Miracle-dz/UniFAR-FTUs huggingface dataset:
Monoamine Oxidase-A Occupancy by Moclobemide and Phenelzine: Implications for the Development of Monoamine Oxidase Inhibitors

Background: Monoamine oxidase inhibitors (MAOIs) are being developed for major depressive disorder, Alzheimer’s, and Parkinson’s Disease. Newer MAOIs have minimal sensitivity to tyramine, but a key limitation for optimizing their development is that standards for in vivo monoamine oxidase-A (MAO-A) occupancy in humans are not well established. The objectives were to determine the dose-occupancy relationship of moclobemide and the occupancy of phenelzine at typical clinical dosing. Methods: Major depressive episode (MDE) subjects underwent [11C]harmine positron emission tomography scanning prior to and following 6 weeks of treatment with moclobemide or phenelzine. Results: Mean brain MAO-A occupancies were 74.23±8.32% for moclobemide at 300–600mg daily (n = 11), 83.75±5.52% for moclobemide at 900–1200mg daily (n = 9), and 86.82±6.89% for phenelzine at 45–60mg daily (n = 4). The regional dose-occupancy relationship of moclobemide fit a hyperbolic function [F(x) = a(x/[b + x]); F(1,18) = 5.57 to 13.32, p = 0.002 to 0.03, mean ‘a’: 88.62±2.38%, mean ‘b’: 69.88±4.36 mg]. Multivariate analyses of variance showed significantly greater occupancy of phenelzine (45–60mg) and higher-dose moclobemide (900–1200mg) compared to lower-dose moclobemide [300–600mg; F(7,16) = 3.94, p = 0.01]. Conclusions: These findings suggest that for first-line MDE treatment, daily moclobemide doses of 300–600mg correspond to a MAO-A occupancy of 74%, whereas for treatment-resistant MDE, either phenelzine or higher doses of moclobemide correspond to a MAO-A occupancy of at least 84%. Therefore, novel MAO inhibitor development should aim for similar thresholds. The findings provide a rationale in treatment algorithm design to raise moclobemide doses to inhibit more MAO-A sites, but suggest switching from high-dose moclobemide to phenelzine is best justified by binding to additional targets.
Social norms and self-presentation on social network sites: Profile work in action

“Profile work,” that is strategic self-presentation in social network sites, is configured by both the technical affordances and related social norms. In this article, we address technical and social psychological aspects that underlie acts of sharing by analyzing the social in relation to the technical. Our analysis is based on two complementary sets of qualitative data gleaned from in situ experiences of Finnish youth and young adults within the sharing mechanisms of Facebook and Last.fm. In our analysis, we identified social norms that were formed around the prevailing sharing practices in the two sites and compared them in relation to the sharing mechanisms. The analysis revealed that automated and manual sharing were sanctioned differently. We conclude that although the social norms that guide content sharing differed between the two contexts, there was an identical sociocultural goal in profile work: presentation of authenticity.
Rhododendron oldhamii leaf extract improves fatty liver syndrome by increasing lipid oxidation and decreasing the lipogenesis pathway in mice

Some members of Rhododendron genus are traditionally used as medicinal plants for arthritis, acute and chronic bronchitis, asthma, pain, inflammation, rheumatism, hypertension and metabolic diseases. To the best of our knowledge, there is no report on the protective effects of R. oldhamii leaf extract on non-alcoholic fatty liver disease (NAFLD) in vivo and in vitro. In this study, the effects of R. oldhamii leaf extract on inhibiting the free fatty acid (FFA)-induced accumulation of fat in HepG2 cells and on improving fatty liver syndrome in mice with high fat diet (HFD)-induced NAFLD were investigated. For the in vitro assay, HepG2 cells were treated with FFAs (oleate/palmitate = 2:1) with or without treatment with R. oldhamii leaf ethyl acetate (EtOAc) fraction to observe lipid accumulation using Nile red and oil red O stains. For the in vivo assay, C57BL/6 mice were randomly assigned to three groups (n = 5), including the normal diet group, the HFD group and the HFD+EtOAc group. After 11 weeks, body weight, serum biochemical indices and the mRNA expressions of the liver tissue, as well as the outward appearance, weight and histopathological analysis of liver and adipose tissues were evaluated. Among the fractions derived from R. oldhamii leaf, the EtOAc fraction exhibited a strong fat-accumulation inhibitory activity. Following reverse-phase high-performance liquid chromatography (HPLC), four specific phytochemicals, including (2R, 3R)-astilbin (AS), hyposide (HY), guaijaverin (GU) and quercitrin (QU), were isolated and identified from the EtOAc fraction of R. oldhamii leaf extract. Among them, AS and HY showed excellent fat-accumulation inhibitory activity. Thus, the EtOAc fraction of R. oldhamii leaf and its derived phytochemicals have great potential in preventing FFA-induced fat accumulation. In addition, the EtOAc fraction of R. oldhamii leaf significantly improved fatty liver syndrome and reduced total cholesterol (TC) and triglyceride (TG) in HFD-induced NAFLD mice at a dosage of 200 mg/kg BW. These results demonstrated that the methanolic extracts from R. oldhamii leaf have excellent inhibitory activities against fat accumulation and anti-NAFLD activities and thus have great potential as a natural health product.
UvA-DARE ( Digital Academic Repository ) High-mass X-ray binaries in the Magellanic clouds

We present a catalogue of high-mass X-ray binaries in the Magellanic Clouds. The catalogue lists source name(s), coordinates, apparent magnitudes, orbital parameters, and X-ray luminosity of 128 high-mass X-ray binaries, together with stellar parameters of the components, other characteristic properties and a comprehensive selection of the relevant literature. The aim of this catalogue is to provide easy access to the basic information on the X-ray sources and their counterparts in other wavelength ranges (UV, optical, IR, radio). Most of the sources are identified to be Be/X-ray binaries. Some sources, however, are only tentatively identified as high-mass X-ray binaries on the basis of a transient character and/or a hard X-ray spectrum. Further identification in other wavelength bands is needed to finally determine the nature of these sources. In cases where there is some doubt about the high-mass nature of the X-ray binary this is mentioned. Literature published before 1 May 2005 has, as far as possible, been taken into account.
Do Different Audit Report Formats Affect Shareholders' and Auditors' Perceptions?

This study investigates the impact of three different audit report formats on shareholders' and auditors' perceptions. The formats are derived from the Guidance Note Report to Australian Standard AUS702 which aims to improve communications between auditors and shareholders. Formats include an expanded report, a plain language expanded report with the audit opinion at the end, and a plain language expanded report with the audit opinion at the start. A questionnaire research instrument was mailed to shareholders and auditors. In general, the audit report formats did not reduce the expectations gap between shareholders and auditors. A greater number of significant differences between shareholders' and auditors' perceptions were evident for the expanded format (vis-a-vis the AUS 702 short format), while fewer significant differences existed for the plain language expanded report with the audit opinion at the start.
Does Trade Stimulate Product Quality Upgrading? (Est‐ce que le commerce international stimule l'amélioration de la qualité des produits)

This paper investigates whether increased import competition leads firms to engage in incremental innovation reflected in product quality upgrading using Chilean manufacturing firmproduct data and measuring product quality with unit values (prices). We identify causal effects of import competition using an effective trade barrier measure transport costs as instruments for import penetration ratios across industries. Transport costs have a negative and significant effect on product quality. The evidence suggests that estimated unit value increases capture product quality upgrading, imports competition effects drive quality upgrading, and benefits depend on firms industrial specialization. Easier access to intermediate inputs also fosters quality upgrading.
Student retention: Current evidence and insights for improvement

The Australian Government has set the ambitious target that 40 per cent of all 25 to 34 year olds will hold a qualification at bachelor level or above by 2025. Funding to increase the participation of persons from low socioeconomic status (SES) backgrounds is proposed as a key initiative for achieving the broader attainment goal. In order to meet the attainment goal, however, it will not only be essential to ensure that more students enter higher education, but that these students are able to successfully navigate through their courses, raising issues of retention and ultimately completion. As new enrolments are expected to come disproportionately from low SES backgrounds and other groups that are historically under-represented in the sector (Edwards, 2011), the performance of these groups after entering university will be crucial for the meeting of the attainment target. Previous Joining the Dots research briefings have focused on demand for higher education and enrolments. In this briefing, attention turns to how students who commence higher education studies progress through their courses. The briefing provides a synthesis of currently available information on student retention, attrition, and completions, as well as the reasons underlying course non-completion. The retention of students from low SES backgrounds, a group targeted in current Australian Government participation initiatives, will form the focus of the second half of the briefing.
Depletion of carbonic anhydrase IX abrogates hypoxia-induced overexpression of stanniocalcin-1 in triple negative breast cancer cells

ABSTRACT Carbonic anhydrase IX (CAIX) is a pH-regulating enzyme that plays a key role in maintaining an alkaline intracellular pH under hypoxic conditions. It is overexpressed in a variety of solid cancers, including breast cancer (BC), and has been implicated in the migration, invasion and stemness of breast cancer cells. Therefore, CAIX recently emerged as a novel therapeutic target for the treatment of BC. To gain an insight into the mechanism of action of CAIX inhibitors, we investigated the impact of CAIX knock-down on the transcriptional response to hypoxia in 2 BC cell lines – MCF7 and MDA-MB-231, by performing a global gene expression analysis. This showed that CAIX knock-down had a relatively minor effect on the global transcriptional response to hypoxia, however it blocked hypoxia-induced upregulation of stanniocalcin-1 (STC1), a secreted glycoprotein that has been shown to promote tumor progression and metastasis in BC. Kaplan-Meier survival analysis showed that high STC1 expression is significantly associated with poor survival in patients with basal-type breast cancer but not luminal A and HER2+ subtypes. Moreover, the association was particularly high in a subgroup of basal-type BC patients with TP53 mutations thus revealing a putative cooperation of STC1 with mutated TP53 in generating highly aggressive BC subgroup. Taken together, these findings show that CAIX inhibitors at least partially act through blocking STC1 induction in BC cells and reveal a subgroup of BC patients, who potentially would benefit most from the treatment with CAIX inhibitors.
The efficacy of principle‐based corporate governance practices and firm financial performance: An empirical investigation

Purpose - This paper seeks to address the effect that principle-based corporate governance practices have on the financial performance of large publicly-listed companies. In 2004, the New Zealand Securities Commission (NZSC) promulgated nine high level principles and guidelines for all business entities with an aim of improving corporate governance practices and boosting investor confidence in the New Zealand capital market. This event provides a point for empirically testing companies' responses. Design/methodology/approach - Panel data for the NZX top 50 companies over the period 1999-2007 are analysed using ordinary least squares (OLS) and two stage least squares (2SLS) regression techniques to evaluate whether: those firms that were continuously compliant with the NZSC requirements perform better; and the firm performance post-NZSC recommendations is better than pre-NZSC recommendations. Tobin's Findings - The findings indicate that large listed companies have universally adopted the Securities Commission recommendations, establishing subcommittees for audit and remuneration, and having a majority of non-executive/independent directors on the board which, on average, have seven members. There is support for the view that the NZSC recommendations have had positive influence on firm performance measured by Tobin's Research limitations/implications - This study provides empirical support for the corporate governance recommendations made by the NZSC in 2004, giving support to the principle-based corporate governance practices to be adopted in New Zealand. The sequential testing of each NZSC recommendation provides a comprehensive picture of performance outcomes which has not been achieved in prior research. The interdependency issues are of interest and the correlation between recommendations provides useful insights. Originality/value - This study offers insights for policy makers interested in adopting principle-based corporate governance practices within their country. Within New Zealand, public policy developments and stock exchange listing requirements/regulatory issues with associated compliance burdens are better informed as a consequence of the research.
We are not the same people we used to be: An exploration of family biographical narratives and identity change following traumatic brain injury

ABSTRACT Subjective changes are increasingly recognised as important in recovery and rehabilitation following traumatic brain injury. Accumulation of subjective changes over time has led many to examine the question of “continuity of self” post-injury. Vacillation between feeling the same and different is common and often at odds with the medical narrative preparing families for permanent change. This position of ambiguity was examined in a qualitative narrative study. The aim of this paper is to describe the narrative structures used by uninjured members of a family to understand change. These changes relate primarily, to their perspective of whether and how the injured person had changed, but also secondarily to whether and why they themselves felt they had changed in the first year post-injury. Nine uninjured family members from three families took part in three unstructured interviews during the first twelve months post-injury. In-depth narrative analysis showed family members used biographical attendance; biographical disruption; biographical continuity; and biographical reconstruction to understand change. Drawing on these findings it is argued that concentrating on a narrative of change is too limiting and that engaging in biographical narratives may help humanise care provided to injured individuals and their families. Implications for research and practice are discussed.
The Wounds of Exclusion: Poverty, Women’s Health, and Social Justice

In this insightful and informative book based on her doctoral dissertation, The Wounds of Exclusion: Poverty, Women’s Health, and Social Justice, Colleen Reid explores how a group of women living in poverty understand and define health and how they participate in forms of social justice in relation to women’s health. Winner of the 2002/2003 International Institute for Qualitative Methodology Dissertation Award, Reid also engages in an ongoing critique of the feminist action research model she adopted as a methodological framework for her study. Reid presents a solid interdisciplinary theoretical foundation for her research, drawing on health equity studies and feminist and social justice theories. Using a social determinants-of-health perspective (one that claims that health is influenced by social factors such as race, sex, income, and class), she argues that dominant discourses of health exclude people who live on the margins of society. She contends that people who live in poverty are less healthy than wealthier people, yet current health inequities research does not adequately investigate what causes the disparities. Moreover, it fails to address women’s health and issues of poverty. Hence Reid asked the following questions for her research.
Role of Potassium Channels in Amyloid‐Induced Cell Death

Abstract: Basal forebrain cholinergic neurons are severely depleted early in Alzheimer's disease and appear particularly susceptible to amyloid β‐peptide (Aβ) toxicity in vivo. To model this effect in vitro, a cholinergic septal cell line (SN56) was exposed to Aβ. SN56 cells exhibited a tetraethylammonium (TEA)‐sensitive outward K+ current with delayed rectifier characteristics. Increases of 64% (±19; p < 0.02) and 44% (±12; p < 0.02) in K+ current density were noted 6–12 and 12–18 h following the addition of Aβ to SN56 cell cultures, respectively. Morphological observation and staining for cell viability showed that 25 ± 4 and 39 ± 4% of SN56 cells were dead after 48‐ and 96‐h exposures to Aβ, respectively. Perfusion of SN56 cells with 10–20 mM TEA blocked 71 ± 6 to 92 ± 2% of the outward currents, widened action potentials, elevated [Ca2+]i, and inhibited 89 ± 14 and 68 ± 14% of the Aβ toxicity. High [K+]o, which depolarizes cell membranes and increases [Ca2+]i, also protected SN56 cells from Aβ toxicity. This effect appeared specific since glucose deprivation of SN56 cells did not alter K+ current density and TEA did not protect these cells from hypoglycemic cell death. Furthermore, Aβ was toxic to a dopaminergic cell line (MES23.5) that expressed a K+ current with delayed rectifier characteristics; K+ current density was not altered by Aβ and MES23.5 cells were not protected by TEA from Aβ toxicity. In contrast, a noncholinergic septal cell line (SN48) that shows minimal outward K+ currents was resistant to the toxicity of Aβ. These data suggest that a K+ channel with delayed rectifier characteristics may play an important role in Aβ‐mediated toxicity for septal cholinergic cells.
Exercise promotes a subcellular redistribution of calcium-stimulated protease activity in striated muscle.

The aims of this study were (i) to investigate whether the contractile activity associated with running increases calcium-stimulated, calpastatin-inhibited protease activity (calpain-like) in a time-dependent manner and (ii) to determine whether the changes, if any, are proportionately distributed between soluble (cytosolic) and particulate (bound) fractions of striated muscle in vivo. Calcium-dependent, calpastatin-inhibited caseinolysis (i.e., calpain-like activity) was measured in control and exercised rats (25 m/min, 0% grade) at 2, 5, 15, 30, and 60 min. Total calpain-like activity in skeletal muscle increased by 26% (13.2 +/- 1.3 vs. 17.9 +/- 2.2 U/g wet wt.) (p < 0.05) after running (60 min), accompanied by an increased activity in the particulate fraction. In cardiac muscle, exercise (60 min) increased total calpain-like activity by 33% (p < 0.05), which was attributable to increases in both the cytosolic and particulate fractions. Both tissues responded with an early (2-5 min) activation of total calpain-like activity (p < 0.05), supported by early increases for particulate fractions from skeletal muscle; whereas for cardiac muscle, a noticeable early drop (p < 0.05) occurred in the particulate fraction. Minimal changes were observed for total, cytosolic, and particulate fractions of noncontracting tissue (i.e., liver). The results of this study support the hypothesis that the total calpain-like activity increases associated with level running occur early on with exercise and that the increases are accompanied by changes in the redistribution of soluble to particulate fractions. The changes would set the stage for enhanced rates of protein degradation known to occur in striated muscle with exercise.
The integration of human relationships in capital development projects: A case study of BSF scheme

Purpose – Recent work on public private partnerships (PPP)/private finance initiatives (PFI) and on the construction industry has emphasised the importance of knowledge transfer, learning and innovation to improve the working processes and procedures of the industry. However, until recently all three have been researched separately. It is on this basis the research presents a theoretical proposition that “the integration of alliance principles through the formation of collaborative network; innovation, knowledge transfer and organisational learning can be enabled where there is coordination, cohesion, commitment, teamwork, clear vision, monitoring and governance structure for control, risks/reward sharing, efficient and effective communication strategy, learning and knowledge transfer strategy”. Design/methodology/approach – The theory of social capital, social networks and inter‐organisational network was applied based on a network perspective to explain and aid specific attributes of PPP and PFI as a col.
Impacts of the financial crisis on luxury apparel and mass apparel companies from 2008 to 2011

The world financial crisis that started in 2007 had a profound impact on the global apparel industry, but at the firm level, the impact of the financial crisis seemed to be unevenly distributed. Several luxury apparel companies, such as Louis Vuitton, achieved stable net sales whereas quite a few mass apparel companies, such as GAP, experienced significant drop of sales and profits. The study intends to systematically compare the financial performance of luxury apparel companies with mass apparel companies from 2008 to 2011 to see whether a general pattern of differentiated performance exists between these two types of companies as a result of their respective business models and the specific impact of the 2008 financial crisis. MANOVA test was conducted based on six indices developed under the Dupont Strategic Profit Model (including annual growth rate of net sales, annual growth rate of cost of goods sold, gross margin percentage, net profit margin, asset turnover, and return on assets). Eight luxury apparel and eight mass apparel companies were selected for the purpose of the study. The results showed that first, the overall financial performance between luxury apparel and mass apparel companies was statistically different from 2008 to 2011. Second, luxury apparel and mass apparel companies had different gross margin and asset turnover from 2008 to 2011. Third, there was no evidence showing that luxury apparel and mass apparel companies achieved different growth of net sales, growth of cost of goods sold and return on assets (ROA) from 2008 to 2011. Fourth, luxury apparel companies outperformed mass apparel companies starting in 2010 in terms of net profit margin, indicating more robust post-crisis recovery. The results of the study confirmed the differentiated performance of selected luxury apparel and mass apparel companies’ business models. The findings also suggested that luxury apparel companies achieved a more robust post-crisis recovery. Additionally, the results suggested that mass apparel companies should not enter the luxury apparel market because ROA of luxury apparel companies did not appear to be better than mass apparel companies.