Miracle-dz/UniFAR-FTUs huggingface dataset:
Assembly of filopodia by the formin FRL2 (FMNL3)

Actin‐dependent finger‐like protrusions such as filopodia and microvilli are widespread in eukaryotes, but their assembly mechanisms are poorly understood. Filopodia assembly requires at least three biochemical activities on actin: actin filament nucleation, prolonged actin filament elongation, and actin filament bundling. These activities are shared by several mammalian formin proteins, including mDia2, FRL1 (also called FMNL1), and FRL2 (FMNL3). In this paper, we compare the abilities of constructs from these three formins to induce filopodia. FH1‐FH2 constructs of both FRL2 and mDia2 stimulate potent filopodia assembly in multiple cell types, and enrich strongly at filopodia tips. In contrast, FRL1 FH1‐FH2 lacks this activity, despite possessing similar biochemical activities and being highly homologous to FRL2. Chimeric FH1‐FH2 experiments between FRL1 and FRL2 show that, while both an FH1 and an FH2 are needed, either FH1 domain supports filopodia assembly but only FRL2's FH2 domain allows this activity. A mutation that compromises FRL2's barbed end binding ability abolishes filopodia assembly. FRL2's ability to stimulate filopodia assembly is not altered by additional domains (GBD, DID, DAD), but is significantly reduced in the full‐length construct, suggesting that FRL2 is subject to inhibitory regulation. The data suggest that the FH2 domain of FRL2 possesses properties not shared by FRL1 that allow it to generate filopodia. © 2010 Wiley‐Liss, Inc.
A sample size computation method for non‐linear mixed effects models with applications to pharmacokinetics models

We propose a simple method to compute sample size for an arbitrary test hypothesis in population pharmacokinetics (PK) studies analysed with non‐linear mixed effects models. Sample size procedures exist for linear mixed effects model, and have been recently extended by Rochon using the generalized estimating equation of Liang and Zeger. Thus, full model based inference in sample size computation has been possible. The method we propose extends the approach using a first‐order linearization of the non‐linear mixed effects model and use of the Wald χ2 test statistic. The proposed method is general. It allows an arbitrary non‐linear model as well as arbitrary distribution of random effects characterizing both inter‐ and intra‐individual variability of the mixed effects model. To illustrate possible uses of the method we present tables of minimum sample sizes, in particular, with an illustration of the effect of sampling design on sample size. We demonstrate how (D‐) optimal or frequent sampling requires fewer subjects in comparison to a sparse sampling design. We also present results from Monte Carlo simulations showing that the computed sample size can produce the desired power. The proposed method greatly reduces computing times compared with simulation‐based methods of estimating sample sizes for population PK studies. Copyright © 2004 John Wiley & Sons, Ltd.
Hippocampal hemispheric and long‐axis differentiation of stimulus content during episodic memory encoding and retrieval: An activation likelihood estimation meta‐analysis

While there is ample evidence that the hippocampus is functionally heterogeneous along its longitudinal axis, there is still no consensus regarding its exact organization. Whereas spatial memory tasks frequently engage the posterior hippocampus, the regions engaged during episodic memory are more varying and may depend on the specific nature of the stimuli. Here, we investigate the effect of stimulus content on the location of hippocampal recruitment during episodic memory encoding and retrieval of pictorial and verbal material with a meta‐analysis approach, using activation likelihood estimation and restricting the analysis to the hippocampus. Verbal material was associated with left‐lateralized anterior activation, compared to pictorial material that recruited a more posterior aspect of the hippocampus, primarily within the right hemisphere. This effect held for encoding of both single items and item–item associations but was less clear during retrieval. The findings lend further support to a functional subdivision of the hippocampus along its longitudinal axis and indicate that the content of episodic memories is one factor that determines the location of hippocampal recruitment. © 2015 Wiley Periodicals, Inc.
Taming the Beast: Tailored Therapy for Hepatitis E in Organ Transplant Recipients.

E merging viral infections are often clinical conundrums after solid organ transplantation. Numerous such infections have presented with atypical or unusual symptoms in transplant recipients, including hepatitis E virus (HEV), lym-phocytic choriomeningitis virus, adenovirus, West Nile virus, dengue fever, and multiple others. The HEV, a nonenveloped, positive-sense, single-stranded RNAvirus, results in an estimated 20 million HEV infections annually, with over 3 million acute cases and 56,600 related deaths.
Global Exponential Stability for Uncertain Delayed Neural Networks of Neutral Type With Mixed Time Delays

The global exponential stability for a class of uncertain delayed neural networks (DNNs) of neutral type with mixed delays is investigated in this paper. Delay-dependent and delay-independent stability criteria are proposed to guarantee the robust stability and uniqueness of equilibrium point of DNNs via linear matrix inequality and Razumikhin-like approaches. Two classes of perturbations on weighting matrices are considered in this paper. Some numerical examples are illustrated to show the effectiveness of our results.
mRNA and Small RNA Transcriptomes Reveal Insights into Dynamic Homoeolog Regulation of Allopolyploid Heterosis in Nascent Hexaploid Wheat[W][OPEN]

Newly synthesized allohexaploid wheat lines, which exhibit hybrid vigor or heterosis, may recapitulate the initial genetic state of common wheat. This work shows that, in addition to nonadditive expression, parental expression-level dominance of subgenomes in nascent allohexaploid wheat may contribute distinctively to heterosis through dynamic small RNA–mediated homoeolog regulations. Nascent allohexaploid wheat may represent the initial genetic state of common wheat (Triticum aestivum), which arose as a hybrid between Triticum turgidum (AABB) and Aegilops tauschii (DD) and by chromosome doubling and outcompeted its parents in growth vigor and adaptability. To better understand the molecular basis for this success, we performed mRNA and small RNA transcriptome analyses in nascent allohexaploid wheat and its following generations, their progenitors, and the natural allohexaploid cultivar Chinese Spring, with the assistance of recently published A and D genome sequences. We found that nonadditively expressed protein-coding genes were rare but relevant to growth vigor. Moreover, a high proportion of protein-coding genes exhibited parental expression level dominance, with genes for which the total homoeolog expression level in the progeny was similar to that in T. turgidum potentially participating in development and those with similar expression to that in Ae. tauschii involved in adaptation. In addition, a high proportion of microRNAs showed nonadditive expression upon polyploidization, potentially leading to differential expression of important target genes. Furthermore, increased small interfering RNA density was observed for transposable element–associated D homoeologs in the allohexaploid progeny, which may account for biased repression of D homoeologs. Together, our data provide insights into small RNA–mediated dynamic homoeolog regulation mechanisms that may contribute to heterosis in nascent hexaploid wheat.
African stock markets integration: an analysis of the relationship between major stock markets in Africa

This paper examines the dynamic relationships between thirteen major stock markets in Africa in normal times and in times of financial crises using the Johansen cointegration and Granger causality methodologies. The empirical results revealed evidence of time-varying relationships among African stock markets. While the long-run relationships among the markets were strong prior to the 2007 global financial crisis (GFC) and during the Eurozone sovereign debt crisis (ESDC) periods, the relationships were severely weakened during the period of the GFC. The result also revealed a high degree of short-run dynamic causal relationships among African stock markets during both crises periods compared to the pre-crisis period.
A Novel Type I Cytokine Receptor Is Expressed on Monocytes, Signals Proliferation, and Activates STAT-3 and STAT-5*

Here we report the cloning of a novel type I cytokine receptor, gp130-like monocyte receptor (GLM-R), with homology to the interleukin-6 receptor signal transducing chain, gp130, and granulocyte colony-stimulating factor receptor. Human and murine GLM-R cDNAs encode open reading frames of 732 and 716 amino acids, respectively, and the corresponding genes are located in close proximity to gp130 genes on human chromosome 5 and mouse chromosome 13. GLM-R is specifically expressed on CD14-positive cells and is up-regulated more than 50-fold upon activation of those cells. To address the question of whether GLM-R is a signaling receptor, we constructed a chimeric molecule, consisting of the extracellular domain of human growth hormone (hGH) receptor, and the intracellular domain of GLM-R. When transfected into factor-dependent 32D cells, this chimeric molecule could signal for proliferation and activate signal transducer and activator of transcription (STAT)-3 and STAT-5 upon stimulation with hGH. Thus, GLM-R is a novel signaling receptor chain potentially involved in the development and function of monocytes and macrophages.
"Brain Screen": A self-referral, screening program for strokes, falls and dementia risk factors.

BACKGROUND Falls, strokes and dementia can be predicted and their occurrence can be delayed or even prevented by treatment of risk factors. The value of screening self-referred adults is unknown. OBJECTIVES To assess whether a screening program of self-referred adults provides new and valuable medical information on risk factors for falls, stroke and dementia. METHOD We examined 514 self-referred people (59% women, mean age 68+/-8 years (range 44-89) and 14+/-3 years of education) in our "Brain Screen" program. Participants completed detailed questionnaires and underwent a neurological examination, computerized gait analysis, carotid Duplex, serum lipid and homocysteine levels, a computerized neuropsychological battery (NeuroTrax) and the Mini-Mental State Exam. Information that was detected by "Brain Screen" was compared with the self-reported data. RESULTS Unknown vascular risk factors detected by ""Brain Screen" included: high cholesterol in 44%, homocysteine > 10 micromol/L in 20%, >1 mm carotid intima-media thickness in 13%, and carotid narrowing (> 30%) in 2.2%. Unknown risk factors for falls were detected in 66% of the subjects who never fell. Of the 205 subjects (44%) who complained of memory decline, 28% had objective memory disturbances compared with their age group. Mild cognitive impairment (amnestic MCI) was clinically diagnosed in 17% of the population and dementia in 5%. CONCLUSION Screening self-referred adults for falls, strokes and dementia risk factors detected significant unknown risk factors that can be treated in more than one-third of the participants. A national "Brain Screen" program can have significant impact on the health of the aging population.
Adaptation to Distorted Frequency-to-Place Maps: Implications of Simulations in Normal Listeners for Cochlear Implants and Electroacoustic Stimulation

The ideal cochlear implant electrode array positioning enables stimulation over a range of cochlear positions whose characteristic frequencies cover the frequency range of speech and match the speech processor filter frequencies. However, the electrode positions achieved in practice may not meet this specification. Users of conventional monaural cochlear implants seem able to perceptually adapt to a mismatch of speech processor filters to electrode positions. In electroacoustic stimulation, it is important to consider possible inconsistencies between acoustic and electrical frequency-to-place mapping. Two simulation studies are outlined that address normal listeners’ ability to perceive speech presented through distorted frequency maps. The first presented a map that is spectrally warped around a 10-mm medial cochlear area. Listeners were able to adapt to this map after a few hours of training. The second study presented a binaural mapping in which one ear was subject to a 6-mm basalward shift. Here listeners were unable to learn to integrate speech information across the two mismatched ears, rather they seem to learn to ignore the shifted information. Frequency-to-place mapping is likely to be an important factor in the successful use of a combination of electrical and acoustic hearing.
Detection of phosphotyrosine-containing proteins in polyomavirus middle tumor antigen-transformed cells after treatment with a phosphotyrosine phosphatase inhibitor

Cells transformed with the middle tumor antigen (mT) of polyomavirus were treated with sodium orthovanadate (Na3VO4), an inhibitor of phosphotyrosine phosphatases, to enhance for the detection of cellular proteins which are phosphorylated on tyrosine. Na3VO4 treatment of mT-transformed rat F1-11 cells resulted in a 16-fold elevation in the level of phosphotyrosine associated with total cellular proteins. Parental F1-11 cells displayed only a twofold increase in phosphotyrosine following Na3VO4 treatment. The abundance of phosphotyrosine in Na3VO4-treated mT-transformed F1-11 cells was twofold higher than in untreated Rous sarcoma virus (RSV)-transformed F1-11 cells and 3.5-fold lower than in Na3VO4-treated RSV-transformed F1-11 cells. Tyrosine phosphorylation of many cellular proteins, including p36, the major substrate of the RSV pp60v-src protein, was detected in Na3VO4-treated mT-transformed F1-11 cells at levels comparable to those observed in RSV-transformed cells. Some of the major protein species recognized by antiphosphotyrosine antibodies in Na3VO4-treated mT-transformed cells displayed electrophoretic mobilities similar to those detected in RSV-transformed F1-11 cells. Tyrosine phosphorylation of p36 was also detected in fibroblasts infected with polyomavirus. There was no detectable difference in the kinase activity of pp60c-src:mT extracted from untreated and Na3VO4-treated mT-transformed cells; however, Na3VO4 treatment of F1-11 and mT-transformed F1-11 cells was shown to inhibit the activity of phosphotyrosine phosphatases in a crude assay of total cellular activity with pp60v-src as the substrate. Thus, Na3VO4 treatment may allow the detection of phosphotyrosine-containing proteins in mT-transformed cells by preventing the turnover of phosphate on substrates phosphorylated by activated cellular protein-tyrosine kinases associated with mT. These results suggest that tyrosine phosphorylation of cellular proteins may be involved in the events that are responsible for mT-induced cellular transformation.
A social epidemiology workshop in Central America: Advancing a regional policy on research for health

Milla MA, Universidad Católica de Honduras, Honduras; Monroy-Valle M, Universidad de San Carlos de Guatemala; Agudelo-Suárez AA, Grupo de Investigación sobre la Salud Pública, Universidad de Alicante España y la Facultad de Odontología de Universidad de Antioquía, Colombia; Cuervo LG, Organización Panamericana de la Salud, Organización Mundial de la Salud; Bann D, Universidad College London en el Reino Unido, Burrone MS, Universidad Nacional de Córdoba, Argentina; O’campo P, Universidad de Toronto, Canadá. michelemonroyv@yahoo.com
A Probabilistic Method for Energy Storage Sizing Based on Wind Power Forecast Uncertainty

A novel method is proposed for designing an energy storage system (ESS) which is dedicated to the reduction of the uncertainty of short-term wind power forecasts up to 48 h. The investigation focuses on the statistical behavior of the forecast error and the state of charge (SOC) of the ESS. This approach gives an insight into the influence of the forecast conditions (horizon, quality) on the distribution of SOC. With this knowledge, an optimized sizing of the ESS can be done with a well-defined uncertainty limit. For this study, one-year time series of power output measurements and forecasts were available for two wind farms. As a reference, different forecast quality degrees are simulated based on a persistence approach. With the forecast data, empirical probability density functions (pdfs) are generated which are the basis of the proposed method. This approach can lead to a considerable reduction of the ESS and provides important information about the unserved energy. This unserved energy represents the remaining forecast uncertainty. As a consequence, the proposed probabilistic method permits the sizing of energy storage systems as a function of the desired remaining forecast uncertainty, reducing simultaneously power and energy capacity.
Perceived fear, empathy and financial donations to charitable services

ABSTRACT Charities are non-profit services that address diverse social needs. As securing financial donations is critical to their continued operation, they engage in a range of fund-raising activities. Central to successful fund-raising is understanding what motivates people to give money. Thus, this research investigates the role of donors’ perceived fear and empathy, and how these influence the size of self-reported financial donations. Findings from the initial qualitative study (n = 32) informed the subsequent national quantitative main study (n = 400). Logistic regression revealed perceived fear and empathy as significant predictors, with perceived fear playing a lesser role and empathy playing a greater role in the self-reported donation of larger amounts of money to charities. These findings can assist charities with maximising their fund-raising efforts considering the growing competition for donors’ dollars, enabling them to provide a range of services which benefit society.
Throughput capacity of ALOHA MANETs

One major obstacle stunting the development and application of mobile ad hoc networks (MANETs) is the lack of a thorough understanding on the throughput capacity of these networks. Preliminary works regarding the exact capacity study of MANETs mainly focus on cell-partitioned networks, an oversimplified network model for practical MANETs. This paper studies the exact throughput capacity under a more realistic and practical network model for MANETs, where network nodes randomly move in a continuous unit square without cell-partition and a slotted ALOHA protocol is adopted for medium access control. For the considered ALOHA MANETs (A-MANETs), we first determine its exact throughput capacity based on the successful transmission probability (STP) and also derive the expected end-to-end delay for a capacity achieving routing algorithm. We then develop efficient closed-form approximations to both the STP and the exact throughput capacity in the concerned A-MANET under a popular local transmission scheme, based on which the corresponding capacity optimization issue is explored. Finally, simulation and numerical results are provided to validate the efficiency of our capacity model and to illustrate our theoretical findings.
Vessel segmentation of retinal image based on pixel strength and multi-agent

Accurate vessel segmentation in retinal images prove to be a challenging process due to variations of intensity distribution and small scale of vessels, and development of clinically applicable analysis tools presents even more difficult tasks. Major obstacles include detection of very small vessels. This paper reports on a unique approach to these problems, which defines a simple but effective feature concept called pixel strength, and applies a combination of global and local methods as well as post-processing based on multi-agent. The proposed algorithm was tested using DRIVE database, whose results showed consistent performance improvement over existing solutions we have seen in literature. The effectiveness and robustness of the method were also proved with clinical images. The vessel segmentation results demonstrated its near readiness to be deployed and used for clinical studies of retinopathy.
Prehospital administration of P2Y12 inhibitors and early coronary reperfusion in primary PCI: an observational comparative study

Summary The newer oral P2Y12 inhibitors prasugrel and ticagrelor have been reported to be more potent and faster-acting antiplatelet agents than clopidogrel. This study aimed to investigate whether prehospital loading with prasugrel or ticagrelor improves early coronary reperfusion as compared to prehospital loading with clopidogrel in a real-world ST-elevation myocardial infarction (STEMI) setting. Over a 70-month period, 3497 patients with on-going STEMI of less than 6 hours and without cardiac arrest or cardiogenic shock underwent primary percutaneous coronary intervention (PPCI) at our centre. The primary endpoint of this study was the proportion of patients who did not meet the criteria for TIMI (Thrombolysis In Myocardial Infarction) flow grade 3 in the infarct-related artery at initial angiography before PPCI. Pre-hospital loading with prasugrel (n = 883) or ticagrelor (n = 491) did not significantly improve coronary reperfusion as compared to prehospital loading with clopidogrel (n = 1,532) – a TIMI-flow 3 at initial angiography was absent in 71.7 %, 69.0 % and 71.5 % of patients, respectively. Major adverse cardiac event (MACE) rates were low at 30 days (3.4 % to 4.0 %) and did not significantly differ between the different P2Y12 inhibitor regimens. In conclusion, this large observational, non-randomised study is the first to show that prehospital loading with the newer P2Y12 inhibitors does not improve early coronary reperfusion as compared to prehospital loading with clopidogrel in a PPCI cohort excluding cardiac arrest and cardiogenic shock.
How trade in ecotourism services can save nature: a policy scenario analysis

ABSTRACT This article considers a developing country which is abundant in a non-renewable natural resource but scarce in industrial goods. The resource can be used for consumption or for exporting ecotourism services. The article examines scenarios in which technical progress, rising demand for tourism services and higher preferences for the environment reduce today's optimal depletion of the resource. Myopic behaviour and future terms-of-trade gains, however, encourage overexploitation of the resource. As a remedy, the article derives the socially optimal subsidy for the conservation of the resource and discusses North–South transfer schemes which save nature via trade in ecotourism services. Numerical examples suggest that under optimistic assumptions a subsidy rate of about 10% would suffice to preserve the natural resource in the developing country for the provision of tourism services. The resulting cost burden would represent less than 0.03% of the Northern GDP.