Miracle-dz/UniFAR-FTUs huggingface dataset:
Apoptosis-linked Gene-2 (ALG-2)/Sec31 Interactions Regulate Endoplasmic Reticulum (ER)-to-Golgi Transport

Background: Whether ER to Golgi transport requires calcium, the source of calcium, and its mechanism is unknown. Results: A requirement for luminal calcium is demonstrated, and evidence is presented for a molecular effector pathway. Conclusion: Luminal calcium may regulate transport by activating these protein interactions. Significance: The described calcium effector pathway may lead to greater insight into calcium action at multiple transport steps. Luminal calcium released from secretory organelles has been suggested to play a regulatory role in vesicle transport at several steps in the secretory pathway; however, its functional roles and effector pathways have not been elucidated. Here we demonstrate for the first time that specific luminal calcium depletion leads to a significant decrease in endoplasmic reticulum (ER)-to-Golgi transport rates in intact cells. Ultrastructural analysis revealed that luminal calcium depletion is accompanied by increased accumulation of intermediate compartment proteins in COPII buds and clusters of unfused COPII vesicles at ER exit sites. Furthermore, we present several lines of evidence suggesting that luminal calcium affected transport at least in part through calcium-dependent interactions between apoptosis-linked gene-2 (ALG-2) and the Sec31A proline-rich region: 1) targeted disruption of ALG-2/Sec31A interactions caused severe defects in ER-to-Golgi transport in intact cells; 2) effects of luminal calcium and ALG-2/Sec31A interactions on transport mutually required each other; and 3) Sec31A function in transport required luminal calcium. Morphological phenotypes of disrupted ALG-2/Sec31A interactions were characterized. We found that ALG-2/Sec31A interactions were not required for the localization of Sec31A to ER exit sites per se but appeared to acutely regulate the stability and trafficking of the cargo receptor p24 and the distribution of the vesicle tether protein p115. These results represent the first outline of a mechanism that connects luminal calcium to specific protein interactions regulating vesicle trafficking machinery.
The Effect of Increasing Age on Thiopental Disposition and Anesthetic Requirement

The dose of thiopental required to induce anesthesia in adults decreases with age. The pharmacokinetic and pharmacodynamic properties of thiopental were studied in two groups of surgical patients to determine the mechanism of this decrease. In one group (29 patients 19–88 yr of age), thiopental was infused at a demonstrated early burst suppression (phase III). Arterial blood samples were obtained frequently during and after the infusion to measure serum thiopental concentrations, and power spectral analysis was used to calculate the spectral edge (Hz), defined as the frequency below which 95% of the EEG power is located. Pharmacodynamic modeling was used to relate the serum thiopental concentrations to the spectral edge in order to estimate the individual patient's brain sensitivity to thiopental. In a second group (28 patients 24–88 yr of age), pharmacokinetics were determined after a bolus or rapid infusion of thiopental. Arterial blood samples were obtained frequently to characterize the initial distribution phases, sampling continued for 24–48 h to characterize elimination processes.The dose of thiopental required to achieve early burst suppression on the electroencephalogram (EEG) decreased linearly and significantly with age. Pharmacodynamic modeling also demonstrated that brain sensitivity to thiopental does not change with age. The age-related decrease of the thiopental dose requirement is due to a change in the initial distribution of the drug. That is, the initial distribution volume (central compartment, or V1) of thiopental decreases exponentially with age. This smaller initial distribution volume in the elderly results in higher serum levels after a given dose of thiopental.
Urticaria associated with thyrotoxicosis

We report a patient with chronic urticaria which was closely associated with elevated levels of thyroxine. The urticaria responded poorly to antihistamines and only partially to systemic steroids, but resolved consistently when the thyroxine level was reduced to normal. The mechanism for the association may involve modulation of the cyclic AMP levels within mast cells.
A Cross-Cancer Genetic Association Analysis of the DNA Repair and DNA Damage Signaling Pathways for Lung, Ovary, Prostate, Breast, and Colorectal Cancer

Background: DNA damage is an established mediator of carcinogenesis, although genome-wide association studies (GWAS) have identified few significant loci. This cross-cancer site, pooled analysis was performed to increase the power to detect common variants of DNA repair genes associated with cancer susceptibility. Methods: We conducted a cross-cancer analysis of 60,297 single nucleotide polymorphisms, at 229 DNA repair gene regions, using data from the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) Network. Our analysis included data from 32 GWAS and 48,734 controls and 51,537 cases across five cancer sites (breast, colon, lung, ovary, and prostate). Because of the unavailability of individual data, data were analyzed at the aggregate level. Meta-analysis was performed using the Association analysis for SubSETs (ASSET) software. To test for genetic associations that might escape individual variant testing due to small effect sizes, pathway analysis of eight DNA repair pathways was performed using hierarchical modeling. Results: We identified three susceptibility DNA repair genes, RAD51B (P < 5.09 × 10−6), MSH5 (P < 5.09 × 10−6), and BRCA2 (P = 5.70 × 10−6). Hierarchical modeling identified several pleiotropic associations with cancer risk in the base excision repair, nucleotide excision repair, mismatch repair, and homologous recombination pathways. Conclusions: Only three susceptibility loci were identified, which had all been previously reported. In contrast, hierarchical modeling identified several pleiotropic cancer risk associations in key DNA repair pathways. Impact: Results suggest that many common variants in DNA repair genes are likely associated with cancer susceptibility through small effect sizes that do not meet stringent significance testing criteria. Cancer Epidemiol Biomarkers Prev; 25(1); 193–200. ©2015 AACR.
The analyses of risk factors for COPD in the Li ethnic group in Hainan, People’s Republic of China

Objective To study the risk factors for chronic obstructive pulmonary disease (COPD) in Li population in Hainan province, People’s Republic of China. Methods Li people above 40 years of age from Hainan were chosen by stratified random cluster sampling between 2012 and 2014. All participants were interviewed with a home-visiting questionnaire, and spirometry was performed on all eligible participants. Patients with airflow limitation (forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] <0.70) were further examined by postbronchodilator spirometry, and those with a postbronchodilator FEV1/FVC <0.70 was diagnosed with COPD. The information of physical condition and history, smoking intensity, smoking duration, second-hand smoking, education, job category, monthly household income, working years, residential environment, primary fuel for cooking and heating (biomass fuel including wood, crop residues, dung, and charcoal, or modern fuel such as natural gas, liquefied petroleum gas, electricity, and solar energy), ventilated kitchen, heating methods, air pollution, recurrent respiratory infections, family history of respiratory diseases, cough incentives, and allergies of COPD and non-COPD subjects was analyzed by univariate and multivariate logistic regression models to identify correlated risk factors for COPD. Results Out of the 5,463 Li participants, a total of 277 COPD cases were identified by spirometry, and 307 healthy subjects were randomly selected as controls. Univariate logistic regression analyses showed that older people (65 years and above), low body mass index (BMI), biomass smoke, 11–20 and >20 cigarettes/day, smoking for 40 years or more, second-hand smoking, recurrent respiratory infections, and induced cough were risk factors for COPD, whereas high BMI, high education level, and presence of ventilated kitchen were protective factors. Subsequent multivariate logistic regression model further demonstrated that aging, low BMI, biomass smoke, >20 cigarettes/day, and recurrent respiratory tract infections were high-risk factors for COPD in the Li population. Conclusion The incidence of COPD has a strong correlation with age, BMI, biomass smoke, >20 cigarettes/day, and recurrent respiratory infections, suggesting they were high-risk factors for COPD in Li population.
Staging of Argyrophilic Grains: An Age‐Associated Tauopathy

We have reported that the ambient gyrus is the site with the greatest accumulation of argyrophilic grains (AGs) and that the degeneration of the ambient gyrus is responsible for dementia with grains. Here we analyzed 1,405 serial autopsy cases from 2 hospitals and detected AGs only in cases older than 56 years of age. The distribution of AGs followed a stereotypic regional pattern. Thus, we propose the following staging paradigm: stage I: AGs restricted to the ambient gyrus and its vicinity; stage II: AGs more apparent in the anterior and posterior medial temporal lobe, including the temporal pole, as well as the subiculum and entorhinal cortex; and stage III: abundant AGs in the septum, insular cortex, and anterior cingulate gyrus, accompanying spongy degeneration of the ambient gyrus. Sixty-three of 65 (96.9%) argyrophilic grain stage III cases without other dementing pathology were classified as 0.5 or higher in the clinical dementia rating. Forty-seven of 50 dementia with grains cases (94%) were stage III and 3 were stage II. No association with apoE genotyping was detected. Our study further confirms that dementia with grains is an age-associated tauopathy with relatively uniform distribution and may independently contribute to cognitive decline in the elderly.
Joint Network-Channel Coding for the Multiple-Access Relay Channel

We propose to use joint network-channel coding based on turbo codes for the multiple-access relay channel. Such a system can be used for the cooperative uplink for two mobile stations to a base station with the help of a relay. We compare the proposed system with a distributed turbo code for the relay channel and with a system which uses separate network-channel coding for the multiple-access relay channel. Simulation results confirm that the systems with network coding for the multiple-access relay channel gain cooperative diversity compared to the system with the distributed turbo code for the relay channel. Moreover, the results show that joint network-channel coding outperforms separate network-channel coding. The reason for this is that the redundancy which is contained in the transmission of the relay can be exploited more efficiently with joint network-channel coding
Malignant Transformation and Stromal Invasion from Normal or Hyperplastic Tissues: True or False?

Carcinogenesis is believed to be a multi-step process, progressing sequentially from normal to hyperplastic, to in situ, and to invasive stages. A number of studies, however, have detected malignancy-associated alterations in normal or hyperplastic tissues. As the molecular profile and clinical features of these tissues have not been defined, the authors invited several well-recognized pathologist, oncologists, biologist, surgeons, and molecular biologist to offer their opinion on: (1) whether these tissues belong to a previously unrevealed malignant entity or focal alterations with no significant consequence? (2) whether these alterations are linked to early onset of cancer or cancer of unknown primary site, and (3) how to further define these lesions?
Characterization of an adaptive immune response in microsatellite-instable colorectal cancer

Sporadic or hereditary colorectal cancer (CRC) with microsatellite instability (MSI) is frequently characterized by inflammatory lymphocytic infiltration and tends to be associated with a better outcome than microsatellite stable (MSS) CRC, probably reflecting a more effective immune response. We investigated inflammatory mechanisms in 48 MSI CRCs and 62 MSS CRCs by analyzing: (1) the expression of 48 cytokines using Bio-Plex multiplex cytokine assays, and (2) the in situ immune response by immunohistochemical analysis with antibodies against CD3 (T lymphocytes), CD8 (cytotoxic T lymphocytes), CD45RO (memory T lymphocytes), T-bet (Th1 CD4 cells), and FoxP3 (regulatory T cells). MSI CRC exhibited significantly higher expression of CCL5 (RANTES), CXCL8 (IL-8), CXCL9 (MIG), IL-1β, CXCL10 (IP-10), IL-16, CXCL1 (GROα), and IL-1ra, and lower expression of MIF, compared with MSS CRC. Immunohistochemistry combined with image analysis indicated that the density of CD3+, CD8+, CD45RO+, and T-bet+ T lymphocytes was higher in MSI CRC than in MSS CRC, whereas the number of regulatory T cells (FoxP3+) was not statistically different between the groups. These results indicate that MSI CRC is associated with a specific cytokine expression profile that includes CCL5, CXCL10, and CXCL9, which are involved in the T helper type 1 (Th1) response and in the recruitment of memory CD45RO+ T cells. Our findings highlight the major role of adaptive immunity in MSI CRC and provide a possible explanation for the more favorable prognosis of this CRC subtype.
Three Essays on Decision Making Strategies

This dissertation consists of three essays on decision making strategies. In the first essay, we analyze the determinants of expansions and contractions of shopping centers using a unique dataset of property level data for shopping centers in eleven metropolitan areas over the period from 1995 through 2005. We find that shopping centers with large operating costs are less likely to expand and are more likely to contract. Higher expected revenue increases the likelihood of expansion and decreases the likelihood of contraction. We find weak support for Grenadier’s theory that a larger number of competitors reduces the value of option to wait and increases the likelihood of both expansion and contraction. The market share of competitors reduces the likelihood of increasing the number of stores as suggested by the theory of strategic positioning. In the second essay, we examine the intra-metropolitan location decisions of retail stores by focusing on the opening of a comprehensive list of department (“anchor”) stores in the United States. The nonparametric K-density procedure shows that new stores are more dispersed than existing stores; their locations depend on existing competitive conditions. By applying a conditional logit model (CLM), we find that the location choices of new anchors can be explained by zoning, population, CBD and highway proximity, potential revenue and revenue growth, cannibalization, competition and localization economies. The CLM-based K-density confidence intervals effectively explain actual location patterns within three miles. In the third essay, we find that the probability of intentional accounting misstatements (irregularities) increases with the level of investor beliefs about business conditions but decreases when the beliefs are sufficiently positive. Further, the proportion of independent directors with Tingyu Zhou – University of Connecticut, 2014 accounting expertise is a decreasing function of investor beliefs, and the likelihood of irregularities is decreasing in the proportion of independent directors with accounting expertise. Finally, stock market reaction to accounting restatements is positively related to the proportion of independent directors with accounting expertise. These findings underscore the effectiveness of accounting expertise of independent directors in reducing the incidence and severity of corporate
Fault tolerant logic cell FPGA

It is proposed fault tolerant logic cell — LUT FPGA according to concept of the functionally complete tolerant element (FCT). The FCT element (logic element with the redundancy basis) retains functional completeness in case of faults. FCT element allows to perform FPGA self-repair after faults. It is established, that in a number of cases the quadrupling of the LUT's transistors has more advantages than the tripling.
Alternative female portrayals in movies: The impact of strong animated women on the viewing audience.

There has been an observable increase of alternative female leading characters that possess non-stereotypical attributes in animation. It has been shown in previous research that stereotypical female portrayals are capable of influencing notions and perceptions held on women by viewers (Calvert & Huston, 1987). Considering this societal impact, it is important to investigate these portrayals as well as developments thereof. Research on this topic, has been considerably lacking in respect of the most current alternative female portrayals and audience effects, especially regarding animation. Most studies that have touched upon this particular subject have been performed more than a decade ago and were geared towards the effects of stereotypes rather than those of non-stereotypical characters. This study was hence affiliated with uncovering audience effects of alternative animated female characters. An experimental study was performed in which two separate research groups were subjected to animated videos that contained stereotypical or non-stereotypical female characters. After viewing, the respondents had to fill out survey questions enquiring about their prejudice towards women, mood and levels of self-objectification. Results showed no effects regarding the displayed female character and prejudice against women, nor were there effects concerning self-objectification. Respondents who viewed non-stereotypical content, however, did show a significant increase in positive mood, whereas those who viewed stereotypical content showed a decrease. Male respondents also showed significantly more prejudice towards women and a significantly larger decline in positive mood than female respondents. This study managed to add some updated knowledge to the current field that could inspire further study into the effects of media content on mood and the effects of gender on prejudice.
Solubility and fluoride release in ionomers and compomers.

OBJECTIVE The degree of solubility and the fluoride release of glass-ionomer cements and "compomers" were determined as a function of time. METHOD AND MATERIALS Three conventional glass-ionomer cements, three hybrid ionomers, and two compomers were included in the study. Disk-shaped specimens were prepared and immersed in a lactic acid solution. Solubility was evaluated from determinations of loss of mass as a function of time. To evaluate fluoride release, similar specimens were immersed in 50 mL of deionized water to which 50 mL of buffer solution was added. A fluoride ion detector was used to read the concentration of fluoride ion in the overall solution at different times after immersion. RESULTS Material and time factors had a significant influence on results. The compomers showed less corrosion and fluoride release than the ionomers. Some correlation was found between solubility and fluoride leakage values. CONCLUSION Components of both the ionomers and compomers that were studied can dissolve in water. The materials leak fluoride ions in amounts that differ according to the characteristics of the individual products.
Small group discussion followed by presentation as a revision exercise at the end of a teaching module in biochemistry.

BACKGROUND We evaluated the effect of student-dominated small group discussion followed by faculty-moderated presentation as a revision exercise after completion of a teaching module in biochemistry. We assessed the understanding of graduate medical students on the topic and the gain in retention of information, if any, after 15 days. METHODS Small group discussions involving 11-12 students in each group were conducted on 12 application-oriented problems in 'amino acid metabolism'. A group leader among the students helped to conduct the discussions. While two-thirds of the problems were taken up after the discussion during faculty- or student-moderated interactive presentations, the remaining were not. The effects on low-, medium- and high achievers were evaluated by a pre-test and post-test with multiple choice questions immediately after the session. A subjective feedback was also obtained. To test short-term memory, a post-test with the same multiple choice questions was conducted after 15 days. RESULTS The exercise was effective and equally beneficial for low-, medium- and high achievers. The gain was maximum when faculty moderated the presentation session. The students' retention of their gain after 15 days was complete. All the students wanted more such sessions in future. CONCLUSION Student-dominated small group discussion followed by a faculty-moderated presentation is an effective, revision exercise for undergraduate medical students.
Improved Bounds on Nonblocking 3-Stage Clos Networks

We consider a generalization of edge coloring bipartite graphs in which every edge has a weight in $[0,1]$ and the coloring of the edges must satisfy that the sum of the weights of the edges incident to a vertex $v$ of any color must be at most 1. For unit weights, Konig's theorem says that the number of colors needed is exactly the maximum degree. For this generalization, we show that $2.557 n + o(n)$ colors are sufficient, where $n$ is the maximum total weight adjacent to any vertex, improving the previously best bound of $2.833n+O(1)$ due to Du et al. Our analysis is interesting on its own and involves a novel decomposition result for bipartite graphs and the introduction of an associated continuous one-dimensional bin packing instance which we can prove allows perfect packing. This question is motivated by the question of the rearrangeability of 3-stage Clos networks. In that context, the corresponding parameter $n$ of interest in the edge coloring problem is the maximum over all vertices of the number of unit-sized bins needed to pack the weights of the incident edges. In that setting, we are able to improve the bound to $2.5480 n + o(n)$, also improving a bound of $2.5625n+O(1)$ of Du et al. We also consider the online version of this problem in which edges have to be colored as soon as they are revealed. In this context, we can show that $5n$ colors are enough. This contrasts with the best known lower bound of $3n-2$ by Tsai, Wang, and Hwang but improves upon the previous best upper bound of $5.75n$ obtained by Gao and Hwang. Additionally, we show several improved bounds for more restricted versions of the problem. These online bounds are achieved by simple and easy-to-implement algorithms, inspired by the first fit heuristic for bin packing.