Miracle-dz/UniFAR-FTUs huggingface dataset:
Nicotinic acetylcholine receptors mediate donepezil‐induced oligodendrocyte differentiation

Oligodendrocytes are the myelin‐forming cells of the central nervous system (CNS). Failure of myelin development and oligodendrocyte loss results in serious human disorders, including multiple sclerosis. Here, we show that donepezil, an acetlycholinesterase inhibitor developed for the treatment of Alzheimer's disease, can stimulate oligodendrocyte differentiation and maturation of neural stem cell‐derived oligodendrocyte progenitor cells without affecting proliferation or cell viability. Transcripts for essential myelin‐associated genes, such as PLP, MAG, MBP, CNPase, and MOG, in addition to transcription factors that regulate oligodendrocyte differentiation and myelination, were rapidly increased after treatment with donepezil. Furthermore, luciferase assays confirmed that both MAG and MBP promoters display increased activity upon donepezil‐induced oligodendrocytes differentiation, suggesting that donepezil increases myelin gene expression mainly through enhanced transcription. We also found that the increase in the number of oligodendrocytes observed following donepezil treatment was significantly inhibited by the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine, but not by the muscarinic acetylcholine receptor antagonist scopolamine. Moreover, donepezil‐induced myelin‐related gene expression was suppressed by mecamylamine at both the mRNA and protein level. These results suggest that donepezil stimulates oligodendrocyte differentiation and myelin‐related gene expression via nAChRs in neural stem cell‐derived oligodendrocyte progenitor cells.
Determinants of Intuitive Decision Making in Management: The Moderating Role of Affect

In this chapter, we propose a model of managerial intuitive decision making based on problem characteristics, decision characteristics, environmental factors, and individual factors. We propose also that affect moderates the intuitive decision-making process. Based on the affect infusion model (AIM), we suggest three interaction scenarios between the determinants of intuitive decision making and affect: moderate mood, high-intensity emotions, and affective feelings. We theorize that positive mood encourages the use of intuition while negative mood discourages it. We argue further that high-intensity emotions serve as a conduit to intuitive processing, but only if the decision maker focuses on the decision outcome. Conversely, we propose that high-intensity emotions can act as a barrier to intuition if the decision maker focuses on the emotion itself. Lastly, we hypothesize that managers will be more likely to use intuition in subsequent decisions if they receive affective confirmation as a result of their earlier use of intuitive decision making.
The Impact of Service Complexity on New Service Development – A Contingency Approach

This dissertation explores the limitations and impact on performance of applying formalised NPD processes in service innovation. Hypotheses build on a structural framework of organisational factors, which have been linked to successful product innovation but have not been consistently supported in a service context. Evidence is presented for a moderating influence of service complexity on the relationship between factors relating to NSD process organisation and new service performance. The findings create a link between product and service innovation and demonstrate that whereas complex new services benefit from formalised development processes and structure, services with lower complexity do not.
Mental Health Needs of Arab Women

Researchers indicate that the prevalence of psychiatric morbidity in the Arab region is similar to that found in other parts of the world. Women, in particular, are more likely to suffer various disorders including depression, anxiety disorders, somatization, and eating disorders. In this article, the author highlights some of the research on the mental health needs of Arab women. Consideration is given to important cultural and contextual factors related to mental illness as well as potential risk factors. Finally, suggestions for future directions are provided in order to attempt to close the gap between the needs and the services available.
Endocytic Profiles of d-Opioid Receptor Ligands Determine the Duration of Rapid but Not Sustained cAMP Responses s

Traditional assays that monitor cAMP inhibition by opioid receptor ligands require second-messenger accumulation over periods of 10–20 minutes. Since receptor regulation occurs within a similar time frame, such assays do not discriminate the actual signal from its modulation. Here we used bioluminescence resonance energy transfer to monitor inhibition of cAMP production by d-opioid receptor (DOR) agonists in real time. cAMP inhibition elicited by different agonists over a period of 15 minutes was biphasic, with response buildup during the first 6 to 7 minutes, followed by a second phase of response decay or of no further increment. The rate at which the cAMP response disappeared was correlated with operational parameters describing ligand efficiency [log(t/KA)] to promote Gai activation, as well as with ligand ability to promote internalization during the time course of the assay. Thus, ligands that displayed low signaling efficiency and poor sequestration (SB235863 ([8R-(4bS*,8aa,8ab,12bb)]7,10-dimethyl-1-methoxy11-(2-ethylpropyl)oxycarbonyl 5,6,7,8,12,12b-hexahydro-(9H)-4,8methanobenzofuro[3,2-e]pyrrolo[2,3-g]isoquinoline hydrochloride), morphine) had minimal or no response decay. On the other hand, the decay rate was pronounced for deltorphin II, [D-Pen(2), D-pen (5)]-enkephalin, met-enkephalin, and SNC-80 ((1)-4-[(aR)-a-((2S,5R)4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide), which displayed high signaling efficiency and internalization. Moreover, inhibition of internalization by dynasore reduced or abolished response decay by internalizing ligands. Unlike acute responses, endocytic profiles were not predictive of whether an agonist would induce prolonged cAMP inhibition over sustained (30–120 minutes) DOR stimulation. Taken together, the data indicate that ligand ability to evoke Gprotein activation or promote endocytosis was predictive of response duration over short, but not over sustained periods of cAMP inhibition.
Effectiveness of integrated multidisciplinary rehabilitation in primary brain cancer survivors in an Australian community cohort: a controlled clinical trial.

OBJECTIVE To evaluate effectiveness of a multidisciplinary rehabilitation program for persons following definitive primary brain tumour treatment in a community cohort. METHODS The brain tumour (glioma) survivors (n = 106) were allocated either to the treatment group (n = 53) (intensive ambulatory multidisciplinary rehabilitation), or the waitlist control group (n = 53). The primary outcome - Functional Independence Measure (FIM), measured 'Activity' limitation; secondary measures included Depression, Anxiety Stress Scale, Perceived Impact Problem Profile and Cancer Rehabilitation Evaluation System. Assessments were at baseline, 3 and 6 months after program completion. RESULTS Participants were predominantly women (56%), with mean age 51 years (standard deviation 13.6) and median time since diagnosis of 2.1 years. Intention-to-treat analysis showed a significant difference between groups at 3-month in favour of multidisciplinary rehabilitation program in FIM motor subscales: 'self-care', 'sphincter', 'locomotion', 'mobility'(p < 0.01 for all); and FIM 'communication' (p < 0.01) and 'psychosocial' subscales (p < 0.05), with small to moderate effect size (r = 0.2-0.4). At 6-month follow-up, significant improvement in the treatment group was maintained only for FIM 'sphincter', 'communication' and 'cognition' subscales (p < 0.01 for all). No difference between groups was noted in other subscales. CONCLUSIONS brain tumour survivors can improve function with multidisciplinary rehabilitation, with some gains maintained up to 6 months. Evidence for specific interventions in the 'blackbox' of rehabilitation is needed.
Retracted: Exendin‐4 reverts behavioural and neurochemical dysfunction in a pre‐motor rodent model of Parkinson's disease with noradrenergic deficit

BACKGROUND AND PURPOSE Parkinson's disease (PD) is characterized by progressive dopaminergic cell loss; however, the noradrenergic system exhibits degeneration as well. Noradrenergic deficit in PD may be responsible for certain non‐motor symptoms of the pathology, including psychiatric disorders and cognitive decline. The aim of this study was to generate a pre‐motor rodent model of PD with noradrenergic denervation, and to assess whether treatment with exendin‐4 (EX‐4), a glucagon‐like peptide 1 receptor agonist, could reverse impairment exhibited by our model.
Increased release of matrix components from articular cartilage in experimental canine osteoarthritis

The release rates of specific components of the proteoglycan aggregates (G1 domain, the chondroitin sulfate and keratan sulfate containing portion of the protein core, and link protein) of the articular cartilage of mature beagles were studied at early stages of canine experimental osteoarthritis (OA), generated by transection of the anterior cruciate ligament. Analysis of cartilage explants and synovial fluids indicates that at early stages of experimental OA, there is increased release of the proteoglycan aggregates of the articular cartilage. This involves a release from the tissue of the components of the proteoglycan that are specifically involved with aggregation together with the glycosaminoglycans of the proteoglycan. These components were detected at elevated levels in the media of explants of cartilage from the operated joint, and in the synovial fluids of the operated joints.
Green Advertising and Environmentally Responsible Consumer Behavior: The Level of Awareness and Perception of Malaysian Youth

The study determines to find the level of awareness and perception on green living amongst Malaysian youth through the use of advertising. The main objective is to explore awareness and perception of Malaysian youth towards green advertising promoted by the government. A survey was conducted to gather responses from online respondents using the social media website. Three hundred and twenty respondents have responded to the six month survey time, to a 20 questions questionnaire. The result indicates that, generally, the Malaysian youth have some awareness on what the term ‘green living’ denotes. However, those who practice green living are lower. They have been exposed to green advertising, but not all practice green living due to the lack of comprehensive understanding of the concept. The Malaysian youth exhibit positive perception towards green advertising. The finding concludes that there is a need for current and upcoming green advertising, especially ones that are done by the government to improve on their message delivery, creativity and information for the youth to respond in practice.
The joint impact of commitment to disclosure and prior forecast accuracy on managers' forecasting credibility

Managers list being viewed as committed disclosers as an important consideration in their voluntary disclosure decisions. Yet, prior research pays limited attention to how investors view commitment to disclosure. This study tests competing perspectives about how managers’ commitment to disclosure and prior forecast accuracy jointly influence managers’ forecasting credibility. One perspective (the information economics perspective) suggests that managers’ credibility is increasing in commitment to disclosure and prior forecast accuracy. A competing perspective (the omission bias perspective) suggests that the influence of commitment to disclosure on managers’ credibility depends on managers’ prior forecast accuracy. Experimental participants in the role of investors rate more (less) committed managers as more (less) credible, but only when managers are accurate. When managers are inaccurate, however, this relationship reverses. These results suggest that although managers’ concerns about commitment to disclosure are valid, when managers are less accurate, commitment to disclosure hurts, rather than helps their credibility.
Apoptosis in gliomas, and its role in their current and future treatment.

Apoptosis has recently entered the spotlight in the continuing search for new therapeutic approaches to cancer because it plays a twofold role in this disease. As stated by Lowe and Lin: "(M)ost cytotoxic anticancer agents induce apoptosis. (and so) the same mutations that suppress apoptosis during tumor development also reduce treatment sensitivity" (1). Therefore, any strategy aimed at increasing the propensity of glioma cells to undergo apoptosis could be therapeutic in its own right, but has the added potential of enhancing their sensitivity to other, established, treatments. As a corollary, understanding apoptotic mechanisms at the molecular level will not only help to explain why gliomas arise, but also identify points of intervention. This review will focus on these points, with emphasis on two families of apoptotic molecules, death ligands and their receptors, and BCL-2 family proteins. Near-term strategies of how apoptosis can be exploited therapeutically are discussed.
Inter- and Intra-Firm Linkages: Evidence from Microgeographic Location Patterns

Multiunit firms can draw on internal resources, thus their plants should depend less on external agglomeration benefits than comparable standalone plants. Because interacting at a distance is costly, multiunit firms should also be geographically 'compact'. We dissect the microgeographic location patterns of hundreds of thousands of Canadian establishments and find robust evidence for these predictions: multiunit firms are compact, and their plants locate in areas offering potentially less external agglomeration benefits. Within firms, plants with stronger vertical links are geographically more central. The latter effect is stronger for plants in high transport cost industries that produce durables and source a larger share of non-homogeneous inputs. These findings suggest that vertical supply chains are important in explaining firms' internal spatial organization.
Looking good by doing good: The antecedents and consequences of stakeholder attention to corporate disaster relief

type="main" xml:id="smj2246-abs-0001"> Stakeholder theory suggests a relationship between corporate social responsibility (CSR) and corporate financial performance (CFP) because certain stakeholders reward certain types of CSR. This argument assumes that stakeholders attend to firms' CSR activities—an assumption that has yet to be examined. We fill this gap by extending stakeholder theory to the context of stakeholder attention to firm CSR and exploring the antecedents and consequences of stakeholder attention to corporate disaster relief CSR. We test the resulting hypotheses on a sample of public companies that engaged in natural disaster relief efforts, finding that stakeholder attention partially mediated the relationship between disaster relief and CFP and that stakeholder attention to corporate disaster relief was driven by the legitimacy, urgency, and enactment of disaster relief CSR initiatives. Copyright © 2014 John Wiley & Sons, Ltd.
Information Cascades among Investors in Equity Crowdfunding

Finance studies on information cascades, usually in an initial public offering setting, typically differentiate between institutional and retail investors, as this is the only information available to potential backers. Information available through equity crowdfunding platforms includes details on individual investors as they may disclose information about themselves by linking their profile to social networks or websites. Using a sample of 132 equity offerings on Crowdcube in 2014, we show that information cascades among individual investors play a crucial role in crowdfunding campaigns. Investors with a public profile increase the appeal of the offer among early investors, who in turn attract late investors.
Metal-free molecular junctions on ITO via amino-silane binding—towards optoelectronic molecular junctions

Light control over currents in molecular junctions is desirable as a non-contact input with high spectral and spatial resolution provided by the photonic input and the molecular electronics element, respectively. Expanding the study of molecular junctions to non-metallic transparent substrates, such as indium tin oxide (ITO), is vital for the observation of molecular optoelectronic effects. Non-metallic electrodes are expected to decrease the probability of quenching of molecular photo-excited states, light-induced plasmonic effects, or significant electrode expansion under visible light. We have developed micron-sized, metal free, optically addressable ITO molecular junctions with a conductive polymer serving as the counter-electrode. The electrical transport was shown to be dominated by the nature of the self-assembled monolayer (SAM). The use of amino-silane (APTMS) as the chemical binding scheme to ITO was found to be significant in determining the transport properties of the junctions. APTMS allows high junction yields and the formation of dense molecular layers preventing electrical short. However, polar amino-silane binding to the ITO significantly decreased the conductance compared to thiol-bound SAMs, and caused tilted geometry and disorder in the molecular layer. As the effect of the molecular structure on transport properties is clearly observed in our junctions, such metal-free junctions are suitable for characterizing the optoelectronic properties of molecular junctions.
Reduced exposure might increase allergic sensitisation

EDITOR,—Pamela W Ewan makes the important statement that the incidence of peanut and nut allergy is rising and that sensitisation seems to occur early in life.1 Regrettably, she does not provide any evidence to back her recommendation that “young allergic children should avoid peanuts and nuts to prevent the development of this allergy” and her extraordinary suggestion …
Detection of Proton Movement Directly across Viral Membranes To Identify Novel Influenza Virus M2 Inhibitors

ABSTRACT The influenza virus M2 protein is a well-validated yet underexploited proton-selective ion channel essential for influenza virus infectivity. Because M2 is a toxic viral ion channel, existing M2 inhibitors have been discovered through live virus inhibition or medicinal chemistry rather than M2-targeted high-throughput screening (HTS), and direct measurement of its activity has been limited to live cells or reconstituted lipid bilayers. Here, we describe a cell-free ion channel assay in which M2 ion channels are incorporated into virus-like particles (VLPs) and proton conductance is measured directly across the viral lipid bilayer, detecting changes in membrane potential, ion permeability, and ion channel function. Using this approach in high-throughput screening of over 100,000 compounds, we identified 19 M2-specific inhibitors, including two novel chemical scaffolds that inhibit both M2 function and influenza virus infectivity. Counterscreening for nonspecific disruption of viral bilayer ion permeability also identified a broad-spectrum antiviral compound that acts by disrupting the integrity of the viral membrane. In addition to its application to M2 and potentially other ion channels, this technology enables direct measurement of the electrochemical and biophysical characteristics of viral membranes.
Conserved Polar Residues in Transmembrane Domains V, VI, and VII of Free Fatty Acid Receptor 2 and Free Fatty Acid Receptor 3 Are Required for the Binding and Function of Short Chain Fatty Acids*

FFA2 and FFA3 are closely related G protein-coupled receptors that bind and respond to short chain fatty acids. (FFA2 and FFA3 are the provisional International Union of Pharmacology designations for the receptors previously called GPR43 and GPR41, respectively.) Sequence comparisons between these two receptors and alignments with the related G protein-coupled receptor FFA1, linked to homology modeling based on the atomic level structure of bovine rhodopsin, indicated the potential for polar residues within the transmembrane helix bundle to play important roles in ligand recognition and function. In both FFA2 and FFA3, mutation of either an arginine at the top of transmembrane domain V or a second arginine at the top of transmembrane domain VII eliminated the function of a range of short chain fatty acids. Mutation of a histidine in transmembrane domain VI, predicted to be in proximity to both the arginine residues, also eliminated function in many but not all assay formats. By contrast, mutation of a histidine in transmembrane domain IV, predicted to be lower in the binding pocket, modulated function in some assays of FFA3 function but had limited effects on the function of acetate and propionate at FFA2. Interestingly, wild type FFA3 responded to caproate, whereas FFA2 did not. Mutation of the transmembrane domain IV histidine eliminated responses of FFA3 to caproate but resulted in a gain of function of FFA2 to this six-carbon fatty acid. These data demonstrate the importance of positively charged residues in the recognition and/or function of short chain fatty acids in both FFA2 and FFA3. The development of small molecule ligands that interact selectively with these receptors will allow further details of the binding pockets to be elucidated.
Botryoid rhabdomyosarcoma of the gallbladder in a child

The first case of botryoid rhabdomyosarcoma of the gallbladder in a child is described and compared with previously reported cases from the world literature. Despite its rarity, rhabdomyosarcoma of the liver and biliary system should be considered when an obstructive jaundice is seen in children. Radical surgery with additional chemotherapy and radiotherapy are necessary for long‐term survival.
How to Stay in The Market? - Products and Process Innovation as a Response to Increasing Imports and Foreign Direct Investment

The paper analyses the effects of imports and inward foreign direct investment (FDI) on the innovative activity of domestic firms. The effects are assumed to be positive, since imports and FDI increase the competition on domestic markets and domestic firms have to perform more efficiently to maintain their market position. The hypothesis is tested on the basis of a panel data set containing 1270 firms of the German manufacturing industry over the period from 1984 to 1989. For the econometric estimation two different approaches are applied and compared: the pooled probit estimator with time-varying intercepts and Chamberlain’s random effects probit. The latter accounts for unobserved heterogeneity depending on exogenous variables and allows for a flexible covariance structure of the error term. It is found that both import share and FDI-share have positive significant effects on product and process innovation, but they seem to play a more important role as a determinant of product innovation. J.E. L. -classification: 229, 621