Miracle-dz/UniFAR-FTUs huggingface dataset:
Ventromedial Preoptic Prostaglandin E2 Activates Fever-Producing Autonomic Pathways

Fever is thought to be initiated by pyrogenic cytokines inducing the production of prostaglandin E2 (PGE2) in the preoptic area (POA); PGE2 may act as a paracrine mediator that stimulates the neural pathways that raise body temperature. This essential role for prostaglandins in fever first was proposed 25 years ago, but the specific preoptic cell groups at which PGE2 acts and the pathways through which fever is produced remain poorly understood. To better define the role of preoptic PGE2 in fever, we developed a new method for combining acute brain injections with Fos immunohistochemistry. We microinjected a threshold dose of PGE2 to construct an anatomically detailed map of fever-producing preoptic sites. The most pyrogenic preoptic sites were clustered along the ventromedial aspect of the POA, surrounding and just anterior to the organum vasculosum of the lamina terminalis. We then used Fos immunohistochemistry to identify the pattern of neural activation induced by fever-producing preoptic injections of PGE2 and compared it with the Fos pattern seen after systemic immune stimulation. PGE2 fever was accompanied by Fos induction in the ventromedial POA and the parvicellular subnuclei of the paraventricular nucleus of the hypothalamus (PVH). In contrast to the Fos pattern seen after intravenous lipopolysaccharide administration, PGE2 injection did not induce Fos in the circumventricular organs or the magnocellular subnuclei of the PVH. These observations establish a potential site of PGE2 action during fever and help define candidate pathways through which fever occurs.
Hill’s equation of muscle performance and its hidden insight on molecular mechanisms

Muscles shorten faster against light loads than they do against heavy loads. The hyperbolic equation first used by A.V. Hill over seven decades ago to illustrate the relationship between shortening velocity and load is still the predominant method used to characterize muscle performance, even though it has been regarded as purely empirical and lacking precision in predicting velocities at high and low loads. Popularity of the Hill equation has been sustained perhaps because of historical reasons, but its simplicity is certainly attractive. The descriptive nature of the equation does not diminish its role as a useful tool in our quest to understand animal locomotion and optimal design of muscle-powered devices like bicycles. In this Review, an analysis is presented to illustrate the connection between the historic Hill equation and the kinetics of myosin cross-bridge cycle based on the latest findings on myosin motor interaction with actin filaments within the structural confines of a sarcomere. In light of the new data and perspective, some previous studies of force–velocity relations of muscle are revisited to further our understanding of muscle mechanics and the underlying biochemical events, specifically how extracellular and intracellular environment, protein isoform expression, and posttranslational modification of contractile and regulatory proteins change the interaction between myosin and actin that in turn alter muscle force, shortening velocity, and the relationship between them.
A figure of merit for the analysis of spoken dialog systems

In this paper, a single metric, which we will call the figure of merit , for the quantitative analysis and comparison of spoken dialog systems is introduced. This figure of merit is the product of the weighted dialog accuracy (expressed as the rate of success) and the weighted dialog efficiency (expressed as the average number of concepts per turn). Actually, it is highly desirable to have a quick and accurate dialog. However, these two requirements are conflicting. That is, an improvement in efficiency is accomplished at the expense of accuracy or vice versa. This makes difficult to compare two different spoken dialog systems or tune a particular system. We believe that this figure of merit would avoid those difficulties. To illustrate its use, we consider spoken dialog systems with different dialog strategies and compare them by performing quantitative analysis based on the finate state models of information items using the proposed metric.
Structure of the Intermediate Filament-Binding Region of Desmoplakin

Desmoplakin (DP) is a cytoskeletal linker protein that connects the desmosomal cadherin/plakoglobin/plakophilin complex to intermediate filaments (IFs). The C-terminal region of DP (DPCT) mediates IF binding, and contains three plakin repeat domains (PRDs), termed PRD-A, PRD-B and PRD-C. Previous crystal structures of PRDs B and C revealed that each is formed by 4.5 copies of a plakin repeat (PR) and has a conserved positively charged groove on its surface. Although PRDs A and B are linked by just four amino acids, B and C are separated by a 154 residue flexible linker, which has hindered crystallographic analysis of the full DPCT. Here we present the crystal structure of a DPCT fragment spanning PRDs A and B, and elucidate the overall architecture of DPCT by small angle X-ray scattering (SAXS) analysis. The structure of PRD-A is similar to that of PRD-B, and the two domains are arranged in a quasi-linear arrangement, and separated by a 4 amino acid linker. Analysis of the B-C linker region using secondary structure prediction and the crystal structure of a homologous linker from the cytolinker periplakin suggests that the N-terminal ~100 amino acids of the linker form two PR-like motifs. SAXS analysis of DPCT indicates an elongated but non-linear shape with Rg = 51.5 Å and Dmax = 178 Å. These data provide the first structural insights into an IF binding protein containing multiple PRDs and provide a foundation for studying the molecular basis of DP-IF interactions.
Roflumilast and dyspnea in patients with moderate to very severe chronic obstructive pulmonary disease: a pooled analysis of four clinical trials

Purpose Breathlessness is a predominant symptom of chronic obstructive pulmonary disease (COPD), making it a valuable outcome in addition to lung function to assess treatment benefit. The phosphodiesterase-4 inhibitor roflumilast has been shown to provide small but significant improvements in dyspnea, as measured by the transition dyspnea index (TDI), in two 1-year studies in patients with severe to very severe COPD. Patients and methods To provide a more comprehensive assessment of the impact of roflumilast on dyspnea, post hoc analyses of four 1-year roflumilast studies (M2-111, M2-112, M2-124, and M2-125) in patients with moderate to very severe COPD were conducted. Results In this pooled analysis (N=5,595), roflumilast significantly improved TDI focal scores versus placebo at week 52 (treatment difference, 0.327; P<0.0001). Roflumilast was associated with significantly greater TDI responders and significantly fewer TDI deteriorators (≥1-unit increase or decrease from baseline, respectively) versus placebo at week 52 (P<0.01, both); these significant differences were apparent by week 8 and maintained until study end (P<0.05, all). At study end, the postbronchodilator forced expiratory volume in 1 second improvement in TDI responders was significantly greater with roflumilast versus placebo (P<0.05). Similar to the overall population, improvements in TDI focal scores at week 52 were small but consistently significant over placebo in patients with chronic bronchitis, regardless of exacerbation history, concomitant treatment with short-acting muscarinic antagonists or long-acting β2-agonists, or pretreatment with inhaled corticosteroids. Conclusion This analysis shows that patients treated with roflumilast to reduce exacerbation risk may also experience small but significant improvements in dyspnea, with accompanying improvements in lung function.
Invariance of molecular charge transport upon changes of extended molecule size and several related issues

As a sanity test for the theoretical method employed, studies on (steady-state) charge transport through molecular devices usually confine themselves to check whether the method in question satisfies the charge conservation. Another important test of the theory’s correctness is to check that the computed current does not depend on the choice of the central region (also referred to as the “extended molecule”). This work addresses this issue and demonstrates that the relevant transport and transport-related properties are indeed invariant upon changing the size of the extended molecule, when the embedded molecule can be described within a general single-particle picture (namely, a second-quantized Hamiltonian bilinear in the creation and annihilation operators). It is also demonstrates that the invariance of nonequilibrium properties is exhibited by the exact results but not by those computed approximately within ubiquitous wide- and flat-band limits (WBL and FBL, respectively). To exemplify the limitations of the latter, the phenomenon of negative differential resistance (NDR) is considered. It is shown that the exactly computed current may exhibit a substantial NDR, while the NDR effect is absent or drastically suppressed within the WBL and FBL approximations. The analysis done in conjunction with the WBLs and FBLs reveals why general studies on nonequilibrium properties require a more elaborate theoretical than studies on linear response properties (e.g., ohmic conductance and thermopower) at zero temperature. Furthermore, examples are presented that demonstrate that treating parts of electrodes adjacent to the embedded molecule and the remaining semi-infinite electrodes at different levels of theory (which is exactly what most NEGF-DFT approaches do) is a procedure that yields spurious structures in nonlinear ranges of current–voltage curves.
Induction of a Global Stress Response during the First Step of Escherichia coli Plate Growth

ABSTRACT We have investigated the first events that occur when exponentially grown cells are transferred from a liquid medium (Luria-Bertani [LB]) to a solid medium (LB agar [LBA]). We observed an initial lag phase of 180 min for the wild type MG1655 without any apparent growth. This lack of growth was independent of the bacterial physiological state (either the stationary or the exponential phase), the solid medium composition, or the number of cells on the plate, but it was dependent on the bacterial genotype. Using lacZ-reporter fusions and two-dimensional electrophoresis analysis, we observed that when cells from exponential-phase cultures were plated on LBA, several global regulons, like heat shock regulons (RpoH, RpoE, CpxAR) and oxidative-stress regulons (SoxRS, OxyR, Fur), were immediately induced. Our results indicate that in order to grow on plates, bacteria must not only adapt to new conditions but also perceive a real stress.
A New Genetic Algorithm with Elliptical Crossover for Constrained Multi-objective Optimization Problems

The crossover operator plays an important role in a genetic algorithm, which produces two or more offspring for each pair of parents. With the help of the crossover operator, the genetic algorithm can explore the search space effectively. In this paper, we propose a new crossover operator called elliptical crossover operator, which can explore the search domain effectively. A local search scheme is designed to get more precise and wider nondominated solutions. In the local search scheme, the square search scheme and uniform design methods are combined. Based on the elliptical crossover operator and the local search scheme, a novel genetic algorithm is designed for constrained multi-objective optimization problems. Simulation results on several test functions indicates the effectiveness of the designed algorithm.
Game Development for Computer Science Education

Games can be a valuable tool for enriching computer science education, since they can facilitate a number of conditions that promote learning: student motivation, active learning, adaptivity, collaboration, and simulation. Additionally, they provide the instructor the ability to collect learning metrics with relative ease. As part of 21st Annual Conference on Innovation and Technology in Computer Science Education (ITiCSE 2016), the Game Development for Computer Science Education working group convened to examine the current role games play in computer science (CS) education, including where and how they fit into CS education. Based on reviews of literature, academic research, professional practice, and a comprehensive list of games for computing education, we present this working group report. This report provides a summary of existing digital games designed to enrich computing education, an index of where these games may fit into a teaching paradigm using the ACM/IEEE Computer Science Curricula 2013 [13], and a guide to developing digital games designed to teach knowledge, skills, and attitudes related to computer science.
ESTIMATION OF TIME DEPENDENTPARAMETERS IN GENERALPARABOLIC EVOLUTION

In this paper we develop a convergence theory for estimating time dependent parameters in a general class of parabolic system. We apply this theory to several problems of interest, such as estimating transport and biodegredation parameters in a contaminant transport model and the stiiness coeecient in an Euler-Bernoulli beam equation.
Sequence design for MPG QS-CDMA systems based on heuristic combinatorial optimization

This paper deals with a quasi-synchronous code division multiple access (QS-CDMA) system with a multiple processing gain (MPG) variable data rate scheme in the uplink direction and subject to multipath fading channels. An analytic expression is obtained for the signal-to-noise plus interference ratio (SNIR) at the Rake receiver output (finger). In order to maximize the SNIR, three combinatorial optimization methods applied to sequences selection are compared. Then, sequence selection methodology for this class of system is evaluated, comparing the local search optimization results with unitary Hamming distance (1-opt LS), evolutionary programming with cloning (EP-C), and simulated annealing (SA) ones. The contribution of this work consists of considering the self-interference (SI) effect, besides the multiple access interference (MAI), in the description of the proposed objective function for sequence selection and a compared analysis of three heuristic algorithms maximizing that SNIR. Also, numeric results have demonstrated the effectiveness of the proposed method for the QS-CDMA sequences selection. Copyright © 2010 John Wiley & Sons, Ltd.
Political Communication Today

Part 1 Theories, organization, partisanship and effects: theoretical approaches radio and television the press the media overall - ownership and regulation the news and current affairs effects of the media. Part 2 Parties, politicians and the media: the role of the media in the political process - pressure groups, local government and privatization governmental manipulation selling politicians - the parties and publicity - a history to 1992, market research and opinion polls, presenting the candidates and the message, party political broadcasts, political advertising, recent trends - a reflection politicians selling themselves - political speeches, the election debate, the televizing of Parliament, the political interview, politicians and the broadcasters - a reflection. Part 3 The media, democracy and the future: the media and democracy future trends.
Recent evaluations of the peer-led approach in adolescent sexual health education: a systematic review.

CONTEXT Peer-led interventions have become a popular method of providing sexual health education to adolescents, but the efficacy of this approach and the methodological quality of recent trials have not been systematically reviewed. METHODS Electronic and hand searches were conducted to identify quasi-randomized and randomized controlled trials of peer-led adolescent sexual health education published from 1998 to 2005. Studies were eligible if they had an appropriate comparison group, provided preintervention and postintervention data, and reported all outcomes. Study results were summarized and, where appropriate, pooled; in addition, 10 aspects of studies' methodological quality were assessed. RESULTS Thirteen articles met the inclusion criteria. Pooled, adjusted results from seven trials that examined the effects of peer-led interventions on condom use at last sex found no overall benefit (odds ratio, 1.0). None of the three trials that assessed consistent condom use found a benefit. One study reported a reduced risk of chlamydia (0.2), but another found no impact on STI incidence. One study found that young women (but not young men) who received peer-led education were more likely than nonrecipients to have never had sex. Most interventions produced improvements in knowledge, attitudes and intentions. Only three studies fulfilled all 10 of the assessed quality criteria; two others met nine criteria. CONCLUSIONS Despite promising results in some trials, overall findings do not provide convincing evidence that peer-led education improves sexual outcomes among adolescents. Future trials should build on the successful trials conducted to date and should strive to fulfill existing quality criteria.
Potency and stability of C terminal truncated human epidermal growth factor

INTRODUCTION Epidermal growth factor (EGF) is normally present as EGF1–53. A variety of C terminal truncated forms have been used in preliminary trials for treating gastrointestinal injury but their relative potency and stability when used in a clinical setting are unclear. Therefore, we compared the biological activity of recombinant EGF1–53, EGF1–52, EGF1–51, and the C terminal peptides EGF44–53 and EGF49–53. METHODS Purity of forms was confirmed by mass spectrometry. Bioactivity of the different EGF forms was determined using [methyl-3H] thymidine incorporation into primary rat hepatocytes and their ability to reduce indomethacin (20 mg/kg subcutaneously)/restraint induced gastric injury in rats. Stability of EGF peptides was determined by serial sampling from a syringe driver system containing EGF/4% albumin in saline. RESULTS Biological activity assays of EGF1–53, EGF1–52, and EGF1–51 gave almost identical thymidine uptake dose-response curves (maximal responses increasing baseline uptake from 4400 (600) cpm (mean (SEM)) to about 22 000 (2000) cpm when EGF was added at 1.6 nM). EGF44–53 and EGF49–53 did not stimulate 3H thymidine uptake. Control rats had 47 (4) mm2 damage/stomach, EGF1–51, EGF1–52, and EGF1–53 at 0.16 and 0.80 nmol/kg/h each reduced gastric injury by about 50% and 80%, respectively (both doses p<0.01 compared with control but no significant difference between the different forms). EGF was stable at room temperature for seven days but biological activity decreased by 35% and 40% at two and three weeks, respectively (both p<0.01). Exposure to light did not affect bioactivity. CONCLUSION EGF1–51and EGF1–52 are as biologically active as full length EGF1–53 but the C terminal penta- and decapeptides are ineffective. Clinical trials of EGF can probably use infusion systems for at least 48 hours at room temperature and with exposure to light, without reducing biological efficacy.
Increasing incidence of cutaneous melanoma in Queensland, Australia.

BACKGROUND Queensland, Australia, had the world's highest incidence rates of invasive cutaneous melanoma in the 1970s. PURPOSE The purpose of this study was to monitor trends in melanoma incidence in Queensland. METHODS We studied two time periods in which ascertainment was comparable. RESULTS In the 7.5 years up to 1987, the incidence of invasive melanoma in Queensland increased by more than one half in women (to 42.89 per 100,000) and more than doubled in men (to 55.81 per 100,000), with the most dramatic increase seen in men over age 50 years. This higher increase in men is a reversal of the previously higher rates in women. In Queensland, cumulative risks of total cutaneous melanoma (in persons aged 0-74 years), including preinvasive melanoma, have increased to one in 14 in men and to one in 17 in women. There were large increases in age-standardized incidence rates of thin lesions (less than 0.75 mm) in both sexes but not of in situ lesions, and there were also increases in thicker lesions, especially on the backs of males. CONCLUSIONS Although increased awareness and earlier diagnosis appear to have accompanied increased incidence, increased exposure to solar UV radiation during the past 50 years appears to be the most likely explanation for the rise in incidence rates. IMPLICATIONS A better understanding is needed of the causes of melanoma and of the complex relationships between constitutional factors, ambient UV radiation, and sun-exposure behavior.
Price Indexes for Drugs: A Review of the Issues

Price indexes provide a way to summarize changes in prices of individual goods and services using an aggregate statistic. An important use of these indexes is to decompose changes in spending into price and quantity components. Price indexes have roles in many areas, including in the National Income and Product Accounts and National Health Expenditure Accounts. Health economists have also used similar decompositions to inform policy debates about which levers may be used to contain cost growth. There are three particular issues that arise when discussing price and quality change. The first is deciding which particular formula and weights is most appropriate in constructing the index. Secondly, some price changes are accompanied by changes in the quality of goods. And lastly, price indexes for medical care do not have a clear link to patients’ welfare. Therefore, this paper focuses on the measurement issues, how the indexes are constructed, and how they may be used to decompose the growth in spending into price and quantity components.
NeuroVR: An Open Source Virtual Reality Platform for Clinical Psychology and Behavioral Neurosciences

In the past decade, the use of virtual reality for clinical and research applications has become more widespread. However, the diffusion of this approach is still limited by three main issues: poor usability, lack of technical expertise among clinical professionals, and high costs. To address these challenges, we introduce NeuroVR (http://www.neurovr.org--http://www.neurotiv.org), a cost-free virtual reality platform based on open-source software, that allows non-expert users to adapt the content of a pre-designed virtual environment to meet the specific needs of the clinical or experimental setting. Using the NeuroVR Editor, the user can choose the appropriate psychological stimuli/stressors from a database of objects (both 2D and 3D) and videos, and easily place them into the virtual environment. The edited scene can then be visualized in the NeuroVR Player using either immersive or non-immersive displays. Currently, the NeuroVR library includes different virtual scenes (apartment, office, square, supermarket, park, classroom, etc.), covering two of the most studied clinical applications of VR: specific phobias and eating disorders. The NeuroVR Editor is based on Blender (http://www.blender.org), the open source, cross-platform suite of tools for 3D creation, and is available as a completely free resource. An interesting feature of the NeuroVR Editor is the possibility to add new objects to the database. This feature allows the therapist to enhance the patient's feeling of familiarity and intimacy with the virtual scene, i.e., by using photos or movies of objects/people that are part of the patient's daily life, thereby improving the efficacy of the exposure. The NeuroVR platform runs on standard personal computers with Microsoft Windows; the only requirement for the hardware is related to the graphics card, which must support OpenGL.