Miracle-dz/UniFAR-FTUs huggingface dataset:
Endofin Recruits TOM1 to Endosomes*

Endofin is an endosomal protein implicated in regulating membrane trafficking. It is characterized by the presence of a phosphatidylinositol 3-phosphate-binding FYVE domain positioned in the middle of the molecule. To determine its potential effectors or binding partners, we used the carboxyl-terminal half of endofin as bait to screen a human brain cDNA library in a yeast two-hybrid system. Three clones that encode TOM1 were recovered. TOM1 is a protein closely related to the VHS (VPS-27, Hrs, and STAM) domain-containing GGA family. Although the function of the GGAs in mediating Golgi to lysosomal trafficking is well established, the subcellular localization and function of TOM1 remain unknown. Glutathione S-transferase pull-down assays as well as co-immunoprecipitation experiments confirmed that the carboxyl-terminal half of endofin binds specifically to the carboxyl-terminal region of TOM1. Neither SARA nor Hrs, two other FYVE domain proteins, interact with this region of TOM1. Moreover, endofin does not interact with the analogous region of two other members of the TOM1 protein family, namely, TOM1-like 1 (TOM1-L1) or TOM1-like 2 (TOM1-L2). The carboxyl-terminal region of TOM1 was used as immunogen to generate TOM1-specific antibody. This antibody can distinguish TOM1 from the other family members as well as coimmunoprecipitate endogenous endofin. It also revealed the primarily cytosolic distribution of TOM1 in a variety of cell types by immunofluorescence analyses. In addition, sucrose density gradient analysis showed that both TOM1 and endofin can be detected in cellular compartments marked by the early endosomal marker EEA1. A marked recruitment of TOM1 to endosomes was observed in cells overexpressing endofin or its carboxyl-terminal fragment, indicating TOM1 to be an effector for endofin and suggesting a possible role for TOM1 in endosomal trafficking.
A continuous common-source outbreak of campylobacteriosis associated with changes to the preparation of chicken liver pâté

SUMMARY In December 2006 an outbreak of Campylobacter infection occurred in Forth Valley, Scotland, affecting 48 people over a 3-week period. All cases dined at restaurant A. We conducted a cohort study in a party of 30 who ate lunch at restaurant A on 21 December to identify the vehicle of infection. Of 29 respondents, the attack rate in those who ate chicken liver pâté was 86% (6/7) compared to 0% (0/22) for those who did not. Between 1 December and 1.30 p.m. on 21 December the restaurant had used a different method of cooking the pâté. No cases reported dining at the restaurant after this time. The outbreak's duration suggested a continuous source. This is the first continuous source outbreak of Campylobacter documented in Scotland. Chicken liver pâté was the most likely vehicle of infection. This outbreak illustrates the hazards associated with undercooking Campylobacter-contaminated food.
Different Roles of CHOP and JNK in Mediating Radiation-Induced Autophagy and Apoptosis in Breast Cancer Cells

Unfolded protein response (UPR) is comprised of complex and conserved stress pathways that function as a short-term adaptive mechanism to reduce levels of unfolded or misfolded proteins and maintain homeostasis in the endoplasmic reticulum (ER). UPR can be triggered by prolonged or persistent ER stress under many physiological or pathological conditions, including radiation exposure. Radiation-induced ER stress elicits autophagy and apoptosis in cancer cells, where C/EBP homologous protein (CHOP) and c-Jun NH2-terminal kinase (JNK) may play crucial roles. However, the specific mechanisms that regulate autophagy and apoptosis through CHOP and JNK after radiation exposure and how the balance of these activities determines the cellular radiosensitivity remain largely unclear. In this study, we found that exposure to X-ray radiation induced ER stress, UPR and high expression of CHOP and JNK. Furthermore, autophagy and apoptosis occurred in sequential order when breast cancer MDA-MB-231 and MCF-7 cells were exposed to X-ray radiation. CHOP gene knockdown with RNA interference inhibited autophagy and enhanced radiosensitivity in MDA-MB-231 cells, while impacting apoptosis and subsequently increasing radioresistance in MCF-7 cells. However, treatment with JNK inhibitor decreased autophagy while promoting apoptosis, thereby leading to radiosensitivity in both cell lines. Our results indicate that CHOP mediates radiation-induced autophagy and apoptosis in a cellular environment. Importantly, the functional consistency of regulating apoptosis and autophagy in these two irradiated breast cancer cell lines suggests that JNK may be more useful as a potential target for maximizing the efficacy of radiation therapy for breast cancers.
p53-Dependent and -Independent Pathways of Apoptotic Cell Death in Sepsis1

Sepsis induces extensive apoptosis of lymphocytes, which may be responsible for the profound immune suppression of the disorder. Two potential pathways of sepsis-induced lymphocyte apoptosis, Fas and p53, were investigated. Lymphocyte apoptosis was evaluated 20–22 h after sepsis by annexin V or DNA nick-end labeling. Fas receptor-deficient mice had no protection against sepsis-induced apoptosis in thymocytes or splenocytes. p53 knockout mice (p53−/−) had complete protection against thymocyte apoptosis but, surprisingly, had no protection in splenocytes. p53−/− mice had no improvement in sepsis survival compared with appropriately matched control mice with sepsis. We conclude that both p53-dependent and p53-independent pathways of cell death exist in sepsis. This differential apoptotic response of thymocytes vs splenocytes in p53−/− mice suggests that either the cellular response or the death-inducing signal is cell-type specific in sepsis. The fact that p53−/− lymphocytes of an identical subtype (CD8−CD4+) were protected in thymi but not in spleens indicates that cell susceptibility to apoptosis differs depending upon other unidentified factors.
Variability for Leaf and Seed Glucosinolate Contents and Profiles in a Germplasm Collection of the Brassica juncea

Aim: A renewed interest in glucosinolates (GSLs) as compounds with biocidal and anticarcinogenic activity demands evaluation of the available variability in germplasm collections. The objective of the present study was to evaluate a germplasm collection of the Brassica juncea for total content and profile of leaf and seed GSLs. Methods: A total of 366 entries of a RIL population derived from cross of NUDH-YJ-04 and RL-1359, were nondestructively analyzed by near-infrared reflectance spectroscopy by means of previously developed calibration equations. Out of 366 lines, 97 lines were selected on the basis of glucosinolate range and further analyzed by ultra performance liquid chromatography for total GSL content and the concentrations of individual components i.e. sinigrin, glucoiberin, epiprogoitrin, gluconapin, gluconasturtiin and gluconeobrassicin. Results and conclusion: The collection contained great variability for GSL content and profile. Remarkable variation in glucosinolate content and profiles from different tissues within one plant may reflect different control mechanism operating on the glucosinolate biosynthetic pathway in different tissues. In the present study no correlation has been observed in leaf and seed glucosinolates. NIRS screening followed by further HPLC analyses on preselected entries led to a fast and comprehensive evaluation of variability for total content and profile of seed GSLs, which represents an important advance in the evaluation of GSLs in Brassica germplasm.
Lentiviral-Mediated Transcriptional Targeting of Dendritic Cells for Induction of T Cell Tolerance In Vivo1

Dendritic cells (DCs) are important APCs able to induce both tolerance and immunity. Therefore, DCs are attractive targets for immune intervention. However, the ex vivo generation and manipulation of DCs at sufficient numbers and without changing their original phenotypic and functional characteristics are major obstacles. To manipulate DCs in vivo, we developed a novel DC-specific self-inactivating lentiviral vector system using the 5′ untranslated region from the DC-STAMP gene as a putative promoter region. We show that a gene therapy approach with these DC-STAMP-lentiviral vectors yields long-term and cell-selective transgene expression in vivo. Furthermore, transcriptionally targeted DCs induced functional, Ag-specific CD4 and CD8 T cell tolerance in vivo, which could not be broken by viral immunization. Tolerized CTL were unable to induce autoimmune diabetes in a murine autoimmune model system. Therefore, delivering transgenes specifically to DCs by using viral vectors might be a promising tool in gene therapy.
CORPORATE GOVERNANCE STRUCTURES AND STOCK RETURNS: EVIDENCE FROM THE STOCK EXCHANGE OF THAILAND (โครงสร้างบรรษัทภิบาลกับราคาหุ้น กรณีศึกษา บริษัทในตลาดหลักทรัพย์แห่งประเทศไทย)

Abstract The purpose of this research is to examine the relationship of corporate governance practices of the firm and its stock performance on the Stock Exchange of Thailand (SET). The sample included non-financial firms listed on the SET (2014-2015) (n = 257 firms). Data was collected from the SET’s SETSMART database, including stock return information and corporate governance and ownership structure information. The predictor variables included board structure variables (board size, CEO duality, board independence, gender diversity, meeting frequency, & CEO compensation) and ownership structure variables (family ownership, institutional ownership, & ownership concentration). The multiple regression model was relatively weak (R 2 = .141). Gender diversity showed a strong positive effect on stock returns, while the effects of board size (negative) and institutional ownership (positive) were weaker. The implication is that these elements of corporate governance do not have a strong effect on stock returns in Thailand. Keywords: Corporate Governance, Stock Returns, Agency Theory บทคดยอ งานวจยนมวตถประสงคเพอทดสอบความสมพนธระหวางหลกการกำกบดแลกจการของกลมตวอยางและราคาหนในตลาดหลกทรพยแหงประเทศไทย กลมตวอยาง ไดแก กลมตวอยางทไมใชสถาบนการเงนและมรายชอในตลาดหลกทรพยแหงประเทศไทย (ในป ค.ศ. 2014 – 2015) (n = 257 ตวอยาง) โดยรวบรวมขอมลจากฐานขอมล SETSMART รวมทงขอมลผลตอบแทนหนและขอมลการกำกบดแลกจการและโครงสรางการถอหน ตวแปรพยากรณ ประกอบดวย ตวแปรโครงสรางของคณะกรรมการ (ขนาดคณะกรรมการ, การควบตำแหนงประธานกรรมการกบ CEO, สดสวนกรรมการอสระ, ความแตกตางทางดานเพศ, ความถในการประชม และคาตอบแทนผบรหาร) และตวแปรโครงสรางการถอหน (การถอหนแบบครอบครว, การถอหนแบบสถาบน และ การถอหนแบบกระจกตว) ผลการวเคราะหการถดถอยพหคณ พบวา มความสมพนธระหวางตวแปรนอย (R 2 = .141) ความแตกตางทางดานเพศของคณะกรรมการ มผลกระทบเชงบวกตอผลตอบแทนหนในระดบสง ในขณะทผลกระทบดานขนาดคณะกรรมการ (เชงลบ) และการถอหนแบบสถาบน (เชงบวก) มผลกระทบตอผลตอบแทนหนในระดบนอย การนำผลวจยครงนไปใช คอ องคประกอบของการกำกบดแลกจการไมมผลกระทบในระดบสงทสงผลตอผลตอบแทนหนในประเทศไทย คำสำคญ : การกำกบดแลกจการ ผลตอบแทนหน ทฤษฎหนวยงาน
Neural Synaptic Weighting With a Pulse-Based Memristor Circuit

A pulse-based programmable memristor circuit for implementing synaptic weights for artificial neural networks is proposed. In the memristor weighting circuit, both positive and negative multiplications are performed via a charge-dependent Ohm's law (). The circuit is composed of five memristors with bridge-like connections and operates like an artificial synapse with pulse-based processing and adjustability. The sign switching pulses, weight setting pulses and synaptic processing pulses are applied through a shared input terminal. Simulations are done with both linear memristor and window-based nonlinear memristor models.
THE INFLUENCE OF AUDIT COMMITTEE CHARACTERISTIC TO AUDIT LAG ON FINANCIAL REPORTING (Empirical study on Company Listed on The Indonesia Stock Exchange Year 2013)

The purpose of this research is to analyze factors that influences timeliness submission of the Indonesian public company’s financial report. The examined factors of this research are audit committee characteristic, which are audit committee independence, audit committee expertise, audit committee size, and audit committee meeting as independence variable while timeliness as dependent variable. The data that used in this research was the secondary data and selected by using purposive sampling method. The sample consist of 288 companies listed in Indonesia Stock Exchange (IDX) and sent the financial report to BAPEPAM in 2013. The analysis to test the hypothesis is using logistic regression at level significant 5%. The result of this research shows that audit committee size and audit committee meeting have significant influence to reduce audit report lag, while the audit committee independence and audit committee expertise do not have significant influence on the timeliness submission on financial reporting. Keyword: Audit Committee, Corporate Governance, Audit Lag.
Tomatoes, Lycopene, and Prostate Cancer

Summary The epidemiologic data tend to support an association between intake of tomato-based foods and a lower risk of prostate cancer. The observed inverse association may be due to lycopene though this is unproven at this point. Even two servings a week of a rich source of bioavailable lycopene, such as tomato sauce, was related to a substantially lower risk of prostate cancer. Whereas chance alone is highly unlikely to account for the consistent inverse association with tomato-based products, confounding by other variables, particularly dietary, cannot be definitively excluded as alternative explanations. Of greatest concern is that a lycopene-rich diet is acting as an indicator of a diet rich in vegetables and fruits that may lower risk of prostate cancer through other phytochemicals. An important historical lesson is provided by β-carotene, for which an abundance of evidence based on questionnaires and blood levels suggested a benefit on various cancers (93), particularly lung cancer, but recent intervention trials of β-carotene supplementation have not confirmed this benefit (60). In retrospect it appears difficult, if not impossible to differentiate β-carotene intake from that of a general dietary pattern that is high in fruits and vegetables. In contrast, this is not the case for lycopene. Other carotenoids in prostate tissue tend to be significantly interrelated, but lycopene content does not appear to be correlated appreciably with other carotenoids (83). In the Health Professionals Follow-Up Study and the Seventh-Day Adventist study, tomato-based products and lycopene were associated with a lower prostate cancer risk, but fruits and vegetables, individually and in aggregate, and other carotenoids were not associated with prostate cancer risk. These results are consistent with findings from other studies that overall vegetable and fruit consumption appear unrelated to prostate cancer incidence (36, 94, 95). It is more difficult to separate specific effects of lycopene from that of other potentially beneficial compounds in tomatoes; however, based on similarity of results for plasma predictors of lycopene with predictors of prostate cancer risk, the putative compound would be expected to have similar bioavailability characteristics as lycopene. Thus, with regard to practical recommendations, the available data are most conservatively interpreted as supporting a potential benefit of increased consumption of tomatoes and tomato-based products. To attribute a specific effect to lycopene or a particular isomer of this carotenoid would require much more research. Additional studies by epidemiologists, clinical investigators, cancer biologists, and nutritional scientists are underway, and answers to many questions concerning tomatoes, lycopene, and prostate cancer should be forthcoming.
Does Increased Experience with Tissue Oximetry Monitoring in Microsurgical Breast Reconstruction Lead to Decreased Flap Loss? The Learning Effect

Background: Early studies have shown that near-infrared monitoring with tissue oximetry shows promise in providing earlier detection of free flap vascular compromise. However, large-scale clinical evaluation of this technology on flap outcome has not previously been established. This study examines the effect of tissue oximetry on flap reexploration rates and salvage over a 10-year period. The learning curve for this new technology is also assessed. Methods: A retrospective review was performed of prospectively maintained data on all microsurgical breast reconstructions performed at an academic institution from 2004 to 2014. Patients were divided into two separate cohorts—standard clinical monitoring and standard clinical monitoring plus tissue oximetry—and rates of reexploration and flap salvage were compared. Subgroup analysis (tertiles) was performed to assess outcomes with increasing experience. Results: A total of 380 flaps (36.2 percent) received standard clinical monitoring, and 670 flaps (63.8 percent) received additional tissue oximetry monitoring. The rate of flap salvage before implementation of tissue oximetry monitoring was 57.7 percent and increased to 96.6 percent (p < 0.001). The number of complete flap losses decreased from 11 (2.9 percent) to one (0.1 percent) with the use of tissue oximetry (p < 0.001). Subgroup analysis demonstrated significantly fewer reexplorations in the third tertile. Conclusions: Inclusion of continuous tissue oximetry in the postoperative monitoring protocol of microsurgical breast reconstruction is associated with significantly improved salvage rates and fewer flap losses. Furthermore, learning curve assessment demonstrates that use of tissue oximetry can decrease the rate of reexploration over time.
R&D and the Rising Foreign Profitability of U.S. Multinational Corporations

We investigate how R&D contributes to rising foreign profitability in U.S. multinational corporations through wage and tax incentives. Our results suggest that wage savings increase foreign profit margins derived from foreign R&D, while tax incentives increase foreign profit margins derived from domestic R&D. By exploring their relative importance, we find that wage savings are more important than tax incentives in explaining foreign profit margins when the wage discount substantially exceeds tax incentives, and vice versa. Cross-sectional tests show that firms respond more to foreign R&D wage savings when they have access to local human talent, but less as the cost of conducting foreign R&D increases. Firms respond less to tax incentives to shift income derived from domestic R&D as transfer pricing risk increases. Our evidence sheds light on the importance of R&D-related income shifting that potentially separates the location of economic activity from the location of income. JEL Classifications: H25; H26.
Widefield quantitative multiplex surface enhanced Raman scattering imaging in vivo

Abstract. In recent years numerous studies have shown the potential advantages of molecular imaging in vitro and in vivo using contrast agents based on surface enhanced Raman scattering (SERS), however the low throughput of traditional point-scanned imaging methodologies have limited their use in biological imaging. In this work we demonstrate that direct widefield Raman imaging based on a tunable filter is capable of quantitative multiplex SERS imaging in vivo, and that this imaging is possible with acquisition times which are orders of magnitude lower than achievable with comparable point-scanned methodologies. The system, designed for small animal imaging, has a linear response from (0.01 to 100 pM), acquires typical in vivo images in <10 s, and with suitable SERS reporter molecules is capable of multiplex imaging without compensation for spectral overlap. To demonstrate the utility of widefield Raman imaging in biological applications, we show quantitative imaging of four simultaneous SERS reporter molecules in vivo with resulting probe quantification that is in excellent agreement with known quantities (R2>0.98).
Premature edge breakdown prevention techniques in CMOS APD fabrication

In this paper we have introduced the most popular applied premature edge breakdown prevention (PEBP) techniques and proposed a new practical and efficient design procedure technique to design a functional avalanche photodiode using standard CMOS process based on our design, simulation and fabrication experiences. The device simulations are used to find the best dimensional values minimizing PEB. Three proposed PEBP techniques are emerged from a systematic study aimed at miniaturization, while optimizing the overall performance. Based on the experimental results gained from the fabrication of a p-well and p-sub guard-rings a new n-well guard-ring PEBP technique is introduced and its performance is evaluated using the device simulation. It exhibits a dark count rate of 1 kHz (with 0.5V excess bias at room temperature), a maximum photon detection probability of 70% at maximum excess bias and 9V breakdown voltage.
Comparing RF linearity of npn and pnp SiGe HBTs

The RF linearity characteristics of complementary (npn + pnp) SiGe HBTs are investigated with respect to bias and frequency dependence, for the first time. The differences in distortion performance between npn and pnp SiGe HBTs are examined. Overall, at low bias currents (e.g., for minimum RF noise), both devices exhibit similar linearity performance and power gain, while for higher bias currents (e.g., for maximum gain), the pnp SiGe HBT offers advantages over the npn SiGe HBT. The linearity of both the npn and the pnp SiGe HBTs in common-emitter configuration improves as operating frequency rises.
Generation and Characterization of Telomere Length Maintenance in Tankyrase 2-Deficient Mice

ABSTRACT Telomere length and function are crucial factors that determine the capacity for cell proliferation and survival, mediate cellular senescence, and play a role in malignant transformation in eukaryotic systems. The telomere length of a specific mammalian species is maintained within a given range by the action of telomerase and telomere-associated proteins. TRF1 is a telomere-associated protein that inhibits telomere elongation by its binding to telomere repeats, preventing access to telomerase. Human TRF1 interacts with tankyrase 1 and tankyrase 2 proteins, two related members of the tankyrase family shown to have poly(ADP-ribose) polymerase activity. Human tankyrase 1 is reported to ADP-ribosylate TRF1 and to down-regulate the telomeric repeat binding activity of TRF1, resulting in telomerase-dependent telomere elongation. Human tankyrase 2 is proposed to have activity similar to that of tankyrase 1, although tankyrase 2 function has been less extensively characterized. In the present study, we have assessed the in vivo function of mouse tankyrase 2 by germ line gene inactivation and show that inactivation of tankyrase 2 does not result in detectable alteration in telomere length when monitored through multiple generations of breeding. This finding suggests that either mouse tankyrases 1 and 2 have redundant functions in telomere length maintenance or that mouse tankyrase 2 differs from human tankyrase 2 in its role in telomere length maintenance. Tankyrase 2 deficiency did result in a significant decrease in body weight sustained through at least the first year of life, most marked in male mice, suggesting that tankyrase 2 functions in potentially telomerase-independent pathways to affect overall development and/or metabolism.