Miracle-dz/UniFAR-FTUs huggingface dataset:
Cell-Based Small-Molecule Compound Screen Identifies Fenretinide as Potential Therapeutic for Translocation-Positive Rhabdomyosarcoma

A subset of paediatric sarcomas are characterized by chromosomal translocations encoding specific oncogenic transcription factors. Such fusion proteins represent tumor specific therapeutic targets although so far it has not been possible to directly inhibit their activity by small-molecule compounds. In this study, we hypothesized that screening a small-molecule library might identify already existing drugs that are able to modulate the transcriptional activity of PAX3/FOXO1, the fusion protein specifically found in the pediatric tumor alveolar rhabdomyosarcoma (aRMS). Towards this end, we established a reporter cell line based on the well characterized PAX3/FOXO1 target gene AP2ß. A library enriched in mostly FDA approved drugs was screened using specific luciferase activity as read-out and normalized for cell viability. The most effective inhibitor identified from this screen was Fenretinide. Treatment with this compound resulted in down-regulation of PAX3/FOXO1 mRNA and protein levels as well as in reduced expression of several of its direct target genes, but not of wild-type FOXO1, in a dose- and time-dependent manner. Moreover, fenretinide induced reactive oxygen species and apoptosis as shown by caspase 9 and PARP cleavage and upregulated miR-9. Importantly, it demonstrated a significant anti-tumor effect in vivo. These results are similar to earlier reports for two other pediatric tumors, namely neuroblastoma and Ewing sarcoma, where fenretinide is under clinical development. Our results suggest that fenretinide might represent a novel treatment option also for translocation-positive rhabdomyosarcoma.
Xanthenedione Derivatives, New Promising Antioxidant and Acetylcholinesterase Inhibitor Agents

Natural and synthetic xanthone derivatives are well-known for their ability to act as antioxidants and/or enzyme inhibitors. This paper aims to present a successful synthetic methodology towards xanthenedione derivatives and the study of their aromatization to xanthones. Additionally their ability to reduce Fe(III), to scavenge DPPH radicals and to inhibit AChE was evaluated. The results demonstrated that xanthenedione derivative 5e, bearing a catechol unit, showed higher reduction capacity than BHT and similar to quercetin, strong DPPH scavenging activity (EC50 = 3.79 ± 0.06 µM) and it was also showed to be a potent AChEI (IC50 = 31.0 ± 0.09 µM) when compared to galantamine (IC50 = 211.8 ± 9.5 µM).
Human longevity is associated with regular sleep patterns, maintenance of slow wave sleep, and favorable lipid profile

Some individuals are able to successfully reach very old ages, reflecting higher adaptation against age-associated effects. Sleep is one of the processes deeply affected by aging; however few studies evaluating sleep in long-lived individuals (aged over 85) have been reported to date. The aim of this study was to characterize the sleep patterns and biochemical profile of oldest old individuals (N = 10, age 85–105 years old) and compare them to young adults (N = 15, age 20–30 years old) and older adults (N = 13, age 60–70 years old). All subjects underwent full-night polysomnography, 1-week of actigraphic recording and peripheral blood collection. Sleep electroencephalogram spectral analysis was also performed. The oldest old individuals showed lower sleep efficiency and REM sleep when compared to the older adults, while stage N3 percentage and delta power were similar across the groups. Oldest old individuals maintained strictly regular sleep-wake schedules and also presented higher HDL-cholesterol and lower triglyceride levels than older adults. The present study revealed novel data regarding specific sleep patterns and maintenance of slow wave sleep in the oldest old group. Taken together with the favorable lipid profile, these results contribute with evidence to the importance of sleep and lipid metabolism regulation in the maintenance of longevity in humans.
Time Delay to Treatment and Mortality in Primary Angioplasty for Acute Myocardial Infarction: Every Minute of Delay Counts

Background—Although the relationship between mortality and time delay to treatment has been demonstrated in patients with acute ST-segment elevation myocardial infarction (STEMI) treated by thrombolysis, the impact of time delay on prognosis in patients undergoing primary angioplasty has yet to be clarified. The aim of this report was to address the relationship between time to treatment and mortality as a continuous function and to estimate the risk of mortality for each 30-minute delay. Methods and Results—The study population consisted of 1791 patients with STEMI treated by primary angioplasty. The relationship between ischemic time and 1-year mortality was assessed as a continuous function and plotted with a quadratic regression model. The Cox proportional hazards regression model was used to calculate relative risks (for each 30 minutes of delay), adjusted for baseline characteristics related to ischemic time. Variables related to time to treatment were age >70 years (P <0.0001), female gender (P =0.004), presence of diabetes mellitus (P =0.002), and previous revascularization (P =0.035). Patients with successful reperfusion had a significantly shorter ischemic time (P =0.006). A total of 103 patients (5.8%) had died at 1-year follow-up. After adjustment for age, gender, diabetes, and previous revascularization, each 30 minutes of delay was associated with a relative risk for 1-year mortality of 1.075 (95% CI 1.008 to 1.15; P =0.041). Conclusions—These results suggest that every minute of delay in primary angioplasty for STEMI affects 1-year mortality, even after adjustment for baseline characteristics. Therefore, all efforts should be made to shorten the total ischemic time, not only for thrombolytic therapy but also for primary angioplasty.
Neural responses to velocity gradients in macaque cortical area MT

Abstract Visual motion, i.e. the pattern of changes on the retinae caused by the motion of objects or the observer through the environment, contains important cues for the accurate perception of the three-dimensional layout of the visual scene. In this study, we investigate if neurons in the visual system, specifically in area MT of the macaque monkey, are able to differentiate between various velocity gradients. Our stimuli were random dot patterns designed to eliminate stimulus variables other than the orientation of a velocity gradient. We develop a stimulus space (“deformation space”) that allows us to easily parameterize our stimuli. We demonstrate that a substantial proportion of MT cells show tuned responses to our various velocity gradients, often exceeding the response evoked by an optimized flat velocity profile. This suggests that MT cells are able to represent complex aspects of the visual environment and that their properties make them well suited as building blocks for the complex receptive-field properties encountered in higher areas, such as area MST to which many cells in area MT project.
Batteries and Supercapacitors for Electric Vehicles

Due to increasing gas prices and environmental concerns, battery propelled electric vehicles (BEVs) and hybrid electric vehicles (HEVs) have recently drawn more attention. In BEV and HEV configurations, the rechargeable energy storage system (RESS) is a key design issue [1– 3]. Thus, the system should be able to have good performances in terms of energy density and power capabilities during acceleration and braking phases. However, the thermal stabil‐ ity, charge capabilities, life cycle and cost can be considered also as essential assessment pa‐ rameters for RESS systems.
Design and Usability of Interactive User Profiles for Online Health Communities

Online health communities provide a rich source of expertise from experienced patients, but uncovering “peer mentors” with shared circumstances is like finding a needle in a haystack—a problem that will escalate as these communities grow and diversify. We investigated interactive health interest profiles (HIPs) that summarize health-related terms extracted from users’ community posts. Through iterative design, we explored practical designs that accommodate differences in users’ community participation in three HIP prototypes: Text, Word Cloud, and Timeline. By comparing prototype usability with patients and design experts, we found that patients accurately used each prototype but completed some tasks faster with the Timeline HIP. Despite this advantage, patients preferred the Text HIP. Design experts and patients agreed that simple data overviews and granular details with salient cues that invite interactivity are key design considerations for HIPs. Findings offer key design considerations for HIPs that patients find most useful when forging critical connections.
Retiming with interconnect and gate delay

In this paper, we study the problem of retiming of sequential circuits with both interconnect and gate delay. Most retiming algorithms have assumed ideal conditions for the non-logical portions of the data paths, which are not sufficiently accurate to be used in high performance circuits today. In our modeling, we assume that the delay of a wire is directly proportional to its length. This assumption is reasonable since the quadratic component of a wire delay is significantly smaller than its linear component when the more accurate Elmore delay model is used. A simple experiment is conducted to illustrate the validity of this assumption. We present two approaches to solve this problem, both of which have polynomial time complexity. The first one can compute the optimal clock period while the second one is an improvement over the first one in terms of practical applicability. The second approach gives solutions very close to the optimal (0.13% more than the optimal on average) but in a much shorter runtime. A circuit with more than 22 K gates and 32 K wires can be optimally retimed in 83.56 seconds by a PC with an l.8 GHz Intel Xeon processor.
Delay improved Media Access Control for Passive Optical Networks

Passive Optical Networks (PONs) are a promising technology for replacing today's access networks and to combine them with metropolitan area networks, because they offer high bandwidth and cover wide distances. However, the large distances between the endpoints introduce the problem of a relatively large propagation delay. Traditional Media Access Control (MAC) protocols applied in today's PONs are not able to handle these propagation delays efficiently. We present a new MAC mechanism specifically tailored for operation in Orthogonal Frequency Division Multiplexing (OFDM) based long-reach PONs. Our approach combines classical polling and random access to join the benefits of both MAC principles to reduce transmission delays. We perform an analytical evaluation of the combined MAC mechanism as well as simulation studies. The simulation studies show that the new MAC approach is able to reduce the minimal transmission delay by up to 63%.
Generation of a conditional null allele for Cftr in mice

The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes a cAMP‐regulated chloride channel that is important in controlling the exchange of fluid and electrolytes across epithelial cells. Mutation of CFTR can lead to cystic fibrosis (CF), the most common lethal genetic disease in Caucasians. CF is a systemic illness with multiple organ systems affected including pulmonary, gastrointestinal, pancreatic, immune, endocrine, and reproductive systems. To understand the role of CFTR in the various tissues in which it is expressed, we generated a murine conditional null allele of Cftr (Cftrfl10) in which loxP sites were inserted around exon 10 of the Cftr gene. The Cftrfl10 allele was validated by generating constitutive Cftr null (CftrΔ10) mice using the protamine‐cre system. The CftrΔ10/Δ10 mice displayed almost identical phenotypes to previously published CF mouse models, including poor growth, decreased survival, intestinal obstruction, and loss of Cftr function as assessed by electrophysiology measurements on gut and nasal epithelium. Mice containing the conditional null Cftr allele will be useful in future studies to understand the role of Cftr in specific tissues and developmental time points and lead to a better understanding of CF disease. genesis 46:546–552, 2008. © 2008 Wiley‐Liss, Inc.
An Anti-Plagiarism Editor for Software Development Courses

Plagiarism is a serious issue in undergraduate computer science courses involving assessment of programming assignments. The electronic nature of these assignments means copying others' work is very easy, and the lack of variation between legitimately independent solutions makes the detection of plagiarised solutions difficult. The primary tool in combating plagiarism should be education of students about the issue. The need still exists however, for means to detect plagiarism when it does occur, and automated tools can provide valuable assistance in this task. Most such tools developed so far have focused on analysing the content of the final work submitted by students.In contrast this paper describes an anti-plagiarism approach based on consideration of the entire process of producing the submitted source-code, rather than just the source-code itself. It describes a text editor and related software which have been implemented based on the Eclipse development environment. These tools aim to discourage plagiarism by making the copying process more labour-intensive, and to aid in detection by storing data about document creation along with the document content.
The role of MyD88‐ and TRIF‐dependent signaling in monophosphoryl lipid A‐induced expansion and recruitment of innate immunocytes

Treatment with the TLR4 agonist MPLA augments innate resistance to common bacterial pathogens. However, the cellular and molecular mechanisms by which MPLA augments innate immunocyte functions are not well characterized. This study examined the importance of MyD88‐ and TRIF‐dependent signaling for leukocyte mobilization, recruitment, and activation following administration of MPLA. MPLA potently induced MyD88‐ and TRIF‐dependent signaling. A single injection of MPLA caused rapid mobilization and recruitment of neutrophils, a response that was largely mediated by the chemokines CXCL1 and ‐2 and the hemopoietic factor G‐CSF. Rapid neutrophil recruitment and chemokine production were regulated by both pathways although the MyD88‐dependent pathway showed some predominance. In further studies, multiple injections of MPLA potently induced mobilization and recruitment of neutrophils and monocytes. Neutrophil recruitment after multiple injections of MPLA was reliant on MyD88‐dependent signaling, but effective monocyte recruitment required activation of both pathways. MPLA treatment induced expansion of myeloid progenitors in bone marrow and upregulation of CD11b and shedding of L‐selectin by neutrophils, all of which were attenuated in MyD88‐ and TRIF‐deficient mice. These results show that MPLA‐induced neutrophil and monocyte recruitment, expansion of bone marrow progenitors and augmentation of neutrophil adhesion molecule expression are regulated by both the MyD88‐ and TRIF‐dependent pathways.
Knowledge, attitudes and practices regarding cervical cancer screening among village health volunteers.

BACKGROUND In the years 2014, coverage rates of cervical cancer screening in Nakornnayok province accounted to 76.5%. This was lower than the government's specified goal of 80%. Community health volunteers are members of a Thai healthcare alliance established to help promoting healthcare service communication and collaboration at the primary level. Such village health volunteers (VHVs) are established in most villages. OBJECTIVE To assess the knowledge and attitudes of cervical cancer screening among VHVs. MATERIALS AND METHODS The subjects were 128 VHVs from four Nakornnayok sub-districts; namely KlongYai, Chomphol, Buangsan and Suksara, Thailand. The study was conducted from December 2014 to January 2015. The questionnaire was designed to assess the knowledge and attitude of cervical cancer screening provided by the VHVs. In addition, cervical cancer screening coverage rates of each area were collected. The demographic data, scores of knowledge, attitudes, practices and the cervical cancer screening coverage rates were analyzed by one-way ANOVA. RESULTS The questionnaire reliability was assessed as 0.81. The total knowledge and attitude scores were 10 and 15 points. The mean knowledge scores of KlongYai, Chomphol, Buangsan and Suksara were 6.8, 7.0, 6.5 and 9.0 points, respectively. The VHVs had a high level of overall knowledge about cervical cancer screening. The mean attitude scores were 12.4, 13.2, 13.4 and 13.1 points. VHVs had a positive attitude to the promotion of cervical cancer screening at the overall level. The percentages of VHVs promoting cervical cancer information in respective districts were 72.2, 94.3, 94.9 and 50.0. However, the cervical cancer screening coverage rates were 62.4%, 34.7%, 80.3% and 47.3% respectively. CONCLUSIONS The knowledge, attitudes and percentages of promoting information of cervical cancer screening among VHVs in the four sub-districts were high but did not correlate with the cervical screening coverage rates for each area. VHVs needed to understand socio-cultural beliefs of the women in the target population and design suitable strategies to encourage higher cervical screening coverage.
The Timing of Discharge From the Intensive Care Unit and Subsequent Mortality: A Prospective, Multicenter Study

COMMENT An important function of the cardiovascular system is to provide adequate systemic blood flow and perfusion pressure to achieve and maintain organ homeostasis. This goal requires that vasoconstrictor and vasodilator influences be meticulously balanced. However, in “distributive shock,” a vasodilatory state predominates and can cause inadequate end-organ perfusion. Despite satisfactory or even high cardiac output, the lack of vascular tone results in unacceptable, dangerously low endorgan perfusion. Methylene blue is commonly used by clinicians as a dye in assorted medical procedures or, less frequently, to treat nitrateinduced methemoglobinemia. Importantly, the vasoconstrictive effect of MB is manifested only in circumstances of nitric oxide (NO) up-regulation. Hence, increases in blood pressure are not seen when MB is given as a dye during uncomplicated procedures involving nonvasoplegic patients. Nitric oxide binds to and activates the enzyme-soluble guanylate cyclase, forming cyclic guanosine monophosphate (cGMP), which, in turn, eventually produces vascular smooth muscle relaxation. Nitric oxide is continuously produced at low concentrations by the calcium-dependent enzyme NO synthase. Methylene blue directly inhibits NO synthase. It also inhibits the enzyme-soluble guanylate cyclase and prevents accumulation of cGMP. By competitively blocking the target enzyme of NO, MB reduces the responsiveness of vessels to cGMP-dependent vasodilators and restores vascular tone. Increases in intracellular cGMP relax both vascular smooth muscle and myocardial myocytes. This may explain why experimental animal studies have shown that, in addition to reduction in vasopressor requirements, inotropic support is reduced after administration of MB, probably owing to attenuation of ischemia/reperfusion injury. Although MB certainly improves blood pressure, enhanced oxygen delivery or reduced mortality secondary to MB has not yet been confirmed. Given these incomplete data, the authors believe that MB should be used to treat vasoplegia unresponsive to traditional vasopressors, rather than as a first-line agent, until more information becomes available. Clearly, large, randomized controlled trials are urgently required to establish the role of MB in treating vasoplegia.
Analysis of the symmetric shortest queue problem

In this paper we study a system consisting of two identical servers, each with exponentially distributed service times. Jobs arrive according to a Poisson stream. On arrival a job joins the shortest queue and in case both queues have equal lengths, he joins either queue with probability 1/2. By using a compensation method, we show that the stationary queue length distribution can be expressed as an infinite linear combination of product forms. Explicit relations are found for these product forms, as well as for the coefficients in the linear combination. These analytic results offer an elegant and efficient numerical algorithm, with effective bounds on the error of each partial sum.
Energy Efficient Routing in Wireless Sensor Networks

In this paper we introduce a new scheme for the purpose of routing in the wireless sensor networks. Our proposed approach is for the case in which many sensors need to collect data and send it to a central node. We will show that in order to find the routes that give energy efficiency, we can solve a set of partial differential equations similar to the Maxwell’s equations in the electrostatic theory. These partial differential equations give the geographical paths from each sensor to the destination. In order to find the actual routes, we approximate the found paths by a sequence of wireless links each between a pair of sensors. Our simulation results show considerable improvement in the life of the network compared to the traditional shortest path approach.
Low-Penetrance Susceptibility Variants in Familial Colorectal Cancer

Background: Genomewide association studies have identified 10 low-penetrance loci that confer modestly increased risk for colorectal cancer (CRC). Although they underlie a significant proportion of CRC in the general population, their impact on the familial risk for CRC has yet to be formally enumerated. The aim of this study was to examine the combined contribution of the 10 variants, rs6983267, rs4779584, rs4939827, rs16892766, rs10795668, rs3802842, rs4444235, rs9929218, rs10411210, and rs961253, on familial CRC. Methods: The population-based series of CRC samples included in this study consisted of 97 familial cases and 691 sporadic cases. Genotypes in the 10 loci and clinical data, including family history of cancer verified from the Finnish Cancer Registry, were available. The overall number of risk alleles (0-20) was determined, and its association with familial CRC was analyzed. Excess familial risk was estimated using cancer incidence data from the first-degree relatives of the cases. Results: A linear association between the number of risk alleles and familial CRC was observed (P = 0.006). With each risk-allele addition, the odds of having an affected first-degree relative increased by 1.16 (95% confidence interval, 1.04-1.30). The 10 low-penetrance loci collectively explain ∼9% of the variance in familial risk for CRC. Conclusions: This study provides evidence to support the previous indirect estimations that these low-penetrance variants account for a relatively small proportion of the familial aggregation of CRC. Impact: Our results emphasize the need to characterize the remaining molecular basis of familial CRC, which should eventually yield in individualized targeting of preventive interventions. Cancer Epidemiol Biomarkers Prev; 19(6); 1478–83. ©2010 AACR.