Miracle-dz/UniFAR-FTUs huggingface dataset:
RNA-seq analysis of blood of valproic acid-responsive and non-responsive pediatric patients with epilepsy

Epilepsy is the most common chronic neurological disorder, affecting ~70 million individuals worldwide. However, approximately one-third of the patients are refractory to epilepsy medication. Of note, 100% of patients with genetic epilepsy who are resistant to the traditional drug, valproic acid (VPA), are also refractory to the other anti-epileptic drugs. The aim of the present study was to compare the transcriptomes in VPA responders and non-responders, to explore the mechanism of action of VPA and identify possible biomarkers to predict VPA resistance. Thus, RNA-seq was employed for transcriptomic analysis, differentially expressed genes (DEGs) were analyzed using Cuffdiff software and the DAVID database was used to infer the functions of the DEGs. A protein-protein interaction network was obtained using STRING and visualized with Cytoscape. A total of 389 DEGs between VPA-responsive and non-responsive pediatric patients were identified. Of these genes, 227 were upregulated and 162 were downregulated. The upregulated DEGs were largely associated with cytokines, chemokines and chemokine receptor-binding factors, whereas the downregulated DEGs were associated with cation channels, iron ion binding proteins, and immunoglobulin E receptors. In the pathway analysis, the toll-like receptor signaling pathway, pathways in cancer, and cytokine-cytokine receptor interaction were mostly enriched by the DEGs. Furthermore, three modules were identified by protein-protein interaction analysis, and the potential hub genes, chemokine (C-C motif) ligand 3 and 4, chemokine (C-X-C motif) ligand 9, tumor necrosis factor-α and interleukin-1β, which are known to be closely associated with epilepsy, were identified. These specific chemokines may participate in processes associated with VPA resistance and may be potential biomarkers for monitoring the efficacy of VPA.
The Quarterly Japanese Economic Model (Q-JEM): 2011 Version

This paper provides a brief explanation and a detailed documentation of the current version of the Quarterly Japanese Economic Model (Q-JEM), which has been developed and constantly updated since the mid-2000s at Research and Statistics Department, Bank of Japan. Q-JEM is a large-scale hybrid-type macroeconomic model that pursues both long-run theoretical coherence and short-run empirical validity, as is the Federal Reserve Board's FRB/US model. The model captures various aspects of Japan's economy, including inflation dynamics, the zero lower bound on nominal interest rates, linkages with overseas economies, and the effects of population aging and declining potential economic growth.
Critical leg ischaemia: an appraisal of clinical definitions

The reliable prediction of imminent limb death remains a clinical problem. The International Vascular Symposium and European working parties each produced similar definitions of “critical ischaemia”, but this is the first attempt to address the issue with prospectively collected data. Complete 3‐year follow‐up data were available for 213 patients. In addition to the above two definitions, a simplified modification has been evaluated, after review of the data 1 year into this study. All three definitions were able to identify patients likely to require amputation in the absence of successful reconstruction. The sensitivity, specificity and positive predictive values with which they were able to do so was, however, poor. None of the definitions was able to predict which diabetic patients would require amputation. Diabetics were more likely to undergo amputation than non‐diabetics. There was, however, no significant difference in the initial ankle artery pressures between the diabetic and non‐diabetic patient subgroups. None of the definitions reliably predicted which grafts would occlude, in which event the 3‐year mortality rate was approximately 35 per cent. Critical ischaemia by any of these definitions is associated with a high mortality rate. Arterial reconstruction is associated with a reduction in both mortality and amputation rates These data do not support the hypothesis that critical ischaemia is associated with a greater graft occlusion rate than lesser degrees of severe ischaemia.
Phytosiderophore Efflux Transporters Are Crucial for Iron Acquisition in Graminaceous Plants

Eukaryotic organisms have developed diverse mechanisms for the acquisition of iron, which is required for their survival. Graminaceous plants use a chelation strategy. They secrete phytosiderophore compounds, which solubilize iron in the soil, and then take up the resulting iron-phytosiderophore complexes. Bacteria and mammals also secrete siderophores to acquire iron. Although phytosiderophore secretion is crucial for plant growth, its molecular mechanism remains unknown. Here, we show that the efflux of deoxymugineic acid, the primary phytosiderophore from rice and barley, involves the TOM1 and HvTOM1 genes, respectively. Xenopus laevis oocytes expressing TOM1 or HvTOM1 released 14C-labeled deoxymugineic acid but not 14C-labeled nicotianamine, a structural analog and biosynthetic precursor of deoxymugineic acid, indicating that the TOM1 and HvTOM1 proteins are the phytosiderophore efflux transporters. Under conditions of iron deficiency, rice and barley roots express high levels of TOM1 and HvTOM1, respectively, and the overexpression of these genes increased tolerance to iron deficiency. In rice roots, the efficiency of deoxymugineic acid secretion was enhanced by overexpression of TOM1 and decreased by its repression, providing further evidence that TOM1 encodes the efflux transporter of deoxymugineic acid. We have also identified two genes encoding efflux transporters of nicotianamine, ENA1 and ENA2. Our identification of phytosiderophore efflux transporters has revealed the final piece in the molecular machinery of iron acquisition in graminaceous plants.
Organic Anion Transporter OAT1 Undergoes Constitutive and Protein Kinase C-regulated Trafficking through a Dynamin- and Clathrin-dependent Pathway*

Organic anion transporter 1 (OAT1) mediates the body disposition of a diverse array of environmental toxins and clinically important drugs. Therefore, understanding the regulation of this transporter has profound clinical significance. We previously demonstrate that OAT1 activity was down-regulated by activation of protein kinase C (PKC), kinetically revealed as a decrease in the maximum transport velocity Vmax without significant change in the substrate affinity Km of the transporter. In the current study, we showed that OAT1 constitutively internalized from and recycled back to the plasma membrane, and PKC activation accelerated OAT1 internalization without affecting OAT1 recycling. We further showed that treatment of OAT1-expressing cells with concanavalin A, depletion of K+ from the cells, or transfection of dominant negative mutants of dynamin-2 or Eps15 into the cells, all of which block the clathrin-dependent endocytotic pathway, significantly blocked constitutive and PKC-regulated OAT1 internalization. We finally showed that OAT1 colocalized with transferrin, a marker for clathrin-dependent endocytosis, at the cell surface and in the EEA1-positive early endosomes. Together, our findings demonstrated for the first time that (i) OAT1 constitutively traffics between plasma membrane and recycling endosomes, (ii) PKC activation down-regulates OAT1 activity by altering already existent OAT1 trafficking, and (iii) OAT1 internalization occurs partly through a dynamin- and clathrin-dependent pathway.
A Goal-oriented Autonomous Controller for Space Exploration

The Autonomous Controller is an on-going activity at ESA ESTEC. The Goal-Oriented Autonomous Controller (GOAC) that will eventually result as an outcome of this activity is envisaged in the frame of future ESA missions wherein on-board autonomy is important. The GOAC is an autonomous controller using a sense-planact paradigm to provide increasing levels of autonomy for robotic task achievement. GOAC will generate plans in situ, deterministically dispatch activities for execution, and recover from off-nominal conditions.
Maternal Vascular Malperfusion and Adverse Perinatal Outcomes in Low-Risk Nulliparous Women.

OBJECTIVE To evaluate the disease burden of placental maternal vascular malperfusion pathology in a low-risk nulliparous population and test the hypothesis that a multiparameter model in the second trimester can predict maternal vascular malperfusion with high precision. METHODS A single-center, prospective cohort study was conducted in healthy nulliparous women. Maternal vascular malperfusion disease burden was estimated by incidence, relative risk (RR), and population-attributable risk percent. Maternal risk factors, serum biomarkers, Doppler, and placental morphologic ultrasonography were examined in isolation and in combination for prediction of this placental pathology. RESULTS The incidence of maternal vascular malperfusion pathology was 8.4% (72/856). Women with pathology had higher risk of preeclampsia (8.33% compared with 1.79%; RR 4.67, 95% CI 1.85-11.77%; population-attributable risk 23.6%, 95% CI 16.9-31.6%), small for gestational age (SGA) (47.22% compared with 9.45%; RR 5.00, 95% CI 3.6-6.93%; population-attributable risk 25.2%, 95% CI 22.1-28.5%), and the composite of adverse outcomes (defined as SGA or preeclampsia) (47.22% compared with 10.59%; RR 4.46, 95% CI 3.25-6.13; population-attributable risk 22.5%, 95% CI 19.8-25.5%). The combination of parameters was superior to individual modalities alone in predicting maternal vascular malperfusion, but achieved only moderate precision (area under the curve 0.77, 95% CI 0.71-0.84). CONCLUSION One in 12 healthy nulliparous women develop maternal vascular malperfusion placental pathology, and these pregnancies had a 4.5 times higher risk of developing preeclampsia or delivering a SGA neonate compared with those without this pathology. A multiparameter model achieved modest precision to predict placental maternal vascular malperfusion. Importantly, in low-risk pregnancies, maternal vascular malperfusion accounts for one fourth of pregnancy outcomes with SGA or preeclampsia. The low population-attributable risk of this placental pathology for SGA and preeclampsia illustrates the importance of discovering novel associations to reduce the disease burden of these pregnancy complications.
Complement 5a‐mediated trophoblasts dysfunction is involved in the development of pre‐eclampsia

Pre‐eclampsia (PE) is a life‐threatening multisystem disorder leading to maternal and neonatal mortality and morbidity. Emerging evidence showed that activation of the complement system is implicated in the pathological processes of PE. However, little is known about the detailed cellular and molecular mechanism of complement activation in the development of PE. In this study, we reported that complement 5a (C5a) plays a pivotal role in aberrant placentation, which is essential for the onset of PE. We detected an elevated C5a deposition in macrophages and C5a receptor (C5aR) expression in trophoblasts of pre‐eclamptic placentas. Further study showed that C5a stimulated trophoblasts towards an anti‐angiogenic phenotype by mediating the imbalance of angiogenic factors such as soluble fms‐like tyrosine kinase 1 (sFlt1) and placental growth factor (PIGF). Additionally, C5a inhibited the migration and tube formation of trophoblasts, while, C5aR knockdown with siRNA rescued migration and tube formation abilities. We also found that maternal C5a serum level was increased in women with PE and was positively correlated with maternal blood pressure and arterial stiffness. These results demonstrated that the placental C5a/C5aR pathway contributed to the development of PE by regulating placental trophoblasts dysfunctions, suggesting that C5a may be a novel therapeutic possibility for the disease.
Designing Messaging to Engage Patients in an Online Suicide Prevention Intervention: Survey Results From Patients With Current Suicidal Ideation

Background Computerized, Internet-delivered interventions can be efficacious; however, uptake and maintaining sustained client engagement are still big challenges. We see the development of effective engagement strategies as the next frontier in online health interventions, an area where much creative research has begun. We also argue that for engagement strategies to accomplish their purpose with novel targeted populations, they need to be tailored to such populations (ie, content is designed with the target population in mind). User-centered design frameworks provide a theoretical foundation for increasing user engagement and uptake by including users in development. However, deciding how to implement this approach to enage users in mental health intervention development is challenging. Objective The aim of this study was to get user input and feedback on acceptability of messaging content intended to engage suicidal individuals. Methods In March 2013, clinic intake staff distributed flyers announcing the study, “Your Feedback Counts” to potential participants (individuals waiting to be seen for a mental health appointment) together with the Patient Health Questionnaire. The flyer explained that a score of two or three (“more than half the days” or “nearly every day” respectively) on the suicide ideation question made them eligible to provide feedback on components of a suicide prevention intervention under development. The patient could access an anonymous online survey by following a link. After providing consent online, participants completed the anonymous survey. Results Thirty-four individuals provided data on past demographic information. Participants reported that they would be most drawn to an intervention where they knew that they were cared about, that was personalized, that others like them had found it helpful, and that included examples with real people. Participants preferred email invitations with subject lines expressing concern and availability of extra resources. Participants also provided feedback about a media prototype including a brand design and advertisement video for introducing the intervention. Conclusions This paper provides one model (including development of an engagement survey, audience for an engagement survey, methods for presenting results of an engagement survey) for including target users in the development of uptake strategies for online mental health interventions.
Performance of turbo coded cooperative asynchronous DS-CDMA in frequency-selective fading channels

We investigate the performance of an uplink turbo-coded cooperative direct-sequence code-division multiple-access (DS-CDMA) system in slow frequency-selective relay channels. The effect of multi-user interference (MUI) is studied where we show that full diversity can only be achieved by using an interference suppression detector. In our cooperative system, perfect and imperfect inter-user channel scenarios are studied. At both the base station and relay, a decorrelator detector and a maximum-ratio combiner (MRC) are employed to decode the received data from different users. Simulation results show that full diversity order of 2P is achieved where P is the number of resolvable paths. Further, we examine the performance of a turbo coded cooperative system using detect-and-forward relaying scheme.
The Effect of Net Foreign Assets on Saving Rate

Observing empirical data we find that many countries try to delay the decision of increasing saving rate in order to avoid a decrease of the living standards. However the delay leads a deterioration of countries financial stability.We present a simple theoretical model that connects between countries saving rate and their net foreign assets. Using cross section data set of 135 countries in 2010 we estimated the econometric relation between saving rate in 2010 as dependent variable and two explanatory variables: the current account in 2010 and the aggregated current account during 1980-2010. Our findings show that industrial countries in a bad financial state tend to decrease their saving rate as external debt is larger causing to deterioration in external debt while countries with good financial state tend to increase their saving rate and the tendency increase as financial state becomes better. Only in countries with a very large external debt saving rate tends to grow. The results point that gross foreign debt will keep increasing and will worsen world financial state causing increased risk of getting into a world crisis.
Effect of feeding whole cereals on performance, starch digestibility and duodenal particle size distribution in broiler chickens

1. An experiment was conducted to study the effects of whole wheat, oats and barley at different inclusion levels on performance, starch digestibility, duodenal particle size distribution, gizzard weight and pH of gizzard contents for broiler chickens. 2. Feed consumption and weight gain were significantly reduced when ground cereals were replaced by whole cereals ( P < 0.05). However, feed conversion efficiency was not affected by inclusion of up to 440 g/kg of whole wheat, and up to 300 g/kg of whole oats and barley. 3. Duodenal particle size was measured by laser diffraction to below 1 μ m in size. A remarkably large proportion of particles were below 100 μ m, with as much as 50% of the particles in the duodenum being below 40 μ m in size. Inclusion of moderate amounts of whole cereals reduced the duodenal mean particle size. Large inclusions of whole cereals decreased ( P < 0.05) the proportion of particles up to 40 μ m in size, and increased ( P < 0.05) the proportion with size between 100 and 300 μ m. 4. Starch digestibility was improved ( P < 0.05) by replacing ground wheat or barley with whole wheat or barley. 5. There was no consistent effect of cereal species or feed form on the pH value of the gizzard contents.
Discursive practices in organizational change

The purpose of this research is to increase understanding of discursive practices in organizational change. By approaching organizational change as a social construction, this dissertation examines how discursive practices are involved in organizational change through a qualitative case study. Current organizational literature demonstrates a discursive turn in which negotiation, interactive meaning creation and tension exploitation through discursive struggles characterize the execution of organizational change. Compared to earlier decades, when change was treated rather mechanistically as a process to be executed in controllable phases, the discursive approach is more capable of examining the social aspects of organizational change in practice. Despite the recent tendency to study change within organizations through the lenses of social constructionism and social constructivism, few scholars have approached discourse directly through practice in the context of organizational change. This study examines aspects that are often taken for granted, such as talk. Discursive practices in organizational change are analysed with a case study method through the practice lens, which views practice as a combination of change practices, change praxis and change practitioners. The narrative analysis of this research in the context of a public university hospital indicates that discursive practices play a role in organizational change through discourse phronesis, the context-dependent practical wisdom of talk, and more specifically through the discursive practices that apply discourse phronesis. Four examples of discursive practices were identified in the case study: field practices, mandate practices, priority practices and word practices. In addition, the agency of the strategy text in translating change was analysed, with the conclusion that while a strategy text is material in nature, it is also a discursive practice which reflects collective identities and their power positions during and as the result of organizational change. The study also suggests that permanent tensions in an organization can be harnessed for the benefit of change through discourse. The dynamic contradiction between permanent tensions and change in an organization is termed the renewal paradox.
Is Indigenous poverty different from other poverty

The Council of Australian Governments (COAG) adopted six targets in 2008 with the main aim to close the life expectancy gap within a generation. Specific goals are in the areas of mortality, access to early childhood education, reading, writing and numeracy achievements, Year 12 attainment and employment disadvantage. While none of the targets explicitly mention poverty, it would be unreasonable to ignore it and the associated financial stress as both are likely to condition the ability to achieve any of the targets identified. For example, standard measures of income poverty illustrates that many Indigenous people may lack the private resources required to facilitate the behaviour required to substantially improve health, attend educational institutions and even to look for and secure suitable work.
Immigrants’ Engagement in Tourism Planning: The Case of the Rouge National Urban Park

Immigrants’ Engagement in Tourism Planning: The Case of the Rouge National Urban Park Anahita Khazaei Advisors: University of Guelph, 2015 Dr. Statia Elliot Dr. Marion Joppe The overarching goal of this research is to provide a deeper understanding of the current approach to immigrants’ engagement in tourism related public decision-making activities and to suggest underlying principles for designing more inclusive community engagement processes. The research was conducted in the context of Canada’s first National Urban Park located in one of the most diverse neighbourhoods in the Greater Toronto Area. An inductive and interpretivist approach was adopted for this study and data were collected from three groups of participants: planners, partner/community organizations, and first generation immigrant community leaders. Semi-structured interviews were conducted as the primary data gathering method, while document analysis served as a secondary method for gaining familiarity with the research context as well as identifying consistencies, inconsistencies, and potential gaps in the data. The research process was informed by the constructivist grounded theory approach (Charmaz, 2006). The first research objective is addressed by exploring participants’ perceptions of the community participation concept as well as identifying building blocks of the current approach to immigrants’ engagement. Insights gained from studying the current situation, as well as additional data on research participants’ suggestions for enhancing immigrants’ engagement, supports the development of underlying principles for more inclusive participation processes. This study contributes to the literature on stakeholder participation in tourism planning in two main ways: first, by conducting empirical research with members of a host community as a heterogeneous stakeholder group; and second, by focusing on immigrants as important yet under-represented and under-studied tourism stakeholders, who contribute considerably to ongoing changes in host communities. It provides a foundation for future studies aiming to improve the scope and quality of community engagement by addressing the challenges of dynamic and diverse future communities. In practice, research findings will help planners to facilitate and enhance immigrants’ participation in tourism planning.