2,227 research outputs found

    Specific recognition of a multiply phosphorylated motif in the DNA repair scaffold XRCC1 by the FHA domain of human PNK.

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    Short-patch repair of DNA single-strand breaks and gaps (SSB) is coordinated by XRCC1, a scaffold protein that recruits the DNA polymerase and DNA ligase required for filling and sealing the damaged strand. XRCC1 can also recruit end-processing enzymes, such as PNK (polynucleotide kinase 3'-phosphatase), Aprataxin and APLF (aprataxin/PNK-like factor), which ensure the availability of a free 3'-hydroxyl on one side of the gap, and a 5'-phosphate group on the other, for the polymerase and ligase reactions respectively. PNK binds to a phosphorylated segment of XRCC1 (between its two C-terminal BRCT domains) via its Forkhead-associated (FHA) domain. We show here, contrary to previous studies, that the FHA domain of PNK binds specifically, and with high affinity to a multiply phosphorylated motif in XRCC1 containing a pSer-pThr dipeptide, and forms a 2:1 PNK:XRCC1 complex. The high-resolution crystal structure of a PNK-FHA-XRCC1 phosphopeptide complex reveals the basis for this unusual bis-phosphopeptide recognition, which is probably a common feature of the known XRCC1-associating end-processing enzymes

    Effects of exercise modalities on arterial stiffness and wave reflection: a systematic review and meta-analysis of randomized controlled trials

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    Background and Objectives: Physical activity is associated with lower cardiovascular and all-cause mortality. However, the effects of different exercise modalities on arterial stiffness are currently unclear. Our objectives were to investigate the effects of exercise modalities (aerobic, resistance or combined) on pulse wave velocity (PWV) and augmentation index (AIx), and to determine whether the effects on these indices differed according to the participants' or exercise characteristics. Methods: We searched the Medline, Embase and Cochrane Library databases from inception until April 2014 for randomized controlled trials lasting ≥4 weeks investigating the effects of exercise modalities on PWV and AIx in adults aged ≥18 years. Results: Forty-two studies (1627 participants) were included in this analysis. Aerobic exercise improved both PWV (WMD: −0.63 m/s, 95% CI: −0.90, −0.35) and AIx (WMD:−2.63%, 95% CI: −5.25 to −0.02) significantly. Aerobic exercise training showed significantly greater reduction in brachial-ankle (WMD: −1.01 m/s, 95% CI: −1.57, −0.44) than in carotid-femoral (WMD: -0.39 m/s, 95% CI: −0.52, −0.27) PWV. Higher aerobic exercise intensity was associated with larger reductions in AIx (β: −1.55%, CI −3.09, 0.0001). In addition, aerobic exercise had a significantly larger effect in reducing PWV (WMD:−1.0 m/s, 95% CI: −1.43, −0.57) in participants with stiffer arteries (PWV ≥8 m/s). Resistance exercise had no effect on PWV and AIx. There was no significant effect of combined exercise on PWV and AIx. Conclusions: We conclude that aerobic exercise improved arterial stiffness significantly and that the effect was enhanced with higher aerobic exercise intensity and in participants with greater arterial stiffness at baseline. Trial Registration PROSPERO: Database registration: CRD42014009744,

    On Multilingual Training of Neural Dependency Parsers

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    We show that a recently proposed neural dependency parser can be improved by joint training on multiple languages from the same family. The parser is implemented as a deep neural network whose only input is orthographic representations of words. In order to successfully parse, the network has to discover how linguistically relevant concepts can be inferred from word spellings. We analyze the representations of characters and words that are learned by the network to establish which properties of languages were accounted for. In particular we show that the parser has approximately learned to associate Latin characters with their Cyrillic counterparts and that it can group Polish and Russian words that have a similar grammatical function. Finally, we evaluate the parser on selected languages from the Universal Dependencies dataset and show that it is competitive with other recently proposed state-of-the art methods, while having a simple structure.Comment: preprint accepted into the TSD201

    Artificial Intelligence and customers service in banking: the bank of the future Monzo

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    Purpose: Our research studies the impact of artificial intelligence (AI) banking service innovation on Y-generation customers’ lifestyle. Recently financial technology (FinTech) applications have attracted large demand for mobile banking users targeting youth generation by using smartphone apps banking services. This research focuses on the banking service innovation using AI and its impact mobile banking customers, young generation customers in particular. The FinTech applications developers monitored all their customer expenses using these financial wallets to monitor their life-style and daily expenses data. The financial service innovation makes life easier and convenient for customers, but it helps several companies to monitor the youth generation interest and data. These data could have been used in an unethical way without their awareness and consents. There is an urgent requirement to understand this phenomenon and improve more regulations to improve the security and ethical standard for such data and regulate these financial technology wallets. The study considered artificial intelligence security, risk and ethics as a moderator for these relationships. Monzo is one of the famous financial technology platforms which announce that 55K users apply for their wallet in weekly bases, moreover, they are targeting the youth generation. It was founded since 2015 which power progressing business within 2018 and 2019. This case is one of the main popular financial technology platforms in the United Kingdom which this study adopted. More than 1 million new customers join Monzo last year, and the customer deposits increased by 390miion pound with the last year 2018/2019 which reflect the demand from customer side to use such technology. Design/methodology/approach: A research framework was developed based upon thorough literature review on artificial intelligence and banking service innovations. The Data of this study will be targeting on over than 8000 youth users in the United Kingdom using social media platforms such as Facebook, Instagram and Snapchat. Online questionnaires targeted to be active to discover how artificial intelligence financial applications leads to service addiction through social influence and service innovation. The moderating role AI risks and security and AI ethics will also be analysed in this study. Findings: The results will reveal how AI platforms controlled youth generation life-style by attracting them to use such financial wallet. The results will reflect the impact of AI within the coming years on government regulations to avoid any risk and to build security for customer data through having data protection. The results will also be addressing the role of the government and society to control these companies’ data by having an ethical agreement for data protection. Practical implications: The study aims to help the regulators to build rules for avoiding any risk and to have data protection for Y – generation lifestyle expenses. Moreover, to build a rule for Financial Technology companies to protect their data and regulate their service. It will reflect how the government bodies need to control the artificial intelligence of the innovated banking service big data which could use unethically regarding customer lifestyle and personal information’s. Originality/value: This paper designs a conceptual framework to determine how financial technology applications using artificial intelligence techniques could impact Y-generation life-style data. This paper is one of a few studies, which focus on the importance of Fintech AI platforms toward the business environment. At the same time, how AI ethics rules need to be set up by governments to avoid any risk and build data protection for youth generation users. This is an example of a case study that attempts to target Y-generation on daily bases to attract them using such intelligence platform on their daily bases. Keywords: Fin-tech, Artificial intelligence, service addiction, social influence, AI ethics, AI risk and security, Monzo Paper type: Research pape

    Pilonidal Sinus Management Using 980 nm Diode Laser

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    Background: Pilonidal sinus is a chronic, debilitating disease of the natal cleft. It mainly involves the sacrococcygeal region and the presentation varies from asymptomatic pits to painful abscesses or sinuses. Treatment options vary from observation to wide excision. Unfortunately, surgical treatment may result in recurrence. Many conservative methods had being described for treatment of pilonidal sinus, photocoagulation using laser is one of them.The aim of study: To assess the efficacy of laser (diode) as a therapy to the pilonidal sinus.Design: A cohort of five patients with a provisional diagnosis of  pilonidal sinus (unbranched) were treated by photocoagulation of sinus tract by diode laser 980 nm, between 17 and 25 year old (20.6±2.58), were diagnosed clinically and by sinogram to know the exact length of the tract and to exclude branching tract. The average length of the tracts were (5 cm) ranging (3-7) cm. Only one patient had recurrent sinus after surgical excision.Result: The mean operative time was (10.10) min. (range of 6.10-14.10 min.). All patient were seen the day after the procedure and then weekly, only one patient had pus discharge at day nine and was treated with ciprofloxacin and metronidazole for ten days and tract closed after 21 days of the procedure. The average time for closure was (10.4) day ranging (6-21).conclusion: Diode laser as a surgical tools in the treatment of pilonidal sinus offers the following benefits: Reducing hospital stay, minimizing tissue assault by avoiding unduly extensive procedures with the attendant complications, early resumption of work by the patient and preventing recurrence of the disease. Keywords: pilonidal, diode 980nm, diode lase

    Nonperturbative corrections to B -> X_s l^+ l^- with phase space restrictions

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    We study nonperturbative corrections up to O(1/m_b^3) in the inclusive rare B decay B -> X_s l^+ l^- by performing an operator product expansion. The values of the matrix elements entering at this order are unknown and introduce uncertainties into physical quantities. Imposing a phase space cut to eliminate the ccˉc \bar{c} resonances we find that the O(1/m_b^3) corrections introduce an O(10%) uncertainty in the measured rate. We also find that the contributions arising at O(1/m_b^3) are comparable to the ones arising at O(1/m_b^2) over the entire region of phase space.Comment: 7 pages, 2 figures, revte
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