Miracle-dz/UniFAR-FTUs huggingface dataset:
Phosphoinositides Affect both the Cellular Distribution and Activity of the F-BAR-containing RhoGAP Rgd1p in Yeast*

Cell polarity is a key element of development in most eukaryotes. The Rho GTPase-activating protein Rgd1p positively regulates the GTPase activity of Rho3p and Rho4p, which are involved in bud growth and cytokinesis, respectively, in the budding yeast Saccharomyces cerevisiae. Rgd1p contains an F-BAR domain at its N-terminal end in addition to its RhoGAP domain at its C-terminal end. We demonstrate here that phospholipids discriminate between the GTPase activities of Rho3p and Rho4p through Rgd1p and specifically stimulate the RhoGAP activity on Rho4p. The central region of the protein contiguous to the F-BAR domain is required for this stimulation. The F-BAR region binds to phosphoinositides in vitro and also plays a key role in the localization of Rgd1p to the bud tip and neck during the cell cycle. Studies of heat-sensitive mutants lacking phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-biphosphate suggested that Rgd1p initially binds to Golgi membranes via phosphatidylinositol 4-phosphate and is then transported to the plasma membrane, where it binds phosphatidylinositol 4,5-biphosphate. We demonstrate here the dual effects of phosphoinositides on a RhoGTPase-activating protein. Phosphoinositides both regulate the recruitment and trafficking of Rgd1p to membranes via the F-BAR domain and specifically stimulate GTPase-activating protein activity, consistent with functional interplay between lipids, RhoGAP, and its related GTPases in yeast growth.
A Dynamic Arterial Tree Phantom for studies of bolus chasing CT Angiography

Computed Tomography (CT) and Magnetic Resonance (MR) imaging techniques have become an important role in diagnosing the vascular diseases. Before a clinical trial of the newly developed techniques, it is essential to evaluate them on a phantom. However, there is no existing arterial tree phantom that serves for flood flows. To that end, we design and develop a Dynamic Arterial Tree Phantom (DATP), which is able to produce many kinds of blood flow pattern through using a programmable pump functions as a heart. Contrast enhanced CT scan is also performed on this phantom for adaptive bolus chasing techniques.
Compressed Sampling for Spike Sorting

Our goal is to demonstrate the usefulness and efficiency of a compressed sensing approach when applied to the problem of spike sorting. This approach involves four steps towards transforming the raw spikes into a sparse basis with the fewest number of measurements require to achieve accurate clustering. We first train a dictionary which converts a spike into a sparse signal. We then sample the signal and reconstruct it into a sparse domain using a standard compressive sensing approach. Finally, we cluster the sparse signal and compare it to our truth data. We demonstrate that we are able to achieve very high cluster purity with our approach, and can do so with a minimal number of samples required from the original signal.
Association between spirometry controlled chest CT scores using computer-animated biofeedback and clinical markers of lung disease in children with cystic fibrosis

ABSTRACT Background: Computed tomography (CT) of the lungs is the gold standard for assessing the extent of structural changes in the lungs. Spirometry-controlled chest CT (SCCCT) has improved the usefulness of CT by standardising inspiratory and expiratory lung volumes during imaging. This was a single-centre cross-sectional study in children with cystic fibrosis (CF). Using SCCCT we wished to investigate the association between the quantity and extent of structural lung changes and pulmonary function outcomes, and prevalence of known CF lung pathogens. Methods: CT images were analysed by CF-CT scoring (expressed as % of maximum score) to quantify different aspects of structural lung changes including bronchiectasis, airway wall thickening, mucus plugging, opacities, cysts, bullae and gas trapping. Clinical markers consisted of outcomes from pulmonary function tests, microbiological cultures from sputum and serological samples reflecting anti-bacterial and anti-fungal antibodies. Results: Sixty-four children with CF, median age (range) of 12.7 (6.4–18.1) years, participated in the study. The median (range) CF-CT total score in all children was 9.3% (0.4–46.8) with gas trapping of 40.7% (3.7–100) as the most abundant finding. Significantly higher median CF-CT total scores (21.9%) were found in patients with chronic infections (N = 12) including Gram-negative infection and allergic bronchopulmonary aspergillosis (ABPA) exhibiting CF-CT total scores of 14.2% (ns) and 24.0% (p < 0.01), respectively, compared to 8.0% in patients with no chronic lung infection. Lung clearance index (LCI) derived from multiple breath washout exhibited closest association with total CF-CT scores, compared to other pulmonary function outcomes. Conclusions: The most prominent structural lung change was gas trapping, while CF-CT total scores were generally low, both showing close association with LCI. Chronic lung infections, specifically in the form of ABPA, were associated with increased scores in lung changes. Further investigation of impact of infections with different microorganisms on extent and progression of structural CF lung disease is needed.
Inhibition of fatty acid synthase is protective in pulmonary hypertension

In pulmonary hypertension (PH), similar to cancer, there is altered energy metabolism, apoptosis resistance and cellular proliferation leading to pulmonary vascular remodelling. Proliferating cells exhibit higher rate of de novo fatty acid synthesis to provide lipids for membrane formation and energy production. As inhibition of de novo fatty acid synthesis proved protective in cancer experimentally, therefore, it was hypothesized that modulation of de novo fatty acid synthesis by inhibition of fatty acid synthase (FAS) may prove beneficial for PH.
A multi-level FREAK DTN: Taking care of disconnected nodes in the IoT

Crowdsensing is, for a few years, a hot topic. Until now, research on crowdsensing mainly focused on scenarios with devices such as smartphones with huge memory and high computive skills. With the development of the Internet of Things (IoT), crowdsensing can be envisaged with other constraints. Indeed, some IoT nodes are mobile but with limitations about storage and processing capabilities, then connectivity disruptions might occur between the nodes. These issues are tackled by a Disruption Tolerant Networking architecture. In this article, we focus on a subset of IoT, Mobile Sensing Networks (MSN). We propose then, a mechanism which respects the constraints of the nodes and maintains high performance. This mechanism, the multi-level FREAK, uses the mean frequency of contacts with the destination. The metrics drives the transmission. Since some nodes might not meet the destination nor nodes meeting the destination, we had the idea of a multi-level metrics to allow these “disconnected” nodes to transmit data to the destination. We evaluate our proposal through simulations based on several real mobility traces. Our solution outperforms reference replication and quota-based DTN solutions.
Simulation Aided Life Cycle Sustainability Assessment Framework for Manufacturing Design and Management

Decision making for sustainable manufacturing design and management requires critical considerations due to the complexity and partly conflicting issues of economic, social and environmental factors. Although there are tools capable of assessing the combination of one or two of the sustainability factors, the frameworks have not adequately integrated all the three factors. Case study and review of existing simulation applications also shows the approach lacks integration of the sustainability factors. In this paper we discussed the development of a simulation based framework for support of a holistic assessment of sustainable manufacturing design and management. To achieve this, a strategic approach is introduced to investigate the strengths and weaknesses of the existing decision supporting tools. Investigation reveals that Discrete Event Simulation (DES) can serve as a rock base for other Life Cycle Analysis frameworks. Simio-DES application optimizes systems for both economic and competitive advantage, Granta CES EduPack and SimaPro collate data for Material Flow Analysis and environmental Life Cycle Assessment, while social and stakeholders’ analysis is supported by Analytical Hierarchy Process, a Multi-Criteria Decision Analysismethod. Such a commonand integratedframework createsa platform for companies to build a computer simulation model of a real system and assess the impact of alternative solutions before implementing a chosen solution.
Blood Rheology Associated with Cardiovascular Risk Factors and Chronic Cardiovascular Diseases: Results of an Epidemiologic Cross-sectional Study

As part of an epidemiologic cross- sectional study to determine cardio vascular (CV) risk factors in the population (total serum cholesterol, smoking, blood pressure, and body weight) hemoglobin (Hb) and plasma viscosity (PV) were measured. A two- stage cluster sample of 5,312 persons, aged twenty-five to sixty-four (availa ble 5,069) was selected from a mixed urban-rural target population of 282,279 inhabitants, from which 4,022 (79.3%) participated in the study. Patients with chronic myocar dial infarction (MI), cerebral infarc tion (CI), angina pectoris (AP), and peripheral arterial disease (PAD) were identified by questionnaire. The results show that there is no age or sex dependency of PV in healthy participants, while hemoglo bin shows the well-known sex differ ence. In contrast, PV increases continuously with age in the total population. In men, increased PV is found in untreated hypertension, in hypercholesterolemia, and in smok ers. In women, it is raised in hyper cholesterolemia and in gross obesity. Male MI patients and patients of both sexes after CI in particular show statistically significantly elevated PV. Finally, in male patients with chronic AP or patients of both sexes with PAD, PV is elevated and a tendency to higher Hb values is seen. These results confirm smaller clinical trials suggesting that blood fluidity is pathologically altered in patients with CV risk factors or dis eases. Since impaired blood fluidity may worsen the hemodynamic situa tion, in particular in patients with limited vasomotor reserve, he morheologic parameters may be of prognostic relevance. Therapeutic implications of these findings should be considered.
Development of an algorithm for using PINP to monitor treatment of patients with teriparatide*

ABSTRACT Introduction: Teriparatide effects are mediated via the preferential stimulation of osteoblastic activity over osteoclastic activity. Amino-terminal propeptide of type I procollagen (PINP) is an indicator of osteoblastic activity. Objective: Develop an algorithm using PINP as an aid in the management of patients with postmenopausal osteoporosis treated with teriparatide. Research design and methods: For inclusion in this post-hoc analysis, trials had to be investigations of teriparatide 20 µg/day in postmenopausal women with osteoporosis having measurements of PINP at 3 months and bone mineral density (BMD) at 12 months. Signal-to-noise ratio was calculated for a series of markers of bone turnover in the Fracture Prevention Trial. An algorithm was developed to monitor patients treated with teriparatide using PINP. Results: Three trials met inclusion criteria and included the Fracture Prevention, Forteo-Alendronate Comparator and Anabolic After Antiresorptive trials. PINP had the highest signal-to-noise ratio of all bone-turnover markers. Positive PINP responses defined as increases > 10 µg/L were observed in 77–97% of teriparatide- and in 6% of placebo-treated patients after 3 months of study drug. Mean lumbar spine BMD increases after 12 months of teriparatide in patients having PINP changes > 10 µg/L ranged from 8.3% to 9.5% and in patients with PINP changes ≤ 10 µg/L ranged from 5.9% to 7.6%. In the algorithm, PINP is measured at baseline and after 1–3 months of therapy. Patients with PINP increases > 10 µg/L are given a positive message. Patients with PINP increases ≤ 10 µg/L are assessed for adherence, teriparatide administration and storage techniques, and for the presence of medical conditions that might limit their therapeutic response, and these issues are addressed as appropriate. Patients without these issues and with PINP increases ≤ 10 µg/L should be given a neutral message because BMD may significantly increase with continued therapy. Conclusions: The PINP algorithm provides information regarding the anabolic response to teriparatide therapy and has the potential to identify patients requiring help with issues of adherence, injection technique, teriparatide storage, and medical problems limiting therapeutic responsiveness to teriparatide treatment. Data assessing the relationship of changes in PINP to fracture risk reduction are not available. We recommend physicians audit the use of the algorithm in practice so that improvements can be made.
Deanonymization in the Bitcoin P2P Network

Recent attacks on Bitcoin's peer-to-peer (P2P) network demonstrated that its transaction-flooding protocols, which are used to ensure network consistency, may enable user deanonymization---the linkage of a user's IP address with her pseudonym in the Bitcoin network. In 2015, the Bitcoin community responded to these attacks by changing the network's flooding mechanism to a different protocol, known as diffusion. However, it is unclear if diffusion actually improves the system's anonymity. In this paper, we model the Bitcoin networking stack and analyze its anonymity properties, both pre- and post-2015. The core problem is one of epidemic source inference over graphs, where the observational model and spreading mechanisms are informed by Bitcoin's implementation; notably, these models have not been studied in the epidemic source detection literature before. We identify and analyze near-optimal source estimators. This analysis suggests that Bitcoin's networking protocols (both pre- and post-2015) offer poor anonymity properties on networks with a regular-tree topology. We confirm this claim in simulation on a 2015 snapshot of the real Bitcoin P2P network topology.
Gait Abnormalities in Elderly Fallers

The objective of this study was to measure gait abnormalities in elderly fallers with the Locometrix™ gait-analysis system. This accelerometric device provided the following gait variables: walking speed and stride frequency, length, symmetry, and regularity. The variables were analyzed over a 20-s period of stable walking on a flat track of 40 m. Participants were 20 elderly patients hospitalized for falls (mean age 80.8 ± 5.0 years) and 33 older adults living at home (mean age 77.2 ± 6.5 years). All gait variables were found to be significantly lower in the faller group (p < .05). The lower gait speed, stride length, and stride frequency were previously recognized as nonrelevant in predicting the risk of falling, whereas lower stride symmetry was related to an underlying pathology and lower stride regularity was correlated to the risk of falls. The Locometrix appears to be well suited to measure gait regularity in routine practice.
USO DE TÉCNICA MULTIVARIADAS PARA ESTUDAR O GÊNERO STYLOSANTHES

The semi-arid region is characterized by low rainfall indices and poor rainfall distribution, which are limiting factors in the agricultural production of the region. For this reason, strategies should be used and the study of plant species adapted to these conditions, with potential forage, has been one of these strategies. Forages of the family fabaceae have great genetic diversity and the genus Stylosanthes, has been shown as a great option in the semiarid region of Brazil. The objective of this study was to evaluate the degree of diversity by means of morphoagronomic descriptors of 26 accessions of the genus Stylosanthes, using multivariate techniques. The experiment was carried out at the Horto Florestal Experimental Unit of the Feira de Santana State University (UEFS), in the city of Feira de Santana, Bahia. Twenty five Stylosanthes genus accessions belonging to the Forage Germplasm Bank of the UEFS (BGF-UEFS) were used and commercializing Estilosantes Campo Grande, used as a control. Seed germination was initially observed and analyzed daily during a period in BOD (Biochemical Oxigen Demand) and as the seeds germinated, the seedlings were placed in the greenhouse. The evaluations were performed 60 days after transplanting, and the following characters were evaluated: Plant Height, Main Leaflet Length, Lateral Leaflet Length, Main Leaflet Width, Lateral Leaflet Width, Stem Diameter, Length and Lateral Width and Relationship between Length and Central Width. An analysis was made considering all the features together (multivariate analysis), performed through computational routines implemented in software R. From this, it was proved that most of the accessions presented more distances when combined with the accesses BGF08065, BGF14-080, BGF08-079, BGF14-96, BGF08-105 showing that they are the most divergent from the general evaluation. However, the least divergent accesses were BGF08-071 and BGF14-087. As for the accessions BGF14-072 and BGF08-073, it was observed a greater similarity between them, since the accesses BGF08-079 and BGF14-091 are the most distant among them. The multivariate analyzes carried out showed that there is genetic variability from the characters studied among the individuals. In this way, it is possible to use these Stylosanthes accessions for future work on plant breeding programs.
miR-451 regulates FoxO3 nuclear accumulation through Ywhaz in human colorectal cancer.

BACKGROUND AND OBJECTIVE Our previous studies reported that miR-451 could protect against erythroid oxidant stress target gene-Ywhaz (14-3-3zeta) via inhibiting FoxO3 in the erythropoiesis. This study aimed to investigate the potential mechanism underlying the regulatory effect of miR-451 on human colorectal cancer (CRC) cells. METHODS In this study, expressions of miR-451 and Ywhaz in CRC tissues and adjacent normal tissues were detected by quantitative real-time PCR (qRT-PCR) and immunohistochemistry respectively. Human colon cancer cell lines were transfected with miR-451-MSCV-PIG retroviral vector to restore miR-451 expression. Ywhaz-3'UTR luciferase reporter assay confirmed Ywhaz as a direct target gene of miR-451. HCT116 cells and H29 cells were transfected with -shRNA-Ywhaz (pSGU6-Ywahz-shRNA-GFP) and the protein level of FoxO3 in the nucleus and cytoplasm was detected via Western blot assay. The anti-tumor effects of miR-451 were further verified in nude mice. RESULTS miR-451 was significantly down-regulated in human colon cancer tissues and cell lines (HCT116 and HT29), and inversely correlated with Dukes stage of colon cancer. Ywhaz was a candidate target gene of miR-451 and able to stimulate tumor growth via binding to FoxO3, inhibiting the FoxO3 nuclear accumulation. CONCLUSION miR-451 may inhibit the colon cancer growth in vitro and in vivo, likely through directly targeting Ywhaz and indirectly regulating the nuclear accumulation of FoxO3.
COMPARISON OF ORGAN DOSES IN HUMAN PHANTOMS: VARIATIONS DUE TO BODY SIZE AND POSTURE

Organ dose calculations performed using human phantoms can provide estimates of astronauts' health risks due to cosmic radiation. However, the characteristics of such phantoms strongly affect the estimation precision. To investigate organ dose variations with body size and posture in human phantoms, a non-uniform rational B-spline boundary surfaces model was constructed based on cryosection images. This model was used to establish four phantoms with different body size and posture parameters, whose organs parameters were changed simultaneously and which were voxelised with 4 × 4 × 4 mm3 resolution. Then, using Monte Carlo transport code, the organ doses caused by ≤500 MeV isotropic incident protons were calculated. The dose variations due to body size differences within a certain range were negligible, and the doses received in crouching and standing-up postures were similar. Therefore, a standard Chinese phantom could be established, and posture changes cannot effectively protect astronauts during solar particle events.
Microwave-assisted Solvent-free Synthesis and in Vitro Antibacterial Screening of Quinoxalines and Pyrido[2, 3b]pyrazines

We report herein the microwave assisted synthesis, without solvents and catalysts, of 6-substituted quinoxalines and 7-substituted pyrido[2,3b]pyrazines. The compounds were obtained in good yields and short reaction times using the mentioned procedure and two new structures are reported. A complete 1H- and 13C-NMR assignment was performed using 1D and 2D-NMR. Additionally, an in vitro screening was performed on Gram-positive and Gram-negative bacteria using amoxicillin as positive reference. Compounds bearing a pyridyl group tended to have higher antibacterial activity, but the best activity against Bacillus subtilis and Proteus mirabilis was observed with quinoxaline derivatives.
Association of RASGRP1 with type 1 diabetes is revealed by combined follow-up of two genome-wide studies

Background: The two genome-wide association studies published by us and by the Wellcome Trust Case–Control Consortium (WTCCC) revealed a number of novel loci, but neither had the statistical power to elucidate all of the genetic components of type 1 diabetes risk, a task for which larger effective sample sizes are needed. Methods: We analysed data from two sources: (1) The previously published second stage of our study, with a total sample size of the two stages consisting of 1046 Canadian case–parent trios and 538 multiplex families with 929 affected offspring from the Type 1 Diabetes Genetics Consortium (T1DGC); (2) the Rapid Response 2 (RR2) project of the T1DGC, which genotyped 4417 individuals from 1062 non-overlapping families, including 2059 affected individuals (mostly sibling pairs) for the 1536 markers with the highest statistical significance for type 1 diabetes in the WTCCC results. Results: One locus, mapping to a linkage disequilibrium (LD) block at chr15q14, reached statistical significance by combining results from two markers (rs17574546 and rs7171171) in perfect LD with each other (r2 = 1). We obtained a joint p value of 1.3×10−6, which exceeds by an order of magnitude the conservative threshold of 3.26×10−5 obtained by correcting for the 1536 single nucleotide polymorphisms (SNPs) tested in our study. Meta-analysis with the original WTCCC genome-wide data produced a p value of 5.83×10−9. Conclusions: A novel type 1 diabetes locus was discovered. It involves RASGRP1, a gene known to play a crucial role in thymocyte differentiation and T cell receptor (TCR) signalling by activating the Ras signalling pathway.
Performance modeling and analysis of object oriented distributed software systems: A necessary step toward software performance stability

Advances in object-oriented (00) technology and distributed computing generate distributed object oriented software systems. Choosing an efficient design of such software is a multi-criteria decision problem. Performance is a key criterion that makes software developers be able to select the system that best fit their requirements and achieve longer design stability. Classical techniques of performance analysis are either unsuitable or unnatural to capture performance behavior of 00 systems. In this paper, we present Performance-Based Model for Distributed 00 Software (DOOS) and a methodology to analyze and evaluate its performance. The new model evaluates the time cost of DOOS system considering the communication overheads while preserving the 00 features such as encapsulations and inheritance.