Increased Neutrophil Elastase and Proteinase 3 and Augmented NETosis Are Closely Associated With β-Cell Autoimmunity in Patients With Type 1 Diabetes

Type 1 diabetes (T1D) is an autoimmune disease resulting from the self-destruction of insulin-producing β-cells. Reduced neutrophil counts have been observed in patients with T1D. However, the pathological roles of neutrophils in the development of T1D remain unknown. Here we show that circulating protein levels and enzymatic activities of neutrophil elastase (NE) and proteinase 3 (PR3), both of which are neutrophil serine proteases stored in neutrophil primary granules, were markedly elevated in patients with T1D, especially those with disease duration of less than 1 year. Furthermore, circulating NE and PR3 levels increased progressively with the increase of the positive numbers and titers of the autoantibodies against β-cell antigens. An obvious elevation of NE and PR3 was detected even in those autoantibody-negative patients. Increased NE and PR3 in T1D patients are closely associated with elevated formation of neutrophil extracellular traps. By contrast, the circulating levels of α1-antitrypsin, an endogenous inhibitor of neutrophil serine proteases, are decreased in T1D patients. These findings support an early role of neutrophil activation and augmented neutrophil serine proteases activities in the pathogenesis of β-cell autoimmunity and also suggest that circulating NE and PR3 may serve as sensitive biomarkers for the diagnosis of T1D.postprin

Bi-local Construction of Sp(2N)/dS Higher Spin Correspondence

We derive a collective field theory of the singlet sector of the Sp(2N) sigma model. Interestingly the hamiltonian for the bilocal collective field is the same as that of the O(N) model. However, the large-N saddle points of the two models differ by a sign. This leads to a fluctuation hamiltonian with a negative quadratic term and alternating signs in the nonlinear terms which correctly reproduces the correlation functions of the singlet sector. Assuming the validity of the connection between O(N) collective fields and higher spin fields in AdS, we argue that a natural interpretation of this theory is by a double analytic continuation, leading to the dS/CFT correspondence proposed by Anninos, Hartman and Strominger. The bi-local construction gives a map into the bulk of de Sitter space-time. Its geometric pseudospin-representation provides a framework for quantization and definition of the Hilbert space. We argue that this is consistent with finite N grassmanian constraints, establishing the bi-local representation as a nonperturbative framework for quantization of Higher Spin Gravity in de Sitter space.Comment: 1 figur

Silicon Atomic Quantum Dots Enable Beyond-CMOS Electronics

We review our recent efforts in building atom-scale quantum-dot cellular automata circuits on a silicon surface. Our building block consists of silicon dangling bond on a H-Si(001) surface, which has been shown to act as a quantum dot. First the fabrication, experimental imaging, and charging character of the dangling bond are discussed. We then show how precise assemblies of such dots can be created to form artificial molecules. Such complex structures can be used as systems with custom optical properties, circuit elements for quantum-dot cellular automata, and quantum computing. Considerations on macro-to-atom connections are discussed.Comment: 28 pages, 19 figure

A web-based appointment system to reduce waiting for outpatients: A retrospective study

<p>Abstract</p> <p>Background</p> <p>Long waiting times for registration to see a doctor is problematic in China, especially in tertiary hospitals. To address this issue, a web-based appointment system was developed for the Xijing hospital. The aim of this study was to investigate the efficacy of the web-based appointment system in the registration service for outpatients.</p> <p>Methods</p> <p>Data from the web-based appointment system in Xijing hospital from January to December 2010 were collected using a stratified random sampling method, from which participants were randomly selected for a telephone interview asking for detailed information on using the system. Patients who registered through registration windows were randomly selected as a comparison group, and completed a questionnaire on-site.</p> <p>Results</p> <p>A total of 5641 patients using the online booking service were available for data analysis. Of them, 500 were randomly selected, and 369 (73.8%) completed a telephone interview. Of the 500 patients using the usual queuing method who were randomly selected for inclusion in the study, responses were obtained from 463, a response rate of 92.6%. Between the two registration methods, there were significant differences in age, degree of satisfaction, and total waiting time (<it>P </it>< 0.001). However, gender, urban residence, and valid waiting time showed no significant differences (<it>P </it>> 0.05). Being ignorant of online registration, not trusting the internet, and a lack of ability to use a computer were three main reasons given for not using the web-based appointment system. The overall proportion of non-attendance was 14.4% for those using the web-based appointment system, and the non-attendance rate was significantly different among different hospital departments, day of the week, and time of the day (<it>P </it>< 0.001).</p> <p>Conclusion</p> <p>Compared to the usual queuing method, the web-based appointment system could significantly increase patient's satisfaction with registration and reduce total waiting time effectively. However, further improvements are needed for broad use of the system.</p

Sleep quality in middle-aged and elderly Chinese: distribution, associated factors and associations with cardio-metabolic risk factors

Background Poor sleep quality has been associated with increased risk of heart disease, diabetes and mortality. However, limited information exists on the distribution and determinants of sleep quality and its associations with cardio-metabolic risk factors in Chinese populations. We aimed to evaluate this in the current study. Methods A cross-sectional survey conducted in 2005 of 1,458 men and 1,831 women aged 50–70 years from urban and rural areas of Beijing and Shanghai. Using a questionnaire, sleep quality was measured in levels of well, common and poor. Comprehensive measures of socio-demographical and health factors and biomarkers of cardio-metabolic disease were recorded. These were evaluated in association with sleep quality using logistic regression models. Results Half of the population reported good sleep quality. After adjusting for potential confounders, women and Beijing residents had almost half the probability to report good sleep quality. Good physical and mental health (good levels of self-rated health (OR 2.48; 95%CI 2.08 to 2.96) and no depression (OR 4.05; 95%CI 3.12 to 5.26)) related to an increased chance of reporting good sleep quality, whereas short sleep duration (<7 hrs OR 0.10; 95%CI 0.07 to 0.14)) decreased it substantially. There were significant associations between levels of sleep quality and concentrations of plasma insulin, total and LDL cholesterol, and index of insulin resistance. Conclusion Levels of good sleep quality in middle-age and elderly Chinese were low. Gender, geographical location, self-rated health, depression and sleep quantity were major factors associated with sleep quality. Prospective studies are required to distil the factors that determine sleep quality and the effects that sleep patterns exert on cardio-metabolic health

Modulating signaling networks by CRISPR/Cas9-mediated transposable element insertion

In a recent past, transposable elements (TEs) were referred to as selfish genetic components only capable of copying themselves with the aim of increasing the odds of being inherited. Nonetheless, TEs have been initially proposed as positive control elements acting in synergy with the host. Nowadays, it is well known that TE movement into host genome comprises an important evolutionary mechanism capable of increasing the adaptive fitness. As insights into TE functioning are increasing day to day, the manipulation of transposition has raised an interesting possibility of setting the host functions, although the lack of appropriate genome engineering tools has unpaved it. Fortunately, the emergence of genome editing technologies based on programmable nucleases, and especially the arrival of a multipurpose RNA-guided Cas9 endonuclease system, has made it possible to reconsider this challenge. For such purpose, a particular type of transposons referred to as miniature inverted-repeat transposable elements (MITEs) has shown a series of interesting characteristics for designing functional drivers. Here, recent insights into MITE elements and versatile RNA-guided CRISPR/Cas9 genome engineering system are given to understand how to deploy the potential of TEs for control of the host transcriptional activity.Fil: Vaschetto, Luis Maria Benjamin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Diversidad y Ecología Animal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto de Diversidad y Ecología Animal; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Diversidad Animal I; Argentin

Wavelet packets based denoising method for measurement domain repeat-time multipath filtering in GPS static high-precision positioning

Repeatable satellite orbits can be used for multipath mitigation in GPS-based deformation monitoring and other high-precision GPS applications that involve continuous observation with static antennas. Multipath signals at a static station repeat when the GPS constellation repeats given the same site environment. Repeat-time multipath filtering techniques need noise reduction methods to remove the white noise in carrier phase measurement residuals in order to retrieve the carrier phase multipath corrections for the next day. We propose a generic and robust three-level wavelet packets based denoising method for repeat-time-based carrier phase multipath filtering in relative positioning; the method does not need tuning to work with different data sets. The proposed denoising method is tested rigorously and compared with two other denoising methods. Three rooftop data sets collected at the University of Nottingham Ningbo China and two data sets collected at three Southern California Integrated GPS Network high-rate stations are used in the performance assessment. Test results of the wavelet packets denoising method are compared with the results of the resistor–capacitor (RC) low-pass filter and the single-level discrete wavelet transform (DWT) denoising method. Multipath mitigation efficiency in carrier phase measurement domain is shown by spectrum analysis of two selected satellites in two data sets. The positioning performance of the repeat-time-based multipath filtering techniques is assessed. The results show that the performance of the three noise reduction techniques is about 1–46 % improvement on positioning accuracy when compared with no multipath filtering. The statistical results show that the wavelet packets based denoising method is always better than the RC filter by 2–4 %, and better than the DWT method by 6–15 %. These results suggest that the proposed wavelet packets based denoising method is better than both the DWT method and the relatively simple RC low-pass filter for noise reduction in multipath filtering. However, the wavelet packets based denoising method is not significantly better than the RC filter

Novel AroA from Pseudomonas putida Confers Tobacco Plant with High Tolerance to Glyphosate

Glyphosate is a non-selective broad-spectrum herbicide that inhibits 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS, also designated as AroA), a key enzyme in the aromatic amino acid biosynthesis pathway in microorganisms and plants. Previously, we reported that a novel AroA (PpAroA1) from Pseudomonas putida had high tolerance to glyphosate, with little homology to class I or class II glyphosate-tolerant AroA. In this study, the coding sequence of PpAroA1 was optimized for tobacco. For maturation of the enzyme in chloroplast, a chloroplast transit peptide coding sequence was fused in frame with the optimized aroA gene (PparoA1optimized) at the 5′ end. The PparoA1optimized gene was introduced into the tobacco (Nicotiana tabacum L. cv. W38) genome via Agrobacterium-mediated transformation. The transformed explants were first screened in shoot induction medium containing kanamycin. Then glyphosate tolerance was assayed in putative transgenic plants and its T1 progeny. Our results show that the PpAroA1 from Pseudomonas putida can efficiently confer tobacco plants with high glyphosate tolerance. Transgenic tobacco overexpressing the PparoA1optimized gene exhibit high tolerance to glyphosate, which suggest that the novel PpAroA1 is a new and good candidate applied in transgenic crops with glyphosate tolerance in future

DNA-PK Is Targeted by Multiple Vaccinia Virus Proteins to Inhibit DNA Sensing

Virus infection is sensed by pattern recognition receptors (PRRs) detecting virus nucleic acids and initiating an innate immune response. DNA-dependent protein kinase (DNA-PK) is a PRR that binds cytosolic DNA and is antagonized by vaccinia virus (VACV) protein C16. Here, VACV protein C4 is also shown to antagonize DNA-PK by binding to Ku and blocking Ku binding to DNA, leading to a reduced production of cytokines and chemokines in vivo and a diminished recruitment of inflammatory cells. C4 and C16 share redundancy in that a double deletion virus has reduced virulence not seen with single deletion viruses following intradermal infection. However, non-redundant functions exist because both single deletion viruses display attenuated virulence compared to wild-type VACV after intranasal infection. It is notable that VACV expresses two proteins to antagonize DNA-PK, but it is not known to target other DNA sensors, emphasizing the importance of this PRR in the response to infection in vivo