Miracle-dz/UniFAR-FTUs huggingface dataset:
The Immunosuppressant Rapamycin Mimics a Starvation-Like Signal Distinct from Amino Acid and Glucose Deprivation

ABSTRACT RAFT1/FRAP/mTOR is a key regulator of cell growth and division and the mammalian target of rapamycin, an immunosuppressive and anticancer drug. Rapamycin deprivation and nutrient deprivation have similar effects on the activity of S6 kinase 1 (S6K1) and 4E-BP1, two downstream effectors of RAFT1, but the relationship between nutrient- and rapamycin-sensitive pathways is unknown. Using transcriptional profiling, we show that, in human BJAB B-lymphoma cells and murine CTLL-2 T lymphocytes, rapamycin treatment affects the expression of many genes involved in nutrient and protein metabolism. The rapamycin-induced transcriptional profile is distinct from those induced by glucose, glutamine, or leucine deprivation but is most similar to that induced by amino acid deprivation. In particular, rapamycin treatment and amino acid deprivation up-regulate genes involved in nutrient catabolism and energy production and down-regulate genes participating in lipid and nucleotide synthesis and in protein synthesis, turnover, and folding. Surprisingly, however, rapamycin had effects opposite from those of amino acid starvation on the expression of a large group of genes involved in the synthesis, transport, and use of amino acids. Supported by measurements of nutrient use, the data suggest that RAFT1 is an energy and nutrient sensor and that rapamycin mimics a signal generated by the starvation of amino acids but that the signal is unlikely to be the absence of amino acids themselves. These observations underscore the importance of metabolism in controlling lymphocyte proliferation and offer a novel explanation for immunosuppression by rapamycin.
Dexmedetomidine vs. propofol for short-term sedation of postoperative mechanically ventilated patients.

BACKGROUND Propofol is often used for sedation in the intensive care unit. The aim of this study was to compare the efficacy and endocrine response of propofol vs. the new alpha2-agonist dexmedetomidine for sedation in surgical intensive care patients who need postoperative short-term ventilation. METHODS Our work is a randomized clinical study conducted on sixty adult patients who required postoperative short term ventilation and sedation. The patients were allocated randomly, to receive IV infusion of either dexmedetomidine 0.2-0.5 microg/kg/h or propofol 0.5-1 mg/kg/h. Hemodynamic parameters, Ramsay sedation score, extubation time and serum cortisol and interleukin-6 (IL-6) levels were measured. RESULTS Ramsay sedation score was 4.1+/-1 and 4+/-0.9 for propofol and dexmedetomidine, respectively, (p=0.59.) Total fentanyl dose in the propofol group was 75+/-15 microg compared to 15+/-10.5 microg in the dexmedetomidine group, (p=0.0045). Patients who received dexmedetomidine infusion had significantly lower heart rates compared to patients who received propofol infusion, (p=0.041). Pre-infusion serum concentrations of IL-6 were comparable in both groups, while the 24 h post-infusion levels were insignificantly decreased in both groups compared to pre-infusion level, (p=0.36). There were no intergroup differences in serum cortisol concentrations (p=0.231). CONCLUSIONS Dexmedetomidine and propofol are safe sedative drugs for postoperative mechanichally ventilated patients. Patients were easily aroused to co-operate without showing signs of irritations with less fentanyl analgesia in the dexmedetomidine group. Dexmedetomidine and propofol do not inhibit adrenal function, but they may influence the inflammatory response.
Degradation of nitrobenzene in simulated wastewater by iron-carbon micro-electrolysis packing

The reductive degradation of nitrobenzene (NB) by iron-carbon micro-electrolysis packing was investigated. The influence of initial NB concentration, pH value and packing amount on the removal rate of NB were studied. The results showed that the reaction with packing followed the pseudo-first-order reaction. The optimum pH was 3.0 for the degradation of NB in the tested pH ranges of 3–9 and the optimum packing amount was 40 g/200 ml. The flow-through column packed with packing was designed to remove NB from simulated wastewater for approximately 68 days. The removal rate was over 90% within initial periods. It could be seen that after running for 68 days, the packing still had good performance after the long-term column experiment. In addition, the changes of the packing surfaces morphologies and matters before, during and after the column experiment were analysed by scanning electron microscopy in conjunction with energy-dispersion spectroscopy (EDS).
A Multi-Agent Framework for Personalized Information Filtering

As today the amount of accessible information is overwhelming, the intelligent and personalized filtering of available information is a great challenge. The main problems are that the relevant information is spread over a big number of sources and useful information is hidden under the huge amount of useless data. To cope with this problem several filtering and information query strategies have been developed but they are usually specialized on a bounded problem and do not take into account the individual preferences of the user. Moreover most search engines rate every document separately and do consider the relationship between the documents in the result set. In this paper we present a multi-agent system that integrates heterogeneous information sources, a big number of filtering and rating strategies as well as strategies for combining ratings from different agents and optimizing the filter result set according to the individual user preferences. In the framework each information source, filtering strategy and optimization strategy is presented as an intelligent agent so that the system is open and extendable at runtime. The framework monitors the resource demand of each agent as well as the availability of system resources for choosing the most adequate agents according to the requested response time. User feedback is collected and used for optimizing the filtering strategies and for learning in which context which strategy performs best. The filtering framework provides the basis for the Personalized Information System. The first evaluation results show that the filtering framework provides better results and that new filtering strategies can be seamlessly integrated.
Role of Endogenous Angiotensin II on Glutamatergic Actions in the Rostral Ventrolateral Medulla in Goldblatt Hypertensive Rats

Abstract—In this study, we investigated the cardiovascular responses mediated by rostral ventrolateral medulla neurons (RVLM) in the Goldblatt hypertension model (2K-1C) treated or not treated with captopril. The actions of glutamate into the RVLM were tested, injecting glutamate (0.1 mol/L, 100 nL) and its antagonist kynurenic acid (0.02 mol/L, 100 nL). Glycine (0.5 mol/L, 100 nL) was also microinjected. Experiments were performed in male Wistar rats (weight, 250 to 300 g); 5 groups were studied: (1) 2K-1C nontreated (H, n=6); (2) 2K-1C treated with captopril, 10 mg/kg per day (Ht10, n=10); (3) 2K-1C treated with captopril, 50 mg/kg per day (Ht50, n=7); (4) control normotensive rats (N, n=7); and (5) normotensive rats treated with captopril, 50 mg/kg per day (Nt50, n=8). All experiments in 2K-1C were performed 6 weeks after renal surgery; captopril treatment lasted for the last 2 weeks. In urethane-anesthetized rats (1.2 g/kg IV), bilateral microinjection of glycine into the RVLM caused a depressor response; there was no difference between groups in relation to the change of variation (N: 54±2; H: 46±12; Ht10: 50±3, and Ht50: 42±7 mm Hg). Only in the H group, kynurenic acid microinjection into the RVLM caused a depressor response (H: 158±8 to 132±8 mm Hg). Glutamate response was larger in hypertensive than in normotensive rats (N: 38±2.6 and H: 55±6); no difference was observed between hypertensive groups. The data suggest that glutamate acts tonically to drive the RVLM in 2K-1C rats, and this action is modulated by endogenous angiotensin II. The increase in the glutamate actions within the RVLM may contribute to the pathogenesis of renovascular hypertension.
Randomized Controlled Trial of Aerobic Exercise on Insulin and Insulin-like Growth Factors in Breast Cancer Survivors: The Yale Exercise and Survivorship Study

Background: High insulin and insulin-like growth factor-I (IGF-I) levels may be associated with an increased breast cancer risk and/or death. Given the need to identify modifiable factors that decrease insulin, IGF-I, and breast cancer risk and death, we investigated the effects of a 6-month randomized controlled aerobic exercise intervention versus usual care on fasting insulin, IGF-I, and its binding protein (IGFBP-3) in postmenopausal breast cancer survivors. Methods: Seventy-five postmenopausal breast cancer survivors were identified from the Yale-New Haven Hospital Tumor Registry and randomly assigned to an exercise (n = 37) or usual care (n = 38) group. The exercise group participated in 150 minutes per week of moderate-intensity aerobic exercise. The usual care group was instructed to maintain their current physical activity level. A fasting blood sample was collected on each study participant at baseline and 6 months. Blood levels of insulin and IGF were measured with ELISA. Results: On average, exercisers increased aerobic exercise by 129 minutes per week compared with 45 minutes per week among usual care participants (P < 0.001). Women randomized to exercise experienced decreases in insulin, IGF-I, and IGFBP-3, whereas women randomized to usual care had increases in these hormones. Between-group differences in insulin, IGF-I, and IGFBP-3 were 20.7% (P = 0.089), 8.9% (P = 0.026), and 7.9% (P = 0.006), respectively. Conclusions: Moderate-intensity aerobic exercise, such as brisk walking, decreases IGF-I and IGFBP-3. The exercise-induced decreases in IGF may mediate the observed association between higher levels of physical activity and improved survival in women diagnosed with breast cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(1):306–13)
Rhodopsin Signaling and Organization in Heterozygote Rhodopsin Knockout Mice*

Rhodopsin (Rho) resides within internal membrane structures called disc membranes that are found in the rod outer segments (ROS) of photoreceptors in the retina. Rho expression is essential for formation of ROS, which are absent in knockout Rho-/- mice. ROS of mice heterozygous for the Rho gene deletion (Rho+/-) may have a lower Rho density than wild type (WT) membranes, or the ROS structure may be reduced in size due to lower Rho expression. Here, we present evidence that the smaller volume of ROS from heterozygous mice is most likely responsible for observed electrophysiological response differences. In Rho+/- mice as compared with age-matched WT mice, the length of ROS was shorter by 30–40%, and the average diameter of ROS was reduced by ∼20%, as demonstrated by transmission and scanning electron microscopy. Together, the reduction of the volume of ROS was ∼60% in Rho+/- mice. Rho content in the eyes was reduced by ∼43% and 11-cis-retinal content in the eye was reduced by ∼38%, as determined by UV-visible spectroscopy and retinoid analysis, respectively. Transmission electron microscopy of negatively stained disc membranes from Rho+/- mice indicated a typical morphology apart from the reduced size of disc diameter. Power spectra calculated from disc membrane regions on such electron micrographs displayed a diffuse ring at ∼4.5 nm-1, indicating paracrystallinity of Rho. Atomic force microscopy of WT and Rho+/- disc membranes revealed, in both cases, Rho organized in paracrystalline and raftlike structures. From these data, we conclude that the differences in physiological responses measured in WT and Rho+/- mice are due to structural changes of the whole ROS and not due to a lower density of Rho.
A Critique of Planning Models for Postsecondary Education Current Feasibility, Potential Relevance, and a Prospectus for Further Research*

This paper reviews recent research and policy analysis in the area of postsecondary education, concluding that (1) the biases inherent in the prevailing system of research support encourage analytical excesses which obfuscate the inadequacy of existing knowledge; (2) the major historicalforces impinging on the postsecondary education system will create fundamental strains, resulting in a dramatic recasting of important policy issues; (3) in light of these forces and of the knowledge required to deal with the realities of the emerging future, previous research is of very limited relevance; and (4) if previous research is of limited usefulness, then large-scale sectoral models (specifically, the NCHEMS Federal Planning Model and the NCFPE Postsecondary Education Financing Model) which purport to integrate existing knowledge into a coherent characterization of the larger system at best provide only the appearance of rationality to policy action.
Loss-Scaled Large-Margin Gaussian Mixture Models for Speech Emotion Classification

This paper considers a learning framework for speech emotion classification using a discriminant function based on Gaussian mixture models (GMMs). The GMM parameter set is estimated by margin scaling with a loss function to reduce the risk of predicting emotions with high loss. Here, the loss function is defined as a function of a distance metric using the Watson and Tellegen's emotion model. Margin scaling is known to have good generalization ability and can be considered appropriate for emotion modeling where the parameter set is likely to be over-fitted to the training data set whose characteristics may differ from those of the testing data set. Our learning framework is formulated as a constrained optimization problem which is solved using semi-definite programming. Three tasks were evaluated: acted emotion classification, natural emotion classification, and cross database emotion classification. In each task, four loss functions were evaluated. In all experiments, results consistently show that margin scaling improves the classification accuracy over other learning frameworks based on the maximum-likelihood, maximum mutual information and max-margin framework without margin scaling. Experiment results also show that margin scaling substantially reduces the overall loss compared to the max-margin framework without margin scaling.
Verifying computations with state ( extended version )

When a client outsources a job to a third party (e.g., the cloud), how can the client check the result, without reexecuting the computation? Recent work in proof-based verifiable computation has made significant progress on this problem by incorporating deep results from complexity theory and cryptography into built systems. However, these systems work within a stateless model: they exclude computations that interact with RAM or a disk, or for which the client does not have the full input. This paper describes Pantry, a built system that overcomes these limitations. Pantry composes proofbased verifiable computation with untrusted storage: the client expresses its computation in terms of digests that attest to state, and verifiably outsources that computation. Using Pantry, we extend verifiability to MapReduce jobs, simple database queries, and interactions with private state. Thus, Pantry takes another step toward practical proof-based verifiable computation for realistic applications.
When learning is just a click away: Does simple user interaction foster deeper understanding of multimedia messages?

In 2 experiments, students received 2 presentations of a narrated animation that explained how lightning forms followed by retention and transfer tests. In Experiment 1, learners who were allowed to exercise control over the pace of the narrated animation before a second presentation of the same material at normal speed (part-whole presentation) performed better on transfer but not retention tests compared with learners who received the same 2 presentations in the reverse order (whole-part presentation). In Experiment 2, learners who were allowed to exercise control over the pace of the narrated animation across 2 presentations (part-part presentation) performed better on transfer but not retention tests compared with learners who received the same 2 presentations at normal speed without any learner control (whole-whole presentation). These results are consistent with cognitive load theory and a 2-stage theory of mental model construction.
Comments on Housing Price Booms and the Current Account ∗

Adam et al. (2011) propose and analyze an interesting model of house price dynamics. It is pitched as an open economy model and used to study the relationship between aggregate debt and house prices. The model suggests a linkage between the current account and the value of the housing stock. The authors present some figures that motivate their analysis with the financial crisis an important component of their data summaries. Their modeling of asset valuation follows Kiyotaki and Moore (1997) by exploring the role of collateral, and follows Adam and Marcet (2011), and related unpublished work by exploring a particular way to relax an assumption of rational expectations. My comments focus primarily on a simplified version of their model, which I use to suggest ways to make this line of research more empirically ambitious. I also remark on the potential role of nonlinearities in the model specification for altering the implications.
General practitioner turnover and migration in England 1990-94.

BACKGROUND In tandem with fears about a GP workforce crisis, increasing attention is being focused on the supply and distribution of primary care services: on general practitioners in particular. Differential turnover and migration across health authority boundaries could lead to a maldistribution of GPs, yet comprehensive studies of GP turnover are non-existent. AIM To quantify general practitioner (GP) turnover and migration in England from 1990 to 1994. METHOD Yearly data from 1 October 1990 to 1 October 1994 were collected on GPs in England practising full time, including average yearly turnover, rates of entry to and exit from general practice, and net migration among GPs. All were calculated at the family health service authority (now the new health authorities) level. RESULTS Average yearly GP turnover ranges from 2.9% in Shropshire to 7.8% in Kensington, Chelsea and Westminster; turnover is associated with deprivation and high-need areas. Migration of GPs across health authority borders was rare. Entry and exit rates were also positively related to measures of deprivation and need. Relatively underprovided health authorities lost 23 GPs over the study period as a result of migration; relatively overprovided ones gained three. CONCLUSION Turnover is driven primarily by exits from general practice and is related to deprivation and high need. Retention appears to be the main problem in ensuring an adequate GP supply in relatively deprived and underprovided health authorities.
Systematic kinetic analysis of mitotic dis- and reassembly of the nuclear pore in living cells

During mitosis in higher eukaryotes, nuclear pore complexes (NPCs) disassemble in prophase and are rebuilt in anaphase and telophase. NPC formation is hypothesized to occur by the interaction of mitotically stable subcomplexes that form defined structural intermediates. To determine the sequence of events that lead to breakdown and reformation of functional NPCs during mitosis, we present here our quantitative assay based on confocal time-lapse microscopy of single dividing cells. We use this assay to systematically investigate the kinetics of dis- and reassembly for eight nucleoporin subcomplexes relative to nuclear transport in NRK cells, linking the assembly state of the NPC with its function. Our data establish that NPC assembly is an ordered stepwise process that leads to import function already in a partially assembled state. We furthermore find that nucleoporin dissociation does not occur in the reverse order from binding during assembly, which may indicate a distinct mechanism.
Breeding of New Strains of Mushroom by Basidiospore Chemical Mutagenesis

Abstract Chemical mutagenesis of basidiospores of Hypsizygus marmoreus generated new mushroom strains. The basidospores were treated with methanesulfonate methylester, an alkylating agent, to yield 400 mutant monokaryotic mycelia. Twenty fast-growing mycelia were selected and mated each other by hyphal fusion. Fifty out of the 190 matings were successful (mating rate of 26.3%), judged by the formation of clamp connections. The mutant dikaryons were cultivated to investigate their morphological and cultivation characteristics. Mutant strains No. 3 and No. 5 showed 10% and 6% increase in fruiting body production, respectively. Eight mutant strains showed delayed and reduced primordia formation, resulting in the reduced production yield with prolonged cultivation period. The number of the fruiting bodies of mutant No. 31, which displayed reduced primordial formation, was only 15, compared to the parental number of 65. Another interesting phenotype was a fruiting body with a flattened stipe and pileus. Dikaryons generated by mating with the mutant spore No. 14 produced flat fruiting bodies. Further molecular biological studies will provide details of the mechanism. This work shows that the chemical mutagenesis approach is highly utilizable in the development of mushroom strains as well as in the generation of resources for molecular genetic studies.
Is High Pulse Pressure a Marker of Preclinical Cardiovascular Disease?

This study tests the hypothesis that high brachial pulse pressure might constitute preclinical cardiovascular disease, rather than a risk factor. We studied 1250 subjects (472 nonobese normotensive [<135/80 mm Hg] and 778 untreated hypertensive). Central pulse pressure was estimated from brachial pulse pressure and age and divided by stroke volume (PP/SV). Brachial pulse pressure was considered high when >63 mm Hg, and peripheral resistance high when >90th percentile of normal distribution. Among hypertensive subjects, 34% had high resistance; among them, 33% had high brachial pulse pressure, as opposed to 147 of 516 patients (28.5%) with normal resistance (P=not significant). After adjusting for age, sex, race, body mass index, heart rate, and center, left ventricular (LV) internal dimension and mass were lower with high resistance, and higher when brachial pulse pressure was high. PP/SV was 36% higher with high resistance than with normal resistance, and higher when brachial pulse pressure was high (all P<0.0001). Factorial analysis demonstrated that associations of high brachial pulse pressure with both higher PP/SV and LV mass were independent of other pressure components. Thus, because of these associations, our hypothesis is that in hypertension, pulse pressure may be considered as a marker of preclinical cardiovascular disease, similar to LV mass and PP/SV, rather than a cardiovascular risk factor.