+/-0.4% T1 error and -1.3+/-1.3% T2 error. mSASHA coefficient of variation (CoV) in phantoms for T1 was lower than MOLLI (0.7+/-0.1% vs 0.9+/-0.2%, p<0.01) and similar to reference T2p-bSSFP for T2 (1.4+/-0.6% vs 1.5+/-0.5%, p>0.05). In simulations, 3-parameter mSASHA fitting had higher precision than 4-parameter joint T1-T2 fitting for both T1 and T2. In-vivo myocardial mSASHA T1 was similar to conventional SASHA (1523+/-18 ms vs 1520+/-18 ms, p>0.05) with similar CoV to both MOLLI and SASHA (3.3+/-0.6% vs 3.1+/-0.6% and 3.3+/-0.5% respectively, p>0.05 for both). Myocardial mSASHA T2 values were 37.1+/-1.1 ms with similar precision to T2p-bSSFP (6.7+/-1.7% vs 6.0+/-1.6%, p>0.05). Conclusion: mSASHA provides high accuracy cardiac T1 and T2 quantification in a single breath-hold, with similar precision to reference MOLLI and linear T2p-bSSFP reference techniques.