Miracle-dz/UniFAR-FTUs huggingface dataset:
iTRAQ Analysis of Complex Proteome Alterations in 3xTgAD Alzheimer's Mice: Understanding the Interface between Physiology and Disease

Alzheimer's disease (AD) is characterized by progressive cognitive impairment associated with accumulation of amyloid β-peptide, synaptic degeneration and the death of neurons in the hippocampus, and temporal, parietal and frontal lobes of the cerebral cortex. Analysis of postmortem brain tissue from AD patients can provide information on molecular alterations present at the end of the disease process, but cannot discriminate between changes that are specifically involved in AD versus those that are simply a consequence of neuronal degeneration. Animal models of AD provide the opportunity to elucidate the molecular changes that occur in brain cells as the disease process is initiated and progresses. To this end, we used the 3xTgAD mouse model of AD to gain insight into the complex alterations in proteins that occur in the hippocampus and cortex in AD. The 3xTgAD mice express mutant presenilin-1, amyloid precursor protein and tau, and exhibit AD-like amyloid and tau pathology in the hippocampus and cortex, and associated cognitive impairment. Using the iTRAQ stable-isotope-based quantitative proteomic technique, we performed an in-depth proteomic analysis of hippocampal and cortical tissue from 16 month old 3xTgAD and non-transgenic control mice. We found that the most important groups of significantly altered proteins included those involved in synaptic plasticity, neurite outgrowth and microtubule dynamics. Our findings have elucidated some of the complex proteome changes that occur in a mouse model of AD, which could potentially illuminate novel therapeutic avenues for the treatment of AD and other neurodegenerative disorders.
Hindcast skill improvement in Climate Forecast System (CFSv2) using modified cloud scheme

Two sets of CFSv2 retrospective forecast experiments are performed to check the model's fidelity for operational forecast usage for the prediction of Indian summer monsoon rainfall (ISMR). The first experiment (Exp1) is identical to the present operational mode of the model. The second experiment (Exp2) includes major changes in terms of the different cumulus parameterization scheme, modified cloud microphysics scheme and the variable critical relative humidity. These changes have already shown enhancement in the seasonal viability of the model in the free‐run mode. This study has carried out exclusive hindcast experiments by combining the above mentioned major changes. There is a marked improvement in the spatial distribution of the precipitation and the amplitude of the annual cycle of ISMR. The underestimation of the peak of the annual cycle of ISMR in Exp1 is enhanced by 23% in Exp2. Because of better simulations of clouds and tropospheric temperature gradient, the point of maximum precipitation has migrated northwards from equator (Exp1) to 20°N (Exp2). These improvements also impress upon all the other aspect of the ocean–atmosphere coupled interaction, namely planetary‐scale Hadley circulation, air–sea interactions and most of the facets of monsoon teleconnections. The skill of extended Indian monsoon rainfall region (65°–95°E, 5°–35 N) has increased from 0.50 in Exp1 to 0.67 in Exp2 and the same holds true for other regions as well. The skill of Niño3. 4 index enhances from 0.58 in Exp1 to 0.67 in Exp2. The dynamical wind shear based monsoon performance indices also show the surge in the skill score. The significant improvement of seasonal skill scores across all the variables clearly shows the dynamical consistency and at the same time establishes the superiority of the Exp2 for seasonal forecast. This work will add new dimension to develop a new genre of monsoon forecasting model.
Throughput and Energy Efficiency Analysis of Small Cell Networks with Multi-Antenna Base Stations

Small cell networks have recently been proposed as an important evolution path for the next-generation cellular networks. However, with more and more irregularly deployed base stations (BSs), it is becoming increasingly difficult to quantify the achievable network throughput or energy efficiency. In this paper, we develop an analytical framework for downlink performance evaluation of small cell networks, based on a random spatial network model, where BSs and users are modeled as two independent spatial Poisson point processes. A new simple expression of the outage probability is derived, which is analytically tractable and is especially useful with multi-antenna transmissions. This new result is then applied to evaluate the network throughput and energy efficiency. It is analytically shown that deploying more BSs can always increase the network throughput, but the throughput will scale with the BS density first linearly, then logarithmically, and finally converge to a constant. On the other hand, increasing the number of BS antennas can decrease the outage probability exponentially, thus can always increase the network throughput. However, increasing the BS density or the number of transmit antennas will first increase and then decrease the energy efficiency if the non-transmission power or the circuit power consumption is less than certain thresholds, and the optimal BS density and the optimal number of BS antennas can be found. Otherwise, the energy efficiency will always decrease. Simulation results shall demonstrate that our conclusions based on the random network model are general and also hold in a regular grid-based model.
Plasminogen activator inhibitor-1 gene is associated with major depression and antidepressant treatment response

Objective Evidence suggests that plasminogen activator inhibitor type 1 gene (SERPINE1) is a stress-related gene and serum plasminogen activator inhibitor type 1 levels are increased in patients with major depressive disorders (MDD). Methods To investigate whether common genetic variation in the SERPINE1 gene is associated with MDD and the therapeutic response to antidepressants, six polymorphisms (rs2227631, rs1799889, rs6092, rs6090, rs2227684 and rs7242) of the SERPINE1 gene were genotyped in 188 Chinese MDD patients and 346 controls. Among the MDD patients, 140 accepted selective serotonin reuptake inhibitor (fluoxetine or citalopram) antidepressant treatment for 4 weeks with therapeutic evaluation before and after. Results In single-marker-based analysis, the rs2227684-G and rs7242-T alleles were more frequent in MDD patients than in controls (P=0.010 and 0.010, respectively). The haplotype derived from the rs6090-G, rs2227684-G and rs7242-T polymorphisms was 1.19-fold higher in patients with MDD than in controls (P=0.0038). Haplotype analysis in responders (defined as a 50% reduction of the initial Hamilton score) and nonresponders after 4 weeks of antidepressant treatment showed that the haplotype derived from the rs2227631-G and rs1799889-4G polymorphisms was lower in responders than nonresponders (11.4 vs. 22.4%, P=0.014). Conclusion Our findings show, for the first time, that SERPINE1 genetic variants may play a role in MDD susceptibility and in the acute therapeutic response to selective serotonin reuptake inhibitors.
Mental Accounting, Loss Aversion, and Individual Stock Returns

We study equilibrium firm-level stock returns in two economies: one in which investors are loss averse over the fluctuations of their stock portfolio and another in which they are loss averse over the fluctuations of individual stocks that they own. Both approaches can shed light on empirical phenomena, but we find the second approach to be more successful: in that economy, the typical individual stock return has a high mean and excess volatility, and there is a large value premium in the cross-section which can, to some extent, be captured by a commonly used multifactor model.
Na+–Ca2+ exchange and its implications for calcium homeostasis in primary cultured rat brain microvascular endothelial cells

1 The role of Na+–Ca2+ exchange in the regulation of the cytosolic free Ca2+ concentration ([Ca2+]i) was studied in primary cultured rat brain capillary endothelial cells. [Ca2+]i was measured by digital fluorescence imaging in cells loaded with fura‐2. 2 ATP (100 μm) applied for a short period of time (6 s) caused a rise in [Ca2+]i from 127 ± 3 (n= 290) to 797 ± 25 nm, which then declined to the resting level, with a t½time required for [Ca2+]i to decline to half of peak [Ca2+]i) of 5.4 ± 0.09 s. This effect was independent of external Ca2+ and could be abolished by previously discharging the Ca2+ pool of the endoplasmic reticulum with thapsigargin (1 μm). 3 Application of thapsigargin (1 μm) or cyclopiazonic acid (10 μm) to inhibit the Ca2+‐ATPase of the endoplasmic reticulum 6 s prior to ATP application did not influence the peak [Ca2+]i but greatly reduced the rate of decline of [Ca2+]i, with t½ values of 15 ± 1.6 and 23 ± 3 s, respectively. 4 In the absence of external Na+ (Na+ replaced by Li+ or N‐methylglucamine) the basal [Ca2+]i was slightly elevated (152 ± 6 nm) and the restoration of [Ca2+]i after the ATP stimulation was significantly slower (t½, 7.3 ± 0.46 s in Li+ medium, 8.12 ± 0.4 s in N‐methylglucamine medium). 5 The external Na+‐dependent component of the [Ca2+]i sequestration was also demonstrated in cells stimulated by ATP subsequent to addition of cyclopiazonic acid; in a Na+‐free medium [Ca2+]i remained at the peak level in 88% of the cells after stimulation with ATP. 6 Addition of monensin (10 μm) in the presence of external Na+ increased the resting [Ca2+]i to 222 ± 9 nm over ∼1 min and subsequent removal of extracellular sodium resulted in a further increase in [Ca2+]i to a peak of 328 ± 11 nm, which was entirely dependent on external Ca2+. 7 These findings indicate that a functional Na+–Ca2+ exchanger is present at the blood‐brain barrier, which plays a significant role in shaping the stimulation‐evoked [Ca2+]i signal and is able to work in reverse mode under pharmacological conditions.
Hypoxia and Photofrin Uptake in the Intraperitoneal Carcinomatosis and Sarcomatosis of Photodynamic Therapy Patients

Purpose: Response to photodynamic therapy depends on adequate tumor oxygenation as well as sufficient accumulation of photosensitizer in the tumor. The goal of this study was to investigate the presence of hypoxia and retention of the photosensitizer Photofrin in the tumors of patients with intra-abdominal carcinomatosis or sarcomatosis. Experimental Design: Tumor nodules from 10 patients were studied. In nine of these patients, hypoxia was identified in histological sections of biopsied tumor after administration of the hypoxia marker 2-(2-nitroimidazol-1[H]-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide (EF5). In separate tumor nodules from 10 patients, Photofrin uptake was measured by fluorescence after tissue solubilization. Results: Hypoxia existed in the tumors of five patients, with three of these patients demonstrating at least one severely hypoxic nodule. Physiological levels of oxygen were present in the tumors of four patients. An association between tumor size and hypoxia was not evident because some tumor nodules as small as ∼2 mm in diameter were severely hypoxic. However, even these tumor nodules contained vascular networks. Three patients with severely hypoxic tumor nodules exhibited moderate levels of Photofrin uptake of 3.9 ± 0.4 to 3.9 ± 0.5 ng/mg (mean ± SE). The four patients with tumors of physiological oxygenation did not consistently exhibit high tumor concentrations of Photofrin: mean ± SE drug uptake among these patients ranged from 0.6 ± 0.8 to 5.8 ± 0.5 ng/mg. Conclusions: Carcinomatosis or sarcomatosis of the i.p. cavity may exhibit severe tumor hypoxia. Photofrin accumulation in tumors varied by a factor of ∼10× among all patients, and, on average, those with severe hypoxia in at least one nodule did not demonstrate poor Photofrin uptake in separate tumor samples. These data emphasize the need for reconsideration of the generally accepted paradigm of small tumor size, good oxygenation, and good drug delivery because this may vary on an individual tumor basis.
Long‐term development of phosphorus and nitrogen loads through the subsurface and surface water systems of drainage basins

We analyze and compare simulations and controlling processes of the past 60 years and possible future short‐ and long‐term development of phosphorus and nitrogen loading from the Swedish Norrström drainage basin to the Baltic Sea under different inland source management scenarios. Results indicate that both point and agricultural source inputs may need to be decreased by at least 40% in order to reach a long‐term sustainable 30% reduction of anthropogenic coastal nitrogen loading, as required by national environmental goals. A corresponding 20% anthropogenic phosphorus load reduction goal may be reached in the short term by analogous combined 40% source input reduction, but appears impossible to maintain as a long‐term achievement by inland source abatement only. In general, realistic quantification of the slow subsurface nutrient transport and accumulation‐release dynamics may be essential for accurately predicting and managing nutrient loading to surface and coastal waters.
Clostridium difficile-associated diarrhoea: bovine anti-Clostridium difficile whey protein to help aid the prevention of relapses

Antibiotic treatment can usually help in symptomatic recovery in Clostridium difficile -associated diarrhoea (CDAD), but recurrent episodes of diarrhoea remain a major problem.1–4 Besides increasing the dose or extending the course of antibiotics, and using alternating or pulsed regimens, there are no effective alternatives to prevent relapses.5 Previously, we reported on anti- Clostridium difficile whey protein concentrate (anti-CD-WPC) made from the milk of cows immunised against C difficile and its toxins. Anti-CD-WPC is prepared using standard techniques used in the milk industry, and contains a high concentration of sIgA directed against C difficile and its toxins. It neutralises the cytotoxicity of C difficile toxins in vitro and protects hamsters against otherwise lethal C difficile -associated cecitis.6 The aim of this study was to assess the preliminary efficacy of anti-CD-WPC in aiding the prevention of relapses in patients with CDAD confirmed by positive faecal C difficile toxin assay and …
GemDroid: a framework to evaluate mobile platforms

As the demand for feature-rich mobile systems such as smartphones and tablets has outpaced other computing systems and is expected to continue at a faster rate, it is projected that SoCs with tens of cores and hundreds of IPs (or accelerator) will be designed to provide unprecedented level of features and functionality in future. Design of such mobile systems with required QoS and power budgets along with other design constraints will be a daunting task for computer architects since any ad hoc, piece-meal solution is unlikely to result in an optimal design. This requires early exploration of the complete design space to understand the system-level design trade-offs. To the best of our knowledge, there is no such publicly available tool to conduct a holistic evaluation of mobile platforms consisting of cores, IPs and system software. This paper presents GemDroid, a comprehensive simulation infrastructure to address these concerns. GemDroid has been designed by integrating the Android open-source emulator for facilitating execution of mobile applications, the GEM5 core simulator for analyzing the CPU and memory centric designs, and models for several IPs to collectively study their impact on system-level performance and power. Analyzing a spectrum of applications with GemDroid, we observed that the memory subsystem is a vital cog in the mobile platform because, it needs to handle both core and IP traffic, which have very different characteristics. Consequently, we present a heterogeneous memory controller (HMC) design, where we divide the memory physically into two address regions, where the first region with one memory controller (MC) handles core-specific application data and the second region with another MC handles all IP related data. The proposed modifications to the memory controller design results in an average 25% reduction in execution time for CPU bound applications, up to 11% reduction in frame drops, and on average 17% reduction in CPU busy time for on-screen (IP bound) applications.
On‐chip spectroscopic assessment of microbial susceptibility to antibiotics within 3.5 hours

In times of rising antibiotic resistances, there is a high need for fast, sensitive and specific methods to determine antibiotic susceptibilities of bacterial pathogens. Here, we present an integrated microfluidic device in which bacteria from diluted suspensions are captured in well‐defined regions using on‐chip dielectrophoresis and further analyzed in a label‐free and non‐destructive manner using Raman spectroscopy. Minimal sample preparation and automated sample processing ensure safe handling of infectious material with minimal hands‐on time for the operator. Clinical applicability of the presented device is demonstrated by antibiotic susceptibility testing of Escherichia coli towards the commonly prescribed second generation fluoroquinolone ciprofloxacin. Ciprofloxacin resistant E. coli were differentiated from sensitive E. coli with high accuracy within roughly three hours total analysis time paving the way for future point‐of‐care devices. Spectral changes leading to the discrimination between sensitive and resistant bacteria are in excellent agreement with expected metabolic changes in the bacteria due to the mode of action of the drug. The robustness of the method was confirmed with experiments involving different chip devices with different designs, both electrode as well as microfluidics design, and material. Furthermore, general applicability was demonstrated with different operators over an extended time period of half a year.
Comparing clusterings: an axiomatic view

This paper views clusterings as elements of a lattice. Distances between clusterings are analyzed in their relationship to the lattice. From this vantage point, we first give an axiomatic characterization of some criteria for comparing clusterings, including the variation of information and the unadjusted Rand index. Then we study other distances between partitions w.r. t these axioms and prove an impossibility result: there is no "sensible" criterion for comparing clusterings that is simultaneously (1) aligned with the lattice of partitions, (2) convexely additive, and (3) bounded.
Human papillomavirus testing in primary cervical screening and the cut-off level for hybrid capture 2 tests: systematic review

Objective To determine the trade-off between the sensitivity and the specificity for high grade cervical intraepithelial neoplasia at hybrid capture 2 cut-off values above the standard ≥1 relative light units/cut-off level (rlu/co). Design Systematic review. Data sources PubMed. Study selection Randomised controlled trials in primary cervical screening using hybrid capture 2 testing in the intervention arms. Articles published until August 2010 were included if the numbers of women with positive test results and with cervical intraepithelial neoplasia were stratified by hybrid capture 2 cut-off levels. Participants Women in the baseline screening rounds of the trials. Interventions Hybrid capture 2 screening in the baseline round including the diagnostic follow-up as practised in the randomised controlled trials and as reported by hybrid capture 2 cut-off values. Results Owing to heterogeneity in the trials, meta-analysis was not possible. Including cut-off values up to ≥10 rlu/co, 25 observation points were available for analysis. The relative sensitivity for cervical intraepithelial neoplasia grade III or higher at cut-off levels of ≥2, ≥4 or ≥5, and ≥10 rlu/co compared with a cut-off level of ≥1 rlu/co varied by trial, but at their lowest they were 0.97, 0.92, and 0.91, respectively. A similar pattern was observed for cervical intraepithelial neoplasia grade II or higher. The specificity would increase by at least 1%, 2%, and 3%, respectively, so that up to 24%, 39%, and 53%, of positive hybrid capture 2 test results not associated with high grade neoplasia could be avoided. Only two outliers existed to this general pattern. Conclusions Although the data were derived from the baseline screening rounds only, the decrease in the sensitivity for high grade cervical intraepithelial neoplasia using a hybrid capture 2 cut-off level between ≥2 rlu/co and ≥10 rlu/co seemed acceptable given the international recommendations for testing for human papillomavirus DNA in cervical screening, which require 90% or more sensitivity for cervical intraepithelial neoplasia grade II or higher compared with hybrid capture 2 at ≥1 rlu/co. The data suggest that the hybrid capture 2 cut-off level could be increased in primary screening; this seems reasonably safe and is significantly less burdensome for women.
Analysis of the disaster characteristics and emergency response of the Jiuzhaigou earthquake

Abstract. China's earthquake emergency response system has been improved by lessons learned from multiple earthquakes. This paper focuses on the Ms 7.0 earthquake that occurred in Jiuzhaigou County, Sichuan Province, China, on 8 August 2017 and assesses the emergency response activities of all levels of government as well as various departments, rescue teams, enterprises and public institutions and social organizations. The emergency response is compared to other large earthquakes that occurred in China in recent years. The lessons learned from these experiences can inform the emergency response to future disasters. The characteristics of the Jiuzhaigou earthquake and the emergency responses after the event are analysed. The response level and resource mobilization were appropriately adjusted as the disaster developed, and various departments worked together to conduct multi-sector joint rescue efforts. Additionally, professional rescue forces and participating social organizations were more rationally mobilized than during past earthquake emergency responses. A set of effective disaster relief command and coordination mechanisms was established to facilitate cooperation between multiple departments and social organizations under the leadership of the local government. Finally, new and more effective technologies played an important role in the emergency response and rescue efforts following the earthquake.
Socialization Related Learning among New Staff in Malaysian Secondary Schools

Organizational culture is closely related to the socialization process that occurs in organizations. The purpose of this study is to investigate the socialization related learning process among new staff in secondary schools in Peninsular Malaysia. Respondents consist of new school staff categorized as graduate teachers, non-graduate teachers and support staff. The questionnaire was used to investigate the level of learning related to the socialization process among school staff. Four major elements of the socialization related learning are discussed. They include job knowledge, acculturation towards the job and organization, establishing relationship and socialization related learning satisfaction. The finding of this study shows that the level of each element of socialization related learning among the staff was moderate, mean score between 3.3 4.01. The one-way ANOVA and t-test that were used to investigate the difference among the four elements in terms of job categories, past experiences, current experience, gender, type of schools and location shows significant differences for most of the elements. The study concluded that the level of socialization related learning among new staff is satisfactory. The study implicated that the level needs to be improved especially for staff from the non-graduate and supporting group which recorded a mean lower mean.