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Studies on rodents and nonhuman primates suggest that exposure to anesthetics, particularly in the young brain, is associated with neuronal apoptosis as well as hippocampal-dependent cognitive dysfunction. Disruption of the development of dentate gyrus may play an important role in anesthetics-induced neurotoxicity. However, the anesthetics triggered molecular events in the dentate gyrus of the developing brain are poorly understood. By integrating two independent data sets obtained from miRNA‑seq and mRNA-seq respectively, this study aims to profile the network of miRNA and potential target genes, as well as relevant events occurring in the dentate gyrus of isoflurane exposed 7-day-old mice. We found that a single four hours exposure to isoflurane yielded 1059 pairs of differently expressed miRNAs/target genes in the dentate gyrus. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis further indicates that dysregulated miRNAs/target genes have far‑reaching effects on the cellular pathophysiological events, such as cell apoptosis, axon development, and synaptic transmission. Our results would greatly broaden our functional understanding of the role of miRNA/target gene in the context of anesthetics-induced neurotoxicity.

We present a novel backside-illuminated single photon avalanche diode (SPAD) which is compatible with standard CMOS technology. The structure of SPAD is based on p-i-n junction which is the first time to be used to backsideilluminated structure, thus enabling a significantly low dark count rate (DCR). In order to get better photon detection efficiency (PDE) in near-infrared , we optimized the junction width and thickness of the device. The structure of SPAD is designed by the TCAD Devedit tool, and some important characteristic parameters are extracted by the Atlas tool. We calculate DCR and PDE using the extracted parameters. At 5 V excess bias voltage, the DCR of 0.81 Hz/μm2 is achieved at room temperature. The PDE at 5 V excess bias voltage is 20%. The fill factor is up to 53%. The DCR of the structure has reached the international advanced level.

Single photon avalanche diode (SPAD) in Geiger mode is a kind of detector which can detect extremely faint signal, and has been greatly developed in recent years due to the single photon sensitivity, time resolution on the order of picoseconds and high photon-detection efficiency. The device has been widely applied in time-resolved spectrum measurement, quantum imaging and quantum cryptography. The dark count rate (DCR) is one of the key parameters to judge the performance of the device. However, high DCR is a common problem in the world, especially for the device with large sensitive area. In recent years, the research of the device with low DCR is in-depth, and some remarkable achievements have been made, including the establishment of the physical simulation model and the optimization of structure. In this paper, based on the previous research results, we analyze the physical mechanism of the generation of DCR, including Shockley Read Hall (SRH), Trap-Assisted Tunneling (TAT), and Band to Band Tunneling (BTBT), and describe the method of physical model simulation using Technology Computer-Aided Design (TCAD) software. On the other hand, we have studied the structure of the device with low DCR and summarize their advantages, respectively. It is hoped that through in-depth research on the physical model and structure design theory, we can find a way to reduce the DCR of the device, so as to improve its performance.

Objective There has been no epidemiological survey of it in Tibet. We estimated the prevalence of rheumatoid arthritis in Luoma Town, Naqu City, Tibet Autonomous Region of China. Methods A population-based cross-sectional survey was conducted among 1458 residents of Luoma Town, Tibet Autonomous Region, aged ≥ 40 years. We used questionnaires in face-to-face interviews, anthropometric measurements and rheumatoid factor (RF), autoantibodies binding to citrullinated antigens (ACPA) and C-reactive protein (CRP) test. The definition of rheumatoid arthritis in this study was on the basis of new 2010 ACR/EULAR classification criteria. Results 782 participants completed all items of rheumatoid arthritis. The overall crude prevalence of rheumatoid arthritis was 4.86%. The prevalence was higher in women than in men (7.14% vs. 2.56%, P = 0.005). Tibetan had a higher age-standardized prevalence of rheumatoid arthritis 6.30% (95% confidence interval: 4.20% − 8.64%) compared with the other areas in China (range: 0.20% − 0.93%). Conclusion The prevalence of rheumatoid arthritis is relatively higher than other places in China.

DNA G-quadruplexes are not only attractive drug targets for cancer therapeutics, but also have important applications in supramolecular assembly. Here, we report a platinum(II)-based tripod (Pt-tripod) specifically binds the biological relevant hybrid-1 human telomeric G-quadruplex (Tel26), and strongly inhibits telomerase activity. Further investigations illustrate Pt-tripod induces the formation of monomeric and multimeric Pt-tripod‒Tel26 complex structures in solution. We solve the 1:1 and the unique dimeric 4:2 Pt-tripod–Tel26 complex structures by NMR. The structures indicate preferential binding of Pt-tripod to the 5ʹ-end of Tel26 at a low Pt-tripod/Tel26 ratio of 0–1.0. After adding more Pt-tripod, the Pt-tripod binds the 3ʹ-end of Tel26, unexpectedly inducing a unique dimeric 4:2 structure interlocked by an A:A non-canonical pair at the 3ʹ-end. Our structures provide a structural basis for understanding the dynamic binding of small molecules with G-quadruplex and DNA damage mechanisms, and insights into the recognition and assembly of higher-order G-quadruplexes., DNA G-quadruplexes occur in oncologically relevant regions, thus are interesting targets for cancer research and treatment. Here, the authors solved the 1:1 and 4:2 (ligand/DNA) NMR structures of human telomeric DNA in complex with platinum(II)-tripod ligand and show that the binding is dynamic.

Life-cycle assessment (LCA) was conducted to quantitatively assess the total environmental impacts of membrane bioreactor (MBR) and tertiary technologies treating wastewater in the fruit processing sector, allowing comparisons on the impacts of different treatment options, including impacts without on-site treatment. The system boundaries for all scenarios comprise raw materials extraction and processing, transportation, construction, operation and waste disposal. SimaPro 8.0.4.26 was used as the software tool, and two impact assessment methods (ReCiPe v1.11 and TRACI v2.1) were applied. Results showed that MBR combined with RO and UV contributed the least damage to the ecosystem, and minimized eutrophication impacts from the sewage when compared to the non-treatment scenario. Treating wastewater in municipal wastewater treatment plants (WWTP) would mitigate eutrophication effects, but it resulted in more environmental impacts from categories such as climate change and human health compared with implementing on-site treatment systems.

BACKGROUND Identifying high-grade features in patients with pancreatic mucinous neoplasms (MNs) is important for patient management. The reproducibility of MN cytology grading has been evaluated to a limited extent. In the current study, the authors evaluated interobserver variability in grading MNs and the identification of neoplastic mucin in endoscopic ultrasound-guided fine-needle aspiration specimens. METHODS A 54-case grading set was created from histologically confirmed MNs (44 MNs) and nonmucinous lesions with abundant gastrointestinal contamination (10 nonmucinous lesions). Six observers received a tutorial, reviewed prescreened slides, and recorded: 1) a diagnosis according to a 6-tiered system (TS) (nondiagnostic, atypical [ATP], mucinous cyst low grade [MCLG], mucinous cyst high grade, suspicious for adenocarcinoma, and positive for adenocarcinoma); 2) the cyst fluid carcinoembryonic antigen diagnosis (CEADX); and 3) the presence of neoplastic musin. Interobserver agreement (IOA) was evaluated by calculation of kappa coefficients (Kappa). Diagnostic accuracy was not evaluated. RESULTS The IOA was lowest for the 6-TS (Kappa, 0.13; P

BACKGROUND Touch preparations (TPs) can be performed for on-site adequacy assessment of core needle biopsies (CNBs). Although TPs can play a role in decreasing the number of nondiagnostic core biopsies, the impact of TPs on CNB has not been extensively evaluated. METHODS Computerized tomography–guided CNBs performed in a tertiary cancer center were retrospectively identified. On-site adequacy assessment was performed in all cases. The matching TPs and CNBs were evaluated for diagnostic accuracy of the TP. The relation between the site of biopsy and the cellularity of the CNB was also analyzed. RESULTS A total of 1100 CNB cases with associated TPs were identified over a 6-month period. Eighty-four cases (8%) showed marked differences in cellularity between CNB and TP, and 43 of these 84 cases (4.3%) showed the presence of diagnostic cells in either CNB or TP, but not in both. Lung was the biopsy site where CNB was most affected by loss of diagnostic cells. CONCLUSIONS TP and CNB findings must be integrated to prevent a misdiagnosis. Lung CNBs were more frequently affected by performing TPs. Cancer (Cancer Cytopathol) 2014;122:851–854. © 2014 American Cancer Society.

A novel state-space self-tuning control methodology for a nonlinear stochastic hybrid system with stochastic noise/disturbances is proposed in this paper. via the optimal linearization approach, an adjustable NARMAX-based noise model with estimated states can be constructed for the state-space self-tuning control in nonlinear continuous-time stochastic systems. Then, a corresponding adaptive digital control scheme is proposed for continuous-time multivariable nonlinear stochastic systems, which have unknown system parameters, measurement noise/external disturbances, and inaccessible system states. The proposed method enables the development of a digitally implementable advanced control algorithm for nonlinear stochastic hybrid systems.

In this paper, we propose a finite-time convergent interval type-2 fuzzy sliding-mode controller (FTC-1T2-FSMC) for trajectory control of a tri-wheel omni-directional mobile robot (ODMR) with system uncertainties and external disturbances. This control scheme combines the techniques of terminal attractor approach, type-2 fuzzy logic control, and sliding-mode control which can drive the error states to zero in finite time. All the simulation results demonstrate the effectiveness of the proposed control method.

BACKGROUND Rare studies have reported the application of multiple ancillary tests to the diagnosis of lymphoproliferative disorder in serous effusions. In the current study, the authors evaluated the effectiveness of using an algorithm for the triage of serous effusions and the contribution of ancillary studies to achieve a specific subtype of lymphoproliferative disorder. METHODS Serous effusion samples that had a final diagnosis of lymphoproliferative disorder or suspicious for lymphoma were selected from cases that were diagnosed between 2001 and 2010. Data were collected on patient and sample characteristics as well as results from immunophenotype and molecular studies. RESULTS In total, 168 serous effusions were identified from 110 patients. The most common site of involvement was the pleural cavity (n = 133) followed by the peritoneal cavity (n = 30) and pericardial cavity (n = 5). The volume of serous effusions ranged from 2 mL to 1000 mL (mean, 238 mL). In 42 patients (38.2%), serous effusions were the primary source of diagnosis. In 129 patients who had a diagnosis of LPD, either generic (n = 82) or specific (n = 47) ancillary tests were performed as a single test in 58 samples (67.4%) or as a combination of multiple studies in 19 samples (23.2%). Immunophenotyping was successful in almost all samples that had a specific subtype with 16 B-cell and 4 T-cell lymphomas being diagnosed. More samples with a specific subtype of lymphoma underwent molecular tests compared with those who had a generic diagnosis (19.1% vs 13.4%). CONCLUSIONS Successful, specific subtyping of lymphoproliferative disorders was achieved in approximately 33% of cases that were tested for ancillary studies following an approach for the triage and aliquoting of serous effusion samples. Cancer (Cancer Cytopathol) 2013;121:261–70. © 2012 American Cancer Society.

Expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) is important in predicting a response to targeted therapies in breast cancer. Immunohistochemical assays to determine hormone receptor (HR) and HER2 status must therefore be accurate and reproducible. Tissue fixation has been shown to play a crucial role in determining consistency in quality. Although guidelines impose upper limits for the fixation period, the data on which these limits are based are scant. This study aimed to prospectively examine the effect of fixation of >72 hours on these assays. In 101 invasive breast cancer samples, HR and HER2 status was compared between tumor blocks undergoing a short fixation period with those undergoing a period of prolonged fixation (PF). Discordances were classified as an incremental change between categories of (i) a single order of magnitude, that is a difference in the status of low positive (Allred score 3) compared with positive (Allred score 4 to 8) or negative (Allred score 0 or 2) and vice versa for HRs and a difference in HER2 status of equivocal compared with negative or positive and vice versa or (ii) greater than a single order of magnitude, that is a difference in the status of positive compared with negative or vice versa. The median fixation time for the short fixation group was 13 hours and 18 minutes (mean, 13 h 17 min; range, 10 h 33 min to 17 h 45 min) and for the PF group was 79 hours 22 minutes (mean, 79 h 35 min; range, 73 h 33 min to 102 h 30 min). Eight cases showed discordances, all of which were of a single order of magnitude including 1 for ER, 5 for PR, and 2 for HER2. In 6 of these, a higher score was seen in the PF group. In conclusion, fixation for limited periods beyond 72 hours does not result in a reduction in assay sensitivity in the determination of ER, PR, or HER2 immunohistochemical status.