Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic Characterization of Metformin Hepatic Response

Metformin is used as a first-line therapy for type 2 diabetes (T2D) and prescribed for numerous other diseases. However, its mechanism of action in the liver has yet to be characterized in a systematic manner. To comprehensively identify genes and regulatory elements associated with metformin treatment, we carried out RNA-seq and ChIP-seq (H3K27ac, H3K27me3) on primary human hepatocytes from the same donor treated with vehicle control, metformin or metformin and compound C, an AMP-activated protein kinase (AMPK) inhibitor (allowing to identify AMPK-independent pathways). We identified thousands of metformin responsive AMPK-dependent and AMPK-independent differentially expressed genes and regulatory elements. We functionally validated several elements for metformin-induced promoter and enhancer activity. These include an enhancer in an ataxia telangiectasia mutated (ATM) intron that has SNPs in linkage disequilibrium with a metformin treatment response GWAS lead SNP (rs11212617) that showed increased enhancer activity for the associated haplotype. Expression quantitative trait locus (eQTL) liver analysis and CRISPR activation suggest that this enhancer could be regulating ATM, which has a known role in AMPK activation, and potentially also EXPH5 and DDX10, its neighboring genes. Using ChIP-seq and siRNA knockdown, we further show that activating transcription factor 3 (ATF3), our top metformin upregulated AMPK-dependent gene, could have an important role in gluconeogenesis repression. Our findings provide a genome-wide representation of metformin hepatic response, highlight important sequences that could be associated with interindividual variability in glycemic response to metformin and identify novel T2D treatment candidates.
Noninvasive brain stimulation after stroke: it is time for large randomized controlled trials!

PURPOSE OF REVIEW We here provide an update about studies published recently in the field of noninvasive neuromodulation of the motor system, aiming at facilitating recovery of function after stroke. RECENT FINDINGS A number of longitudinal studies have confirmed that repeated stimulation of the motor cortex in combination with motor training improves performance compared with control or sham stimulation. In the early postacute stroke phase, enhancement of ipsilesional motor cortex excitability by means of repetitive transcranial magnetic stimulation (rTMS) seems to be a well tolerated and effective strategy to promote motor recovery. In contrast, recent studies suggest that transcranial direct current stimulation (tDCS) in the early poststroke phase does not facilitate motor recovery. In the chronic phase, however, both rTMS and tDCS have been shown to be beneficial when applied over several days combined with training. Interestingly, bihemispheric stimulation strategies (ipsilesional activation and contralesional suppression) seem to constitute effective protocols, especially when using rTMS. SUMMARY Noninvasive brain stimulation seems to support motor recovery. However, to date randomised controlled trials (RCTs) that are sufficiently powered are lacking. Data suggest that the most promising protocols should now be tested in RCTs with sufficiently large samples taking into account the clinical heterogeneity of stroke.
Vital functions of Apoptosis Inducing Factor (AIF)

In many models of programmed cell death, the mitochondrial protein AIF translocates to the nucleus, where it induces the chromatin condensation and DNA degradation. However, today it is well established that this flavoprotein is bifunctional. In addition to its lethal function in the nucleus of dying cells, AIF plays a vital bioenergetic role in healthy ones by regulating mainly the activity of the mitochondrial respiratory chain complex I. Hypomorphic or deletion mutants of AIF have led to the generation of the first reliable mouse model of complex I deficiency syndrome, which leads to progressive ataxia and blindness due to neuronal degeneration, as well as a dilated cardiomyopathy, skeletal muscle atrophy and metabolic dysfunction. Here, we discuss recent progress in the quest to understand AIF’s involvement in cell survival and in the regulation of mitochondrial respiratory chain complex I.
The Business Genome Project and the advancement of business practice

Purpose – Business innovation comes from combining, recombining and modifying existing ideas, knowledge and know‐how in new ways. The purpose of this paper is to describe an approach to accelerating the business innovation process by priming the combining and recombining process, called the Business Genome Project (BGP). Design/methodology/approach – Business innovation and evolution is compared to cultural and biological evolution and the Human Genome Project (HGP) is used as a template for developing the business genome concept, which involves identifying and mapping the building blocks of extant businesses.Findings – The paper describes a way of priming the innovation pump by aiding the identification and sharing of key business ideas, knowledge and know‐how across firms, organisations, industries, technologies and nations. Recent developments in internet‐based technologies, like Wikipedia and the Encyclopedia of Life, suggest the project is feasible.Practical implications – The BGP can provide a fundam.
How selection forces dictate the variant surface antigens used by malaria parasites

Red blood cells infected by the malaria parasite Plasmodium falciparum express variant surface antigens (VSAs) that evade host immunity and allow the parasites to persist in the human population. There exist many different VSAs and the differential expression of these VSAs is associated with the virulence (damage to the host) of the parasites. The aim of this study is to unravel the differences in the effect key selection forces have on parasites expressing different VSAs such that we can better understand how VSAs enable the parasites to adapt to changes in their environment (like control measures) and how this may impact the virulence of the circulating parasites. To this end, we have built an individual-based model that captures the main selective forces on malaria parasites, namely parasite competition, host immunity, host death and mosquito abundance at both the within- and between-host levels. VSAs are defined by the net growth rates they infer to the parasites and the model keeps track of the expression of, and antibody build-up against, each VSA in all hosts. Our results show an ordered acquisition of VSA-specific antibodies with host age, which causes a dichotomy between the more virulent VSAs that reach high parasitaemias but are restricted to young relatively non-immune hosts, and less virulent VSAs that do not reach such high parasitaemias but can infect a wider range of hosts. The outcome of a change in the parasite's environment in terms of parasite virulence depends on the exact balance between the selection forces, which sets the limiting factor for parasite survival. Parasites will evolve towards expressing more virulent VSAs when the limiting factor for parasite survival is the within-host parasite growth and the parasites are able to minimize this limitation by expressing more virulent VSAs.
Test Strategies for Reconfigurable Scan Networks

On-chip infrastructure is an essential part of today's complex designs and enables their cost-efficient manufacturing and operation. The diversity and high number of infrastructure elements demands flexible and low-latency access mechanisms, such as reconfigurable scan networks (RSNs). The correct operation of the infrastructure access itself is highly important for the test of the system logic, its diagnosis, debug and bring-up, as well as post-silicon validation. Ensuring correct operation requires the thorough testing of the RSN.Because of sequential and combinational dependencies in RSN accesses, test generation for general RSNs is computationally very difficult and requires dedicated test strategies. This paper explores different test strategies for general RSNs and discusses the achieved structural fault coverage. Experimental results show that the combination of functional test heuristics together with a dedicated RSN test pattern generation approach significantly outperforms the test quality of a standard ATPG tool.
Run length coding based new approach to automatic image thresholding

Image thresholding (or binarization) is a basic type of image segmentation capability. To represent binary image objects, run length coding (RL) is frequently utilized. The RL-based adaptive approach is used as a binarization method to obtain the satisfied image intensity discontinuity. Having obtaining the adjustable RL, a multilayer network based on fuzzy inference mechanism is utilized to determine the optimal threshold by use of the global feature measures of the original image. The implementation results show that very visually satisfied results are obtained by the authors' approach. Comparison with other thresholding methods shows that the generalized RL method is able to determine visually satisfied threshold, to reserve the desired detail texture of original image, and is insensitive to various noises in original images. <<ETX>>
The NSW (Australia) Planning Reforms and their Implications for Planning Education and Natural and Built Environment

Planning reforms in NSW have gathered pace. In the past few years, the state government has churned out a series of reforms. These reforms are becoming more urgent in their rhetoric and more dramatic in their impacts. The reforms have included planFrist, BASIX, standardization of LEP, changes to the major projects regime, and changes to the development contribution system. Near the end of 2007, another set of major reforms was proposed through a discussion paper, and some of these reforms have already been speedily legislated. These reforms are being enacted to achieve economic efficiency through uniformity in the planning system across jurisdictions, simplicity and speed for the developers, delivery through electronic systems (ePlanning), development assessment by independent panels and private certifiers, and flexibility via voluntary mechanisms (planning agreements). It has been argued that the reforms are necessary because they are taking place internationally and in other parts of Australia. Contrarily, some sections of the society feel that the reforms are a power grab by the state government or that they are an outcome of the strong influence of the development lobby. On the other hand, a number of planning scholars believe planning reforms are a natural and inevitable outcome of the ascendance of the neo-liberal economic order of the past two to three decades. This paper reviews the motivations behind planning reforms and discuses the profound implications that changes in the planning system in NSW have for natural and built environments in the state.
Non-Suicidal Self Injury, Psychopathology and Attachment: A Study with University Students

Abstract Conducted with a community sample, this study first tested the hypothesis that the constant association of Non-Suicidal Self Injury (NSSI) with various psychopathological states may be overrepresented because many of the studies reporting these associations used clinical samples. Secondly, the study aimed to test the emotional regulation model of NSSI by exploring the functions, the affective antecedents and consequences of NSSI episodes and to understand this emotion regulation role of NSSI in the light of Attachment Theory by differentiating self-injurers and non-self-injurers on relevant romantic attachment dimensions. A third purpose of this study was to test the hypothesis that individuals currently performing NSSI could be differentiated on these dimensions from those who had ceased engaging in NSSI. Pursuing these purposes, 518 university students (171 males and 347 females), aged 17 to 62 years old completed the Self-Injury Questionnaire – Treatment Related (Claes & Vandereycken, 2007), the Brief Symptom Inventory (Derogatis, 1982) and the Adult Attachment Scale (Collins & Read, 1990). Individuals with NSSI scored significantly higher on all BSI subscales (all p < .001). Results also revealed the existence of significant differences between participants with and without NSSI on Anxiety (Z = –2.92, p < .01) and Comfort with Proximity (Z = –3.18, p < .01), and significant differences between past self-injurers and current self-injurers on Trust in Others (Z = –2.40, p < .05). These results are discussed by linking NSSI and Attachment Theory literatures.
İkili ve Çok Taraflı Anlaşmaların Türkiye’nin İhracatı Üzerindeki Etkisi

Whether bilateral and multilateral trade and economic agreements has effect on Turkey’s export to 113 countries is tested between 1996-2006 and within Gravity Model framework. Results show that while bilateral agreements has no statistically significant effect on Turkey’s export, except for Customs Union, multilateral agreements have statistically significant and positive effect on Turkey’s export.
Language of Tourism Advertising: A Pragmatic Approach

Much of the existing research on tourism advertising has focused on visual semiotics rather than verbal language. This research note discusses the methodological approach that was taken to investigate language use in British tourism print advertising. Pragmatics, a branch of linguistics, was utilized to support the content analysis of figures of speech. This methodological approach is the first serious attempt to explore the language use in tourism advertising. The approach taken provides rich insight into the interpretation of figures of speech and demonstrates how language contributes to the communication of tourism images. The major contribution of this research lies in the detailed textual analysis of figures of speech. This analysis is based on pragmatic approach, relevance theory, which enhances the interpretation of tourism images.
Detection of prostaglandin E2‐induced dendritic cell migration into the lymph nodes of mice using a 1.5 T clinical MR scanner

The control of dendritic cell (DC) migration into lymph nodes (LNs) is important for the development of more effective DC‐based immunotherapies. This study was undertaken to evaluate, dynamically and noninvasively, prostaglandin E2 (PGE2)‐enhanced migration of DCs using a 1.5 T clinical MR scanner. DC2.4 cells were labeled with superparamagnetic iron oxide (SPIO), a clinically approved MRI contrast agent. DCs were stimulated with tumor necrosis factor‐α and interferon‐γ in the presence or absence of PGE2. Before and after subcutaneous injection of labeled DCs into the hind leg footpads of mice, MRI detailing the extent of DC migration into popliteal LNs was performed using a 1.5 T clinical MR scanner. SPIO labeling did not influence the viability, endocytic activity, migratory ability and/or co‐stimulatory molecule expression of DCs. PGE2 enhanced significantly chemokine receptor‐7 expression and the migration of DCs (p < 0.05). After subcutaneous injection of DCs, there were decreases in MR signal intensity in popliteal LNs at 24 h post‐injection; in PGE2‐treated cells, the MR signal intensity was significantly lower (decrease of 86.6 ± 2.5%) than in PGE2‐untreated cells (decrease of 70.0 ± 4.2%) (p < 0.05). Histological analyses with the conventionally used Prussian blue stain demonstrated that the PGE2‐treated DCs migrated more deeply into the center of LNs. PGE2‐enhanced migration of SPIO‐labeled DCs into LNs can be detected using a 1.5 T clinical MR scanner. Our results suggest that in vivo MRI of DC migration is a useful imaging method to predict DC therapy with a high rate of efficacy and to improve DC‐based immunotherapy, thereby reducing costs compared with current treatments in clinical trials. Copyright © 2011 John Wiley & Sons, Ltd.
Using Incentives to Change How Teenagers Spend Their Time: The Effects of New York City's Conditional Cash Transfer Program

This report presents the results of an innovative study designed to provide a more detailed understanding of how parents and their teenage children were affected by the Opportunity NYC-Family Rewards program, a comprehensive conditional cash transfer program. The three-year program, launched by the Center for Economic Opportunity in the Mayor’s Office of the City of New York in 2007, offered cash assistance to low-income families to reduce economic hardship. The cash incentives were tied to activities and outcomes in children’s education, family preventive health care, and parents’ employment, in the hopes of increasing families’ “human capital” and reducing their poverty in the long term. An evaluation by MDRC of the first two years of the Family Rewards program, published in 2010, found that it had positive effects on families’ economic well-being and mixed effects on children’s education, family health care, and parents’ employment. For example, while the program did not affect school outcomes for younger children, it substantially boosted the achievement of a subset of older children who were better prepared for high school when they entered the program in the ninth grade. How the program affected teenagers and their parents is the focus of this study, which has been embedded in MDRCs continuing core evaluation of the program. This report addresses key “pathways” that may underlie any effects of the program on teenagers (such as changes in the way teenagers spent their time) as well as outcomes that were not targeted but that the program may have affected (such as teenagers’ mental health, aggressive behavior, or substance use.)
Genetic variation in dopamine pathways differentially associated with smoking progression in adolescence.

OBJECTIVE To clarify the nature of the association between dopamine genes and smoking by examining whether genetic variability in components of the dopamine pathway could explain refined phenotypes in adolescent smoking progression. METHOD Data are from an ongoing prospective study of the long-term outcome of early risk factors studied since birth. At age 15 years, 220 participants (108 males, 112 females) completed a self-report questionnaire measuring smoking behavior and were genotyped for five dopamine gene variants. RESULTS Smoking initiation was related to allelic variation in the dopamine D4 receptor gene (DRD4), whereas smoking continuation and dependence showed association with the dopamine D2 receptor gene (DRD2). Adolescents with the seven-repeat allele of the common DRD4 exon 3 polymorphism had rates of ever smoking that were significantly higher than in those with other genotypes. Once smoking started, carriers of the T allele of a single nucleotide polymorphism of DRD2 (rs4648317) reported higher rates of current smoking and scored higher on nicotine dependence than their allelic counterparts. Among current smokers, intention to quit was significantly lower in adolescents homozygous for the 10-repeat allele of the common dopamine transporter 3' untranslated region polymorphism. CONCLUSIONS Our results provide preliminary evidence of genetic influences on different stages of smoking and suggest the importance of specific dopamine genes in smoking progression in adolescence.
Competitive Interest Payments on Bank Deposits and the Long-Run Demand for Money: Reply

This paper tests two assumptions made in previous demand for money studies. The first assumption concerns the role assigned to "the" interest rate in the demand for money function. Common practice identifies the rate of interest with "the opportunity cost of holding money. " In Section I, this formulation is shown to blur an important distinction between "the price of money" and "the price of money substitutes" and to implicitly assume that the relevant price variable is the difference between these two distinct prices. A second assumption is that the current ban on interest payments on demand deposits is fully effective. In Section II, I operationally define these price variables and estimate perfectly competitive interest payments on commercial bank deposits. This is done by crudely measuring commercial bank marginal costs and assuming that all "excess" profit is passed on to depositors in indirect ways. Section III presents estimates of a more complete longrun demand for money relationship which explicitly includes an own price and a cross price as separate influences, and assumes that the prohibition of the payment of interest on deposits is totally ineffective. Although no firm conclusion is reached concerning the proper functional specification of the demand function, the results significantly improve upon previous demand for money estimates which assumed that the interest payment prohibition is totally effective. In Section IV, the results are summarized and implications of the analysis for monetary theory are presented. My competitive demand for money formulation leads to a reinterpretation of the existing evidence on what is generally referred to as "the interest elasticity of demand for money. " This estimate is shown to be significantly biased downward. It also implies that the demand for and supply of money are more interdependent than is usually assumed.
Analytical modelling of shipping business processes based on MCDM methods

The need for analytical solutions towards various managerial processes in shipping business has been clearly seen in maritime society. To remedy this gap, the execution of relevant processes can be supported via multiple criteria decision-making (MCDM) techniques. This article applied an Integrated Decision Aid (IDEA) to overcome the model selection dilemma for process improvement in shipping business. The illustrative application of the IDEA makes invaluable contributions for the ongoing efforts of relevant executives on adopting modern management style in shipping business. Furthermore, the outcomes of this study encourage the maritime practitioners towards analytical modelling of managerial processes in shipping business cycle.
Augmented virtual environment: fusion of real-time video and 3D models in the digital earth system

ABSTRACT An Augmented virtual environment (AVE) is concerned with the fusion of real-time video with 3D models or scenes so as to augment the virtual environment. In this paper, a new approach to establish an AVE with a wide field of view is proposed, including real-time video projection, multiple video texture fusion and 3D visualization of moving objects. A new diagonally weighted algorithm is proposed to smooth the apparent gaps within the overlapping area between the two adjacent videos. A visualization method for the location and trajectory of a moving virtual object is proposed to display the moving object and its trajectory in the 3D virtual environment. The experimental results showed that the proposed set of algorithms are able to fuse multiple real-time videos with 3D models efficiently, and the experiment runs a 3D scene containing two million triangles and six real-time videos at around 55 frames per second on a laptop with 1GB of graphics card memory. In addition, a realistic AVE with a wide field of view was created based on the Digital Earth Science Platform by fusing three videos with a complex indoor virtual scene, visualizing a moving object and drawing its trajectory in the real time.