gebhart/patrepeval huggingface dataset:
Nicotinamide riboside activates SIRT5 deacetylation (2023)

Human sirtuins play important roles in various cellular events including DNA repair, gene silencing, mitochondrial biogenesis, insulin secretion and apoptosis. They regulate a wide array of protein and enzyme targets through their NAD<sup>+</sup> -dependent deacetylase activities. Sirtuins are also thought to mediate the beneficial effects of low-calorie intake to extend longevity in diverse organisms from yeast to mammals. Small molecules mimicking calorie restriction to stimulate sirtuin activity are attractive therapeutics against age-related disorders such as cardiovascular diseases, diabetes and neurodegeneration. Little is known about one of the mitochondrial sirtuins, SIRT5. SIRT5 has emerged as a critical player in maintaining cardiac health and neuronal viability upon stress and functions as a tumour suppressor in a context-specific manner. Much has been debated about whether SIRT5 has evolved away from being a deacetylase because of its weak catalytic activity, especially in the in vitro testing. We have, for the first time, identified a SIRT5-selective allosteric activator, nicotinamide riboside (NR). It can increase SIRT5 catalytic efficiency with different synthetic peptide substrates. The mechanism of action was further explored using a combination of molecular biology and biochemical strategies. Based on the existing structural biology information, the NR binding site was also mapped out. These activators are powerful chemical probes for the elucidation of cellular regulations and biological functions of SIRT5. The knowledge gained in this study can be used to guide the design and synthesis of more potent, isotype-selective SIRT5 activators and to develop them into therapeutics for metabolic disorders and age-related diseases.
Dual Room-Temperature Fluorescent and Phosphorescent Emission in 8-Quinolinolate Osmium(II) Carbonyl Complexes:  Rationalization and Generalization of Intersystem Crossing Dynamics (2005)

A new series of quinolinolate osmium carbonyl complexes were synthesized and characterized by spectroscopic methods. Single-crystal X-ray diffraction studies indicate that these complexes consist of an octahedral ligand arrangement with one chelating quinolinolate, one tfa or halide ligand, and three mutually orthogonal terminal CO ligands. Variation of the substituents on quinolinolate ligands imposes obvious electronic or structural effects, while changing the tfa ligand to an electron-donating iodide slightly increases the charge density on the central osmium atom. These Os(II) complexes show salient dual emissions consisting of fluorescence and phosphorescence, the spectral properties and relaxation dynamics of which have been studied comprehensively. The results, in combination with the theoretical approaches, lead us to propose that the emission mainly originates from the quinolinolate pi pi* state. Both experimental and theoretical approaches generalize various types of intersystem crossing versus those of the tris(quinolinolate) iridium Ir(Q)3, and their relative efficiencies were accessed on the basis of the associated frontier orbital configurations. Our results suggest that [1d(pi)pi* absolute value(H(so))3 pi pi*] (or [3d(pi)pi* absolute value(H(so))1 pi pi*]) in combination with a smaller deltaE(S1-T1) gap (i.e., increasing the MLCT (d(pi)pi*) character) is the main driving force to induce the ultrafast S1 --> T1 intersystem crossing in the third-row transition metal complexes, giving the strong phosphorescent emission.
A C/V segmentation algorithm for Mandarin speech signal based on wavelet transforms (1999)

This paper proposes a new consonant/vowel (C/V) segmentation algorithm for Mandarin speech signal. Since the Mandarin phoneme structure is a combination of a consonant (may be null) followed by a vowel, the C/V segmentation is an important part in the Mandarin speech recognition system. Based on the wavelet transform, the proposed method can directly search for the C/V segmentation point by using a product function and energy profile. The product function is generated from the appropriate wavelet and scaling coefficients of the input speech signal, and it can be applied to indicate the C/V segmentation point. With this product function and the additional verification of the energy profile, the C/V segmentation can be accurately pointed out with a low computation complexity. Experiments are provided that demonstrate the superior performance of the proposed algorithm. An overall accuracy rate of 97.2% is achieved. This algorithm is suitable for Mandarin speech recognition task.
Comparison of two commercial brands of microcrystalline cellulose for extrusion-spheronization (1997)

Two commercial brands of microcrystalline cellulose, the widely used Avicel PH-101 and the newly available Pharmacel 101, were compared for aqueous extrusion-spheronization of a model mix with lactose. Based on the results of multi-level experiments employing pellet size analysis by sieving and sphericity determination by image analysis, Avicel was shown to be less adversely affected by variation in added water or speed of spheronization. Physicochemical testing of powder samples from both brands was carried out using laser particle sized analysis, density determinations, differential scanning calorimetry and X-ray diffraction studies. The results indicated that the improved ease of processing with Avicel may be related to its smaller particle size with less aggregates, improved flow, lower depolymerization temperature range and absence of traces of cellulose II in its cellulose I content.
Therapeutic vaccination against HIV (2004)

The challenge for an immunotherapeutic vaccine is to increase antiviral responses in an increasingly immunocompromised host and to provide immunity to epitopes that have been neglected by the infected host. Therapeutic vaccination with structural and regulatory genes and proteins of HIV are reviewed. The most promising clinical results consist of short-term improvement in survival without antiretroviral therapy. Together with antiviral therapy, it is reported that immunization has provided a prolonged time to virological failure. It is clear, however, that additional help will be needed from adjuvants and/or modulators that activate natural killer and T-cells, or other immune molecules. Vaccine therapy should start early, while adequate reservoirs of appropriate T-helper and memory cells are available and still inducible.
Street-Scale Modeling of Storm Surge Inundation along the New Jersey Hudson River Waterfront (2015)

Abstract A new, high-resolution, hydrodynamic model that encompasses the urban coastal waters of New Jersey along the Hudson River Waterfront opposite New York City, New York, has been developed and validated for simulating inundation during Hurricane Sandy. A 3.1-m-resolution square model grid combined with a high-resolution lidar elevation dataset permits a street-by-street focus to inundation modeling. The waterfront inundation model is a triple-nested Stevens Institute Estuarine and Coastal Ocean Hydrodynamic Model (sECOM) application; sECOM is a successor model to the Princeton Ocean Model family of models. Robust flooding and drying of land in the model physics provides for the dynamic prediction of flood elevations and velocities across land features during inundation events. The inundation model was forced by water levels from the extensively validated New York Harbor Observing and Prediction System (NYHOPS) hindcast of that hurricane. Validation against 56 watermarks and 16 edgemarks provided via the USGS and through an extensive crowdsourcing effort consisting of photographs, videos, and personal stories shows that the model is capable of computing overland water elevations quite accurately throughout the entire surge event. The correlation coefficient ( R 2 ) between the watermark observations and the model results is 0.92. The standard deviation of the residual error is 0.07 m. Comparisons to the 16 flood edgemarks suggest that the model was able to reproduce flood extent to within 20 m. Because the model was able to capture the spatial and temporal variation of water levels in the region observed during Hurricane Sandy, it was used to identify the flood pathways and suggest where flood-preventing interventions could be built.
Blockchains as security-enabler for industrial IoT-applications (2017)

Purpose This paper aims to describe a method for Internet-of-Things-devices to achieve industrial grade reliability for information transfer from wireless sensor systems to production systems using blockchain technologies. Design/methodology/approach An increased security and reliability of submitted data within the sensor network could be achieved on an application level. Therefore, a lightweight, high-level communication protocol based on blockchain principles was designed. Findings Blockchain mechanisms can secure the wireless communication of Internet-of-Things-devices in a lightweight and scalable manner. Originality/value The innovation of this research is the successful application of general blockchain mechanisms to increase security of a wireless sensor system without binding to a dedicated blockchain technology.
Cross-species analyses implicate Lipin 1 involvement in human glucose metabolism (2005)

Recent studies in the mouse have demonstrated that variations in lipin expression levels in adipose tissue have marked effects on adipose tissue mass and insulin sensitivity. In the mouse, lipin deficiency prevents normal adipose tissue development, resulting in lipodystrophy and insulin resistance, whereas excess lipin levels promote fat accumulation and insulin sensitivity. Here, we investigated the effects of genetic variation in lipin levels on glucose homeostasis across species by analyzing lipin transcript levels in human and mouse adipose tissues. A strong negative correlation was observed between lipin mRNA levels and fasting glucose and insulin levels, as well as an indicator of insulin resistance (HOMA-IR), in both mice and humans. We subsequently analyzed the allelic diversity of the LPIN1 gene in dyslipidemic Finnish families, as well as in a case-control sample of obese (n = 477) and lean (n = 821) individuals. Alleles were defined by genotyping seven single nucleotide polymorphisms (SNPs) of the critical DNA region over the LPIN1 gene. Intragenic SNPs and corresponding allelic haplotypes exhibited associations with serum insulin levels and body mass index (P = 0.002-0.04). Both the expression levels in adipose tissue across species and genetic data in human study samples highlight the importance of lipin in glucose homeostasis and imply that allelic variants of this gene have significance in human metabolic traits.
Genetic differentiation and host preference reveal non‐exclusive host races in the generalist parasitic weed Phelipanche ramosa (2019)

Summary We developed 20 microsatellite markers to genotype over 100 populations of the parasitic weed Phelipanche ramosa, which covers a wide host crop and geographic range. A representative core collection of 15 populations was also used in cross‐infestation assays to study host preference during germination, attachment and shoot formation. We observed low genetic differentiation within most of the populations, but high genetic differentiation between populations partitioned into 3 genetic groups with different host preferences and geographic distributions. Genetic group 1 is detected exclusively in western France and on various host crops, notably winter oilseed rape ( WOSR ) and not hemp. Cross‐infection assays confirmed its incompatibility with hemp and showed its preference for WOSR and tobacco in terms of germination and attachment success. The group 2 populations share a large geographic distribution in France and Europe, low germination success with WOSR and high germination success, attachment success and shoot formation with hemp, tobacco or tomato. The subclades 2a and 2b include most of the French populations in hemp crops in eastern France and in tobacco fields in several European countries respectively. The genetic analyses revealed the potential of the three groups to increase their geographic range in the future. Intermediate genetic groups showed higher intrapopulation diversity and represent potential stocks for new host race emergence. Those findings argue in favour of the existence of host races in P. ramosa and should be considered for appropriate management strategies, notably in breeding programmes for resistance against this parasitic weed.
Commissioning status of the Virgo interferometer (2010)

We present a method to search for transient gravitational waves using a network of detectors with different spectral and directional sensitivities: the interferometer Virgo and the bar detector AURIGA. The data analysis method is based on the measurements of the correlated energy in the network by means of a weighted cross-correlation. To limit the computational load, this coherent analysis step is performed around time–frequency coincident triggers selected by an excess power event trigger generator tuned at low thresholds. The final selection of gravitational wave candidates is performed by a combined cut on the correlated energy and on the significance as measured by the event trigger generator. The method has been tested on one day of data of AURIGA and Virgo during September 2005. The outcomes are compared to the results of a stand-alone time–frequency coincidence search. We discuss the advantages and the limits of this approach, in view of a possible future joint search between AURIGA and one interferometric detector.
Power-Speed Trade-Offs in Design of Scaled FET Circuits Using C/I DS Methodology (2020)

An analytical approach to evaluate performance of analog integrated circuits and make a comparative study in different technology nodes is presented. To provide closed-form solutions, this article proposes using C = C/IDS as an independent design variable, where C refers to any physical or parasitic capacitance associated with a Field-Effect Transistor (FET) biased at I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">DS</sub> . The proposed C-based methodology is used to study speed versus power trade-offs in both continuous-time (CT) and discrete-time (DT) circuits. Predictive Technology Models (PTMs) have been used to study performance of both MOSFET and FinFET (i.e. FET) devices in different technology nodes. This analysis shows that FinFET transistors exhibit a wider medium-inversion region compared to MOSFET devices, making them more convenient for high-speed and low-power designs. Additionally, this study proves that a lower sub-threshold slope factor results in an improved energy-efficiency of analog circuits.
The impact of extended lymph node dissection versus neoadjuvant therapy with limited lymph node dissection on biochemical recurrence in high-risk prostate cancer patients treated with radical prostatectomy: A multi-institutional analysis. (2017)

e543 Background: The optimal treatment for high-risk prostate cancer (Pca) remains to be established. We previously reported favorable biochemical recurrence-free survival (BRFS) in high-risk Pca patients treated with neoadjuvant therapy comprising a luteinizing-hormone-releasing hormone (LHRH) agonist plus low-dose estramustine phosphate (EMP) (LHRH+EMP) followed by radical prostatectomy (RP). The aim of this study was to assess whether neoadjuvant LHRH+EMP confers an oncological benefit for high-risk Pca compared to extended lymph node dissection (e-PLND). Methods: The Michinoku Urological Cancer Study Group database contained the data of 2403 consecutive Pca patients treated with RP at 4 institutes between March 2000 and December 2014. In the e-PLND group, we identified 238 high-risk Pca patients who underwent RP and e-PLND, with lymphatic tissue removal around the obturator and the external iliac regions, and hypogastric lymph node dissection. The neoadjuvant therapy with limited PLND (l-PLND) group included 280 high-risk Pca patients who underwent RP and removal of the obturator node chain between September 2005 and June 2014 at Hirosaki University. The neoadjuvant LHRH+EMP therapy included the administration of 280 mg/day of LHRH and EMP for 6 months before RP. The outcome measure was BRFS. Results: The 5-year BRFS rates for the neoadjuvant therapy with l-PLND group and e-PLND group were 84.9% and 54.7%, respectively ( P &lt; 0.0001). The operative time was significantly longer in the e-PLND group compared to that of the neoadjuvant therapy with l-PLND group. Grade 3/4 surgery-related complications were not identified in both groups. Conclusions: Although the present study was not randomized, neoadjuvant LHRH+EMP therapy followed by RP might reduce the risk of biochemical recurrence.
Dataset Culling: Towards Efficient Training Of Distillation-Based Domain Specific Models (2019)

Real-time CNN-based object detection models for applications like surveillance can achieve high accuracy but are computationally expensive. Recent works have shown 10 to 100x reduction in computation cost for inference by using domain-specific networks. However, prior works have focused on inference only. If the domain model requires frequent retraining, training costs can pose a significant bottleneck. To address this, we propose Dataset Culling: a pipeline to reduce the size of the dataset for training, based on the prediction difficulty. Images that are easy to classify are filtered out since they contribute little to improving the accuracy. The difficulty is measured using our proposed confidence loss metric with little computational overhead. Dataset Culling is extended to optimize the image resolution to further improve training and inference costs. We develop fixed-angle, long-duration video datasets across several domains, and we show that the dataset size can be culled by a factor of 300x to reduce the total training time by 47x with no accuracy loss or even with slight improvement. Codes are available: https://github.com/kentaroy47/DatasetCulling
2378Blunted stress myocardial oxygenation and not myocardial perfusion reserve is associated with arrhythmic risk in hypertrophic cardiomyopathy (2019)

Abstract Background In hypertrophic cardiomyopathy (HCM), myocardial ischaemia is believed to play a role in fatal life-threatening ventricular arrhythmias and caused by microvascular dysfunction manifesting as impaired myocardial perfusion. However, previous studies suggest that myocardial oxygenation during vasodilator stress may also be blunted when perfusion is normal, due to increased metabolic demands conferred by energy-costly sarcomeric mutations, left ventricular hypertrophy and outflow obstruction. Whether or not impaired myocardial perfusion reserve or blunted stress oxygenation on cardiac magnetic resonance (CMR) predict the risk of ventricular arrhythmia in HCM is unknown. Purpose We sought to investigate if impaired myocardial perfusion reserve or stress oxygenation is associated with an increased risk of ventricular arrhythmia in HCM. Methods 103 genotyped HCM patients (mean age 47±15 years) and 32 age- and sex-matched healthy controls underwent adenosine stress blood oxygen level dependent (BOLD) imaging, first pass perfusion and late gadolinium imaging (LGE) on CMR to assess stress oxygenation (BOLD ΔSI), myocardial perfusion reserve index (MPRI), and fibrosis respectively. All HCM patients were monitored for ventricular tachycardia (≥3 beats, ≥120 beats per minute) on a 24-hour Holter. Results As expected, MPRI was significantly reduced in HCM (1.5±0.4 vs 2.0±0.3, p&lt;0.0001) compared to controls. Stress oxygenation response was blunted in HCM versus controls (9.1±4.1% vs 17.0±1.6%, p&lt;0.0001, Figure 1B). Twenty-six (25%) patients developed ventricular tachycardia on Holter monitoring. On univariate analysis, only stress oxygenation and not MPRI associated with ventricular tachycardia. The prevalence of ventricular tachycardia in HCM increased with decreasing quartiles of stress oxygenation (Figure 1D). HCM patients in the lowest quartile of oxygenation (BOLD ΔSI &lt;6.5%) were at a three-fold risk of ventricular tachycardia (OR 3.04, 95% confidence interval 1.02–9.05, p=0.04) on multivariable analysis (after adjusting for sudden cardiac death risk factors and LGE mass) compared to other patients. Sarcomeric mutation status was an independent determinant of stress oxygenation on multivariable analysis. Stress oxygenation was impaired in phenotype-negative sarcomeric mutation carriers (Sarc+P-, n=16) despite normal perfusion (Figure 1C, E). Sarcomeric HCM (Sarc+HCM) had more severe impairment in stress oxygenation than genotype negative HCM (G-HCM) and controls (Figure 1E). Figure 1 Conclusion In HCM, blunted stress-induced oxygenation is associated with an increased risk of ventricular arrhythmia and may represent a novel biomarker of arrhythmic risk. Sarcomeric mutation status is an important determinant of stress oxygenation response. Acknowledgement/Funding National Institute for Health Research Oxford Biomedical Centre and British Heart Foundation.
Anticholinergic Burden Assessed Using General Practice Electronic Records (2013)

ABSTRACT Aim To determine the anticholinergic burden (ACB) of an Australian primary care population. Method A cross‐sectional study was undertaken of medication data from 11 general practices. Participants were active patients aged 65 years and over seen at least 3 times in the last 2 years (n = 4853). The ACB score was calculated based on a UK peer‐reviewed scoring system (Fox) and a modified scale (Fox‐plus) that included medications not present in the Fox scale. The main outcome measure was total ACB from prescribed medications. Results A Fox ACB score ≥ 4 is associated with increased risk of morbidity and mortality, 249 (9%) females, 130 (6%) males and 379 (8%) overall fell in this category. Applying the Fox‐plus ACB scale, 983 (36%) females, 630 (30%) males and 1613 (33%) overall fell in this category. Conclusion A large proportion of the elderly population may have cognitive impairment because of their therapy. Alternative medications or strategies are needed to maintain therapeutic benefits with a low ACB.