Miracle-dz/UniFAR-FTUs huggingface dataset:
Niche-derived laminin-511 promotes midbrain dopaminergic neuron survival and differentiation through YAP

Activation of the transcription factor YAP by an extracellular laminin promotes the differentiation and survival of dopaminergic neurons. YAP supports dopaminergic neurons Parkinson’s disease (PD) is a neurodegenerative disorder marked by progressive loss of dopaminergic neurons and motor control. Various factors promote or inhibit neuronal survival. Zhang et al. found that a prosurvival signal was mediated by the transcription cofactor YAP. YAP was activated in midbrain dopaminergic neurons in culture and in mice through an interaction between an integrin and the extracellular matrix protein laminin-511. YAP then transcriptionally activated dopaminergic neuron differentiation factors and a microRNA that decreased the synthesis of the apoptotic protein PTEN. The findings uncover a new role for YAP in neurons and a pathway that might be explored for the purpose of promoting dopaminergic neuron survival in PD patients. Parkinson’s disease (PD) is a neurodegenerative disorder in which the loss of dopaminergic neurons in the midbrain (mDA neurons) causes progressive loss of motor control and function. Using embryonic and mDA neurons, midbrain tissue from mice, and differentiated human neural stem cells, we investigated the mechanisms controlling the survival of mDA neurons. We found that the extracellular matrix protein laminin-511 (LM511) promoted the survival and differentiation of mDA neurons. LM511 bound to integrin α3β1 and activated the transcriptional cofactor YAP. LM511-YAP signaling enhanced cell survival by inducing the expression of the microRNA miR-130a, which suppressed the synthesis of the cell death–associated protein PTEN. In addition, LM511-YAP signaling increased the expression of transcription factors critical for mDA identity, such as LMX1A and PITX3, and prevented the loss of mDA neurons in response to oxidative stress, a finding that warrants further investigation to assess therapeutic potential for PD patients. We propose that by enhancing LM511-YAP signaling, it may be possible to prevent mDA neuron degeneration in PD or enhance the survival of mDA neurons in cell replacement therapies.
Focal surface displays

Conventional binocular head-mounted displays (HMDs) vary the stimulus to vergence with the information in the picture, while the stimulus to accommodation remains fixed at the apparent distance of the display, as created by the viewing optics. Sustained vergence-accommodation conflict (VAC) has been associated with visual discomfort, motivating numerous proposals for delivering near-correct accommodation cues. We introduce focal surface displays to meet this challenge, augmenting conventional HMDs with a phase-only spatial light modulator (SLM) placed between the display screen and viewing optics. This SLM acts as a dynamic freeform lens, shaping synthesized focal surfaces to conform to the virtual scene geometry. We introduce a framework to decompose target focal stacks and depth maps into one or more pairs of piecewise smooth focal surfaces and underlying display images. We build on recent developments in "optimized blending" to implement a multifocal display that allows the accurate depiction of occluding, semi-transparent, and reflective objects. Practical benefits over prior accommodation-supporting HMDs are demonstrated using a binocular focal surface display employing a liquid crystal on silicon (LCOS) phase SLM and an organic light-emitting diode (OLED) display.
Correctors Rescue CFTR Mutations in Nucleotide‐Binding Domain 1 (NBD1) by Modulating Proteostasis

We evaluated whether small molecule correctors could rescue four nucleotide‐binding domain 1 (NBD1) mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (A455E, S492F, ΔI507, and R560T). We first transfected Cos‐7 cells (green monkey kidney cells) with A455E, S492F, ΔI507, or R560T and created HEK‐293 (human embryonic kidney cells) cell lines stably expressing these CFTR mutations. The mutants showed lowered protein expression, instability at physiological temperature, and rapid degradation. After treatment with correctors CFFT‐002, CFFT‐003, C3, C4, and/or C18, the combination of C18+C4 showed the most correction and resulted in increased CFTR residing in the plasma membrane. We found a profound decrease in binding of CFTR to histone deacetylases (HDAC) 6 and 7 and heat shock proteins (Hsps) 27 and 40. Silencing Hsp27 or 40 rescued the mutants, but no additional amount of CFTR was rescued when both proteins were knocked down simultaneously. Thus, CFTR mutations in NBD1 can be rescued by a combination of correctors, and the treatment alters the interaction between mutated CFTR and the endoplasmic reticulum machinery.
Religion, Corporate Governance, and Executive Compensation

We investigate how regional variation in religiosity and the prevalent religious denomination in a U.S. state where a company is headquartered are associated with the level and structure of executive compensation. We document a substantial compensation premium in executives working at firms headquartered in U.S. states with a high proportion of Catholics and conversely a discount in states with a high proportion of Protestants. We provide evidence suggesting that these findings are not caused by heterogeneous demand for executives’ effort, managerial ability, or social skills. Our results are consistent with the “Catholic premium” and the “Protestant discount” being associated with the adherence to different social values that have implications for corporate governance quality and for managerial entrenchment. Our results highlight the importance of social values for economic activity and for contracting between economic agents.
Nasal embryonic LHRH factor plays a role in the developmental migration and projection of gonadotropin‐releasing hormone 3 neurons in zebrafish

The initiation of puberty and the functioning of the reproductive system depend on proper development of the hypophysiotropic gonadotropin‐releasing hormone (GnRH) system. One critical step in this process is the embryonic migration of GnRH neurons from the olfactory area to the hypothalamus. Using a transgenic zebrafish model, Tg(gnrh3:EGFP), in which GnRH3 neurons and axons are fluorescently labeled, we investigated whether zebrafish NELF is essential for the development of GnRH3 neurons. The zebrafish nelf cDNA was cloned and characterized. During embryonic development, nelf is expressed in GnRH3 neurons and in target sites of GnRH3 projections and perikarya, before the initiation of their migration. Nelf knockdown resulted in a disruption of the GnRH3 system which included absence or misguiding of GnRH3 axonal outgrowth and incorrect or arrested migration of GnRH3 perikarya. These results suggest that Nelf is an important factor in the developmental migration and projection of GnRH3 neurons in zebrafish. Developmental Dynamics 238:66–75, 2009. © 2008 Wiley‐Liss, Inc.
Haemophilia care in Europe: a survey of 19 countries

Summary. In 2009, a questionnaire was circulated to 19 national haemophilia patient organizations in Europe affiliated to the European Haemophilia Consortium (EHC) and the World Federation of Hemophilia (WFH) to seek information about the organization of haemophilia care and treatment available at a national level. The responses received highlighted differences in the level of care despite the recent promulgation of consensus guidelines designed to standardize the care of haemophilia throughout the continent of Europe. There was a wide range in factor VIII consumption with usage ranging from 0.38 IU per capita in Romania to 8.7 IU per capita in Sweden (median: 3.6 IU per capita). Despite the specific inclusion of coagulation factor concentrate in the WHO list of essential medications, cryoprecipitate is still used in some eastern European countries.
IL-4 Inhibits Bone-Resorbing Activity of Mature Osteoclasts by Affecting NF-κB and Ca2+ Signaling1

IL-4 is an important immune cytokine that regulates bone homeostasis. We investigated the molecular mechanism of IL-4 action on bone-resorbing mature osteoclasts. Using a highly purified population of mature osteoclasts, we show that IL-4 dose-dependently inhibits receptor activator of NF-κB ligand (RANKL)-induced bone resorption by mature osteoclasts. We detected the existence of IL-4R mRNA in mature osteoclasts. IL-4 decreases TRAP expression without affecting multinuclearity of osteoclasts, and inhibits actin ring formation and migration of osteoclasts. Interestingly, IL-4 inhibition of bone resorption occurs through prevention of RANKL-induced nuclear translocation of p65 NF-κB subunit, and intracellular Ca2+ changes. Moreover, IL-4 rapidly decreases RANKL-stimulated ionized Ca2+ levels in the blood, and mature osteoclasts in IL-4 knockout mice are sensitive to RANKL action to induce bone resorption and hypercalcemia. Furthermore, IL-4 inhibits bone resorption and actin ring formation by human mature osteoclasts. Thus, we reveal that IL-4 acts directly on mature osteoclasts and inhibits bone resorption by inhibiting NF-κB and Ca2+ signaling.
Determination of carbonyl functions in cellulosic substrates

The reliable and accurate determination of oxidized functionalities in cellulosic substrates still represents a largely unsolved problem in cellulose chemistry. Aldehyde and keto structures are “hot spots” along the cellulose chain, where further chain cleavage might occur. Carbonyls are also relevant for processes such as yellowing or aging. Conventional approaches (copper number, oxime or cyanohydrin method) provide sum parameters only and suffer from limited comparability. In our approach fluorescence labeling was chosen. Pulps are treated with a highly selective fluorescence label and are subsequently analyzed by size exclusion chromatography. The method is applied as pre-column derivatization and allows the measurement of carbonyl profiles (plots DS vs. MW). Thus, the total carbonyl content and the differential mass distribution of pulps can be determined. Practical aspects of the newly developed method, a comparison of the approach to conventional methods, and different applications demonstrating the general scope of the method will be presented.
Avantajele competitive ale României pe piaţa internă a UE

This study contributes to the literature on the competitiveness of Romanian exports with a new perspective over the decade 2001-2011, by overlapping of two complementary analyses: of the export performance dynamics and of the domestic revenues created by export manufacturers and their suppliers. The analyzed period includes the period of global economic growth (mainly 2003-2007) and the first years of the economic crisis (2009-2011 ). The year 2007, when Romania joined the European Union, is in the middle of the analyzed period. The dynamics of Romania's export performance was assessed through a specific method combining three different research lines(1) changes in the ranking of exported products in the reference years 2001 and 2011, (2) evolution of the performance of key products exported in 2001 and (3) the position in 2001 of key products exported in 2011. The analysis of domestic revenues created by export manufacturers and their suppliers provides, for the first time for Romania a brief study on the position of the country on the global value chain, following the logic proposed by the European Commission in its last two European Competitiveness Reports (2012 and 2013). When corroborated, the results of the two analyses can be used to discuss the extent to which the current structure of exports contributes to the generation of domestic revenues and as such might prove useful in the debate on the identification of a country brand for Romania. In order to achieve the latter goal, we conducted two detailed case studies on two reference sectors of the Romanian economy: motor vehicles and creative industries. [. ]
Intellectual Capital Management: Pathways to Sustainable Competitive Advantage

Managing intellectual capital has gained popularity among both academia and industry setting due to numerous firms’ attempts to gain a sustainable competitive advantage. In order to improve the ability of financial statements to offer an adequate picture of the firm’s financial position, it will be necessary to capture a wide range of intangible determinants such as knowledge, innovation and intellectual property that are seen as the vital determinants of firms’ success. The literature presents a series of intellectual capital management models that illustrate the various facets a firm must consider when managing intellectual capital. Then, the component of elements of intellectual capital are also identified, defined and discussed at different stages of knowledge development to fit better with the theory. Only when intellectual capital management is present, the intellectual capital components of the organisation can be tapped effectively. Though it is acknowledged that intellectual capital management promotes sustainable competitive advantage, intellectual capital management in Asian countries including Malaysia is not as rigorous as countries in the West. Therefore, the aim of this paper is to explore the CICM model for Malaysian firms that will improve the existing models. By employing the model, it is expected that there is a relationship between intellectual capital management and sustainable competitive advantage of Malaysian firms.
Reduction of leucocyte telomere length in radiographic hand osteoarthritis: a population-based study

Background: Although age is the strongest predictor of osteoarthritis, the exact mechanism underlying this disorder remains elusive. Objective: To examine the association between leucocyte telomere length (LTL), a bio-indicator of ageing, and radiographic hand osteoarthritis. Methods: An unselected, predominantly female sample from the TwinsUK Adult Twin Registry (Twin Research and Genetic Epidemiology Unit, St Thomas Hospital, London, UK) was studied. Radiographs of both hands were obtained with a standard posteroanterior view and assessed for radiographic osteoarthritis according to the Kellgren/Lawrence (K/L) score. Individual radiographic features including osteophytes and joint space narrowing (JSN) were also assessed on a four-point scale using a standard atlas. Hand osteoarthritis was defined radiographically as having ⩾3 osteoarthritis-affected joints of both hands (K/L score⩾2). Severity of hand osteoarthritis was indicated semiquantitatively by total K/L scores, osteophytes, JSN scores and proportion of joints affected. Mean LTL was measured by the terminal restriction fragment length using the Southern blot. Results: A total of 1086 Caucasian subjects (mean (SD) age 55 (8.0) years) were studied. LTL was 6.95 (0.64) kb and was inversely correlated with age. After adjustment for age, sex, body mass index and smoking, LTL was significantly shorter by 178 bp in subjects with hand osteoarthritis (n = 160) than in those without (n = 926; p = 0.04). LTL was also significantly associated with semicontinuous measures of osteoarthritis (eg, total K/L score, JSN score, osteophyte score and proportion of joints affected) after adjustment (all p⩽0.02) in a dose–response fashion. Conclusion: Shorter LTL equivalent to around 11 years of annual loss in normal people is associated with radiographic hand osteoarthritis and disease severity, suggesting potential shared mechanisms between osteoarthritis and ageing, and implicating oxidative stress and low-level chronic inflammation in both conditions.
KAJIAN DAN STRATEGI PENDUKUNG PERKEMBANGAN E-COMMERCE BAGI UMKM DI INDONESIA

Menghadapi Asean Economic Community (AEC) yang telah dimulai pada tahun 2016, Usaha Mikro Kecil Menengah (UMKM) diharapkan semakin produktif dan berdaya saing. Salah satu cara untuk meningkatkan daya saing yaitu melalui adopsi ICT (information, communication and technology) termasuk adopsi e-commerce . Penelitian ini bertujuan untuk mengetahui kondisi eksisting, potensi e-commerce, mengetahui faktor pendukung dan penghambat adopsi e-commerce bagi UMKM serta merumuskan strategi pendukung perkembangan e-commerce bagi UMKM. Metode Penelitian menggunakan metode kualitatif deskriptif dengan pendekatan induktif. Faktor pendukung dan Penghambat serta strategi pendukung berdasarkan survei perilaku konsumen dan riset perkembangan adopsi e-commerce telah dipetakan dalam analisis SWOT kualitatif dan kuantitatif. Hal ini bermanfaat sebagai masukan bagi stakeholder khususnya pemerintah dan pelaku UMKM untuk memperkuat sektor UMKM terutama dalam hal peningkatan adopsi e-commerceKata Kunci: e-commerce, UMKM, strategi pendukung, Analisis SWOT
Business model experimentation for circularity: Driving sustainability in a large international clothing retailer

Business model experimentation for sustainability is an intentional and systematic ap-proach to identify, test and learn about value creation strategies that could be adopted by a business in response to current unsustainable trajectories. For businesses such as large clothing retailers the need to alter course is acute as pressure builds from economic, environmental and social angles. The circular economy concept provides a potential powerful lever for change. To date, however, scant research has been conducted on how circular business model experimentation is conducted. We present an indepth action research case study of a large international clothing retailer embarking on a journey of business model experimentation for circularity: the processes, methods, roles and the organisation in light of the need to address broad sustainability challenges in the business. It was found that experimentation activities oscillated between slow and loaded, and faster and un-weighted modes. While an intentional and stepwise process was sought, in reality it was largely emergent and highly iterative. Through this iterative process, new circular business models were generated that co-exist with current non-circular ones. Confidence in experimentation as a business capability also increased through this collaborative project. This study provides insights into how to conduct lean startup type business model experimentation for circularity in a large organisation. For practitioners, the benefits of academic-industry collaboration, and the oscillating dynamics of business model experimentation are illuminated.
Real-time Tracking of Motor Response Activation and Response Competition in a Stroop Task in Young Children: A Lateralized Readiness Potential Study

The ability to select an appropriate motor response by resolving competition among alternative responses plays a major role in cognitive performance. fMRI studies suggest that the development of this skill is related to the maturation of the frontal cortex that underlies the improvement of motor inhibition abilities. However, fMRI cannot characterize the temporal properties of motor response competition and motor activation in general. We studied the development of the time course of resolving motor response competition. To this end, we used the lateralized readiness potential (LRP), an ERP measure, for tracking correct and incorrect motor cortex activation in children in real time. Fourteen children and 14 adults took part in an animal-size Stroop task where they selected between two animals, presented simultaneously on the computer screen, which was larger in real life. In the incongruent condition, the LRP detected stronger and longer lasting incorrect response activation in children than in adults. LRP results could explain behavioral congruency effects, the generally longer RT in children than in adults and the larger congruency effect in children than in adults. In contrast, the peak latency of ERP waves, usually associated with stimulus processing speed, could explain neither of the above effects. We conclude that the development of resolving motor response competition, relying on motor inhibition skills, is a crucial factor in child development. Our study demonstrates that the LRP is an excellent tool for studying motor activation in children.
Contemporary financial reporting and intangible resources: Implications for corporate governance

The key question of this paper is what are the implications for corporate governance from the emergence of contemporary financial reporting and intangible resources? Going beyond traditional financial reporting, Boards of Directors and corporate executives should investigate the intangible resources of contemporary financial reporting. What intangible resources are causing the huge price to earnings (PE) ratio gap and the huge market to book (M/B) ratio gap for their companies? Possibly such gaps are driven by global brand names, global licensing, customer loyalty, product quality, and product innovation. Unfortunately, the short-term focus upon traditional financial reporting by both Wall Street and corporate executives to “make the numbers”, i.e. short-term (quarterly), predicted numbers, has damaged firms’ competitiveness. Such damages include postponing or cutting expenditures on emerging technologies, advertising, research and development, employee training, and maintenance expenses. Research has shown that such earnings management techniques are relatively futile efforts since a consensus earnings miss by a company generally produces an insignificant 1.5% to 2% share price drop. Boards of Directors should inform corporate executives accordingly. To offer solutions to these issues and implications for corporate governance, this paper is divided into the following sections: the emergence of contemporary financial reporting; asset value migration: the power of intangibles; top five future business value drivers: all intangibles; forward looking measures for intangible resources; market gaps: “old economy” versus “new economy” companies; global brands and global licensing; hidden intangible values made visible; international perspectives on contemporary financial reporting; and conclusions.
Phylogenetic comparison of retron elements among the myxobacteria: evidence for vertical inheritance

Twenty-eight myxobacterial strains, representing members from all three subgroups, were screened for the presence of retron elements, which are novel prokaryotic retroelements encoding reverse transcriptase. The presence of retrons was determined by assaying strains for a small satellite DNA produced by reverse transcription called multicopy, single-stranded DNA (msDNA). An msDNA-producing retron appeared to be absent from only one of the strains surveyed. DNA hybridization experiments revealed that retron elements similar to retron Mx162, first identified in Myxococcus xanthus, were found only among members of the Myxococcus subgroup; that is, each of the seven different genera which constitute this subgroup contained a Mx162 homolog. Another retron element also appeared to have a clustered distribution, being found exclusively within the Nannocystis subgroup of the myxobacteria. A retron element of the Mx162 type was cloned from Melittangium lichenicola, and its DNA sequence was compared with those of similar elements in M. xanthus and Stigmatella aurantiaca. Together, the degree of sequence diversity, the codon bias of the reverse transcriptase genes, and the clustered distribution of these retrons suggest a possible evolutionary scenario in which a common ancestor of the Myxococcus subgroup may have acquired this retroelement.