Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Domains of ExsA, the Transcriptional Activator of the Pseudomonas aeruginosa Type III Secretion System

ABSTRACT The opportunistic pathogen Pseudomonas aeruginosa utilizes a type III secretion system (T3SS) to evade phagocytosis and damage eukaryotic cells. Transcription of the T3SS regulon is controlled by ExsA, a member of the AraC/XylS family of transcriptional regulators. These family members generally consist of an ∼100-amino acid carboxy-terminal domain (CTD) with two helix-turn-helix DNA binding motifs and an ∼200-amino acid amino-terminal domain (NTD) with known functions including oligomerization and ligand binding. In the present study, we show that the CTD of ExsA binds to ExsA-dependent promoters in vitro and activates transcription from ExsA-dependent promoters both in vitro and in vivo. Despite possessing these activities, the CTD lacks the cooperative binding properties observed for full-length ExsA at the P exsC promoter. In addition, the CTD is unaffected by the negative regulatory activity of ExsD, an inhibitor of ExsA activity. Binding studies confirm that ExsD interacts directly with the NTD of ExsA. Our data are consistent with a model in which a single ExsA molecule first binds to a high-affinity site on the P exsC promoter. Protein-protein interactions mediated by the NTD then recruit an additional ExsA molecule to a second site on the promoter to form a complex capable of stimulating wild-type levels of transcription. These findings provide important insight into the mechanisms of transcriptional activation by ExsA and inhibition of ExsA activity by ExsD.
A proof-of-concept, randomized controlled trial of DAR-0100A, a dopamine-1 receptor agonist, for cognitive enhancement in schizophrenia

Background: Evidence from preclinical and human studies indicates the presence of reduced dopamine-1 receptor (D1R) signaling in the cortex, where D1Rs predominate, in patients with schizophrenia (SCZ), which may contribute to their cognitive deficits. Furthermore, studies in nonhuman primates (NHP) have suggested that intermittent administration of low doses of D1R agonists produce long-lasting reversals in cognitive deficits. The purpose of this trial was to test whether a similar design, involving subacute intermittent administration of low doses of a full, selective agonist at D1Rs, DAR-0100A, would improve cognitive deficits in SCZ. Methods: We randomized 49 clinically stable individuals with SCZ to three weeks of intermittent treatment with 0.5 mg or 15 mg of DAR-0100A, or placebo (normal saline). Functional magnetic resonance imaging (fMRI) BOLD was used to evaluate the effects of drug administration on brain activity during a working memory (WM) task. Effects on cognition were also assessed using the MATRICS and the N-back task as primary endpoints. The CogState battery was used as a secondary endpoint. Results: There were no observed treatment effects on either the BOLD fMRI signal during WM tasks or the WM domains of the MATRICS. Moderate improvement was detected on the CogState battery and on the attention domain of the MATRICS. Conclusion: These results suggest that low doses of D1 agonists that do not result in measureable occupancy of the D1R do not reliably improve cognition in SCZ, unlike the observations in NHP. As this drug is limited by its pharmacokinetic profile, better D1R agonists that can achieve adequate levels of D1R occupancy are needed to test the efficacy of this mechanism for cognitive enhancement in SCZ.
Auditor Industry Specialization, Auditor Changes, and Accounting Restatements

SYNOPSIS: The increasing occurrence of accounting restatements has drawn considerable attention from regulators, audit firms, and corporate boards concerning audit and financial statement quality. Research suggests that auditor industry specialization is associated with improved error detection and greater financial statement quality. We examine the impact of auditor industry specialization on a sample of restatement and nonrestatement firms and find that auditor industry specialization is negatively associated with the likelihood of accounting restatement. In addition, focusing on the subset of restatement firms, we find that auditor industry specialization reduces the likelihood of issuing restatements affecting core operating accounts, suggesting that industry specialization adds value in auditing a particularly critical area of the firms’ continuing operations. Finally, we find changing from a nonspecialist to a specialist auditor increases the likelihood of restatement, and changing from a specialist.
The Role of T Cells in Multiple Sclerosis: Implications for Therapies Targeting the T Cell Receptor

Abstract. The cause of multiple sclerosis (MS) is unknown, but an immunopathological process with both endogenous and exogenous factors contributing to disease seems likely. Considerable recent attention, triggered predominantly by findings in the animal model, experimental allergic encephalomyelitis (EAE), which resembles MS, has focused on the role of T cells in MS. Findings in the animal model have raised the possibility that demyelination could be produced by CD4+ T cells specific for myelin proteins and expressing a limited set of T cell receptor (TCR) molecules. Thus, specific therapies targeting T cells or more specifically the TCR could represent an effective treatment of MS as has been demonstrated in EAE. However, current studies of patients with MS indicate that the immunological mechanisms in MS are considerably more complicated than in EAE. The evidence for a pivotal role for T cells in MS and the characteristics of these T cells particularly with respect to TCR usage and potential for therapies directed at the TCR will be examined in this review.
Gender differences in student attitudes towards sexual appeals in print advertising

Sexuality is a widely used appeal in advertising today. The aim of this research was to establish whether or not this form of advertising connects with South African students and whether gender differences existed. A triangulated research design with data collected in focus groups, was used. The findings generally indicated negative attitudes towards sexual appeals in advertising. The main difference in gender responses was that males responded more negatively to adverts that contained male models as opposed to female models, whereas, women responded in similar ways regardless of the gender of the model.
The Pricing of Forward Contracts for Foreign Exchange

This paper investigates the nature of observed deviations from the unbiased expectations hypothesis in the forward foreign exchange market. If these deviations are due to risk premia then the same premia should be observed in nominal bonds denominated in different currencies. This condition imposes testable restrictions on the parameters of a mutivariate regression model. The empirical results are consistent with a world in which time varying risk premia cause the observed deviations from unbiased expectations.
Bioluminescent imaging of Ca2+ activity reveals spatiotemporal dynamics in glial networks of dark‐adapted mouse retina

Glial Ca2+ excitability plays a key role in reciprocal neuron–glia communication. In the retina, neuron–glia signalling is expected to be maximal in the dark, but the glial Ca2+ signal characteristics under such conditions have not been evaluated. To address this question, we used bioluminescence imaging to monitor spontaneous Ca2+ changes under dark conditions selectively in Müller cells, the principal retinal glial cells. By combining this imaging approach with network analysis, we demonstrate that activity in Müller cells is organized in networks of coactive cells, involving 2–16 cells located distantly and/or in clusters. We also report that spontaneous activity of small networks (2–6 Müller cells) repeat over time, sometimes in the same sequential order, revealing specific temporal dynamics. In addition, we show that networks of coactive glial cells are inhibited by TTX, indicating that ganglion and/or amacrine neuronal cells probably regulate Müller cell network properties. These results represent the first demonstration that spontaneous activity in adult Müller cells is patterned into correlated networks that display repeated sequences of coactivations over time. Furthermore, our bioluminescence technique provides a novel tool to study the dynamic characteristics of glial Ca2+ events in the retina under dark conditions, which should greatly facilitate future investigations of retinal dark‐adaptive processes.
Glass Ceilings versus Sticky Floors: Evidence from Southeast Asia and an International Update

type="main"> Using counterfactual decompositions combined with quantile regression, we investigate the pattern of gender wage differentials in Asian and Latin American countries and combine the findings with existing evidence for European and other mostly developed countries. While in the group of Latin American countries glass ceilings are prevalent, no clear evidence of glass ceilings is found in the group of Asian countries where, generally, sticky floors or a mixed pattern is the norm. The findings are robust with as well as without occupation controls. In addition, analysis by sector points to glass ceilings in the public sector in most countries, while in the private sector the patterns vary. Combining the new evidence from the present study with existing evidence (in total we consider 60 countries), a comprehensive global picture of gender wage differentials is provided. Possible explanations for differences in patterns of gender wage differentials are discussed.
An appraisal of the performance of two (2) Development Financial Institutions (DFIs) in Malaysia

This paper aims to assess the financial performance of two (2) Development Financial Institutions (DFIs) in Malaysia namely; Bank Simpanan Nasional or National Savings Bank (BSN) and Bank Kerjasama Rakyat Malaysia or Cooperative Bank (BR) for a period of 5 years spanning from 2006 to 2010. The DFIs are specialized financial institutions established by the government to achieve the socio-economic development objectives of the country through developing and promoting the key strategic sectors of the economy. In this study, we employed most commonly used financial ratio tools on a sample of two (2) development financial institutions to evaluate their performances so as to indicate how well they are prepared to meet the socio-economic development objectives of the country. To the best of our knowledge, related study assessing the performance of DFIs in Malaysia is scant. Thus realizing from the scarcity of studies on this component of financial system particularly in the case of Malaysia, we consider the present effort to be worthy addition to the existing literature in this line. To achieve our objectives, we used data and other relevant information collected from the annual reports of individual Development Financial Institutions under consideration. In addition, we also utilized Annual Reports of Bank Negara Malaysia or Central Bank of Malaysia (BNM-AR). The results showed that the financial health of the two DFIs under this study is sound but comparatively Bank Rakyat (BR) is in better position than its peer Bank Simpanan Nasional (BSN). The sound financial health also indicates the potential ability to cater the financial needs of the strategic sector of the economy towards achieving the socio-economic development objectives of the country.
Essays in efficiency and productivity analysis of microfinance institutions

This dissertation consists of three essays, each exploring MFIs’ efficiency and productivity dynamics in presence of environment impacts. The first essay examines technical efficiency and its determinants of 36 microfinance institutions in Sri Lanka using a two-stage double bootstrap approach. Efficiency levels are explored in terms of MFIs’ dual objectives of financial sustainability and outreach. In the first stage, a bootstrap Data Envelopment Analysis (DEA) procedure is used to correct the bias and construct confidential intervals for the efficiency estimates. Then in the second stage, bias-corrected efficiency estimates are regressed on a set of environmental variables using a bootstrap regression approach. The results of the first stage analysis confirm the existence of financial and social inefficiency for the majority of MFIs in Sri Lanka. The second stage analysis suggests that such inefficiency is determined by a number of MFI characteristics such as its age, its organizational type (i.e. run as an Non-governmental Organization or not), its capitalization level, and its profitability. The second essay uses a non-parametric Malmquist method to investigate the changes in productivity of 20 Kenyan microfinance institutions over the period 2009-2012. Productivity change is decomposed into indices of technological change, pure efficiency change and scale efficiency change. A bootstrap procedure is employed to construct confidence intervals for the Malmquist indices. This procedure makes it possible to investigate whether such changes are significant in a statistical sense. Additionally, a second-stage bootstrap procedure is employed to ascertain the sources of productivity change measures. Results show that productivity growths are primarily attributable to technical improvements at an average of 7%. Moreover, second stage results suggest that matured MFIs tend to have a lower productivity compared to the younger counterparts. In the third essay, focus is shifted to investigate the relationship between efficiency and corporate governance in MFIs. Using a two-stage bootstrap procedure for a sample of 36 Sri Lankan MFIs, it explores the effect of several governance models (i.e. board size, proportion of women on the board, duality and presence/ absence of a female chief executive officer) on sustainability and outreach dimensions of efficiency estimates. Results suggest that financial efficiency improves with a small board and higher proportion of women on the board. Results also show that MFIs in which the same individual holds CEO and chairman of the board and MFIs in which a woman holds the position of CEO are less efficient in terms of reaching the lower strata of the rural poor.
Bryoplana xerophila n. g. n. sp., a New Limnoterrestrial Microturbellarian (Platyhelminthes, Typhloplanidae, Protoplanellinae) from Epilithic Mosses, with Notes on Its Ecology

Bryoplana xerophila, a new genus and species of limnoterrestrial protoplanelline platyhelminth, was found in moss and soil covering a concrete wall in northern Alabama, USA. Bryoplana xerophila is the first taxon of limnoterrestrial Protoplanellinae recorded from North America and is one of the few rhabdocoels known from dry habitats. It is unique within Protoplanellinae in lacking rhabdites, having a pharynx rosulatus in the frontal half of the body, and lacking sclerotized parts in the male system. Notes on encystment, reproduction and feeding behavior are given. An updated identification key to all known genera of Protoplanellinae is presented.
Immunomodulatory Effects of Yersinia pestis Lipopolysaccharides on Human Macrophages

ABSTRACT In the current study, we investigated the activity of lipopolysaccharide (LPS) purified from Yersinia pestis grown at either 27°C or 37°C (termed LPS-27 and LPS-37, respectively). LPS-27 containing hexa-acylated lipid A, similar to the LPS present in usual gram-negative bacteria, stimulated an inflammatory response in human U937 cells through Toll-like receptor 4 (TLR4). LPS-37, which did not contain hexa-acylated lipid A, exhibited strong antagonistic activity to the TLR4-mediated inflammatory response. The phagocytic activity in the cells was not affected by LPS-37. To estimate the activity of LPS in its bacterial binding form, formalin-killed bacteria (FKB) were prepared from Y. pestis cells grown at 27°C or 37°C (termed FKB-27 and FKB-37, respectively). FKB-27 strongly stimulated the inflammatory response. This activity was suppressed in the presence of an anti-TLR4 antibody but not an anti-TLR2 antibody. In addition, this activity was almost completely suppressed by LPS-37, indicating that the activity of FKB-27 is predominantly derived from the LPS-27 bacterial binding form. In contrast, FKB-37 showed no antagonistic activity. The results arising from the current study indicate that Y. pestis causes infection in humans without stimulating the TLR4-based defense system via bacterial binding of LPS-37, even when bacterial free LPS-37 is not released to suppress the defense system. This is in contrast to the findings for bacteria that possess agonistic LPS types, which are easily recognized by the defense system via the bacterial binding forms.
PRIVATE-LABEL NPD PROCESS IMPROVEMENT IN THE UK FAST MOVING CONSUMER GOODS INDUSTRY

This paper contributes to the limited but growing body of literature on the topic of new product development performance within the world-class UK fast moving consumer goods industry. It reports the findings of the second phase of an applied research project called that involved Asda and six of its leading private-label suppliers. Based upon questionnaire responses that characterise the performance of 283 new product lines developed over a twenty-month period, this paper details the baseline operational (technical) and commercial performance of the standard Asda product development process called Bullseye. This data includes its innovation profile, success profile, value adding profile and time-based performance (cycle time and lead time). The paper highlights a number of relationships within this data that contravene some of the key findings in the existing literature. It also provides insight into the resulting interventions necessary to both the Bullseye process itself and its supporting performance measurement system in order to achieve significant performance improvement.
The Change from Private to Public Governance of British Higher Education: Its Consequences for Higher Education Policy Making 1980-2006.

This article argues that in moving from being self governed to being state governed the policy drivers for higher education are no longer those of the system itself but are derived from a set of policies designed for the reform and modernisation of the public sector of the economy. The formation of higher education policy therefore needs to be reinterpreted as an adjunct of public policy, rather than as something intrinsic to higher education. The impact of 'new public management' approaches and of political interventions are explored in illustrating the consequences of the centralisation of the management of the public services and of higher education becoming an issue in national politics.
Sources of Momentum Profits in International Stock Markets

type="main" xml:id="acfi12009-abs-0001"> This paper examines the sources of momentum profits of countries exhibiting and not exhibiting momentum and compares the differences in the underlying factors determining momentum profits between these two groups of countries. We find remarkable differences in the decomposed components between these two groups of countries. Countries exhibiting momentum show that the cross-sectional dispersion in unconditional mean returns dominates the negative contribution from the component reflecting the intertemporal behaviour of asset returns. However, this is not the case in countries exhibiting no momentum. Furthermore, countries with greater relative contribution from the cross-sectional variance in unconditional mean returns tend to have greater momentum profits. Our results may support risk-based explanations for the momentum phenomenon rather than behavioural finance-based explanations.
The anti-oxidant and anti-apoptotic activities of selenium in the prevention of myringosclerosis in rats

The possible effect of selenium on the prevention or reduction in occurrence of myringosclerosis was investigated. Fifteen rats were myringotomized bilaterally and separated into two groups. Nine rats were treated with selenium in the study group. Six rats were administered physiological serum and formed the control group. The occurrence of myringosclerotic lesions and anti-apoptotic activity in the tympanic membranes of the two groups were compared otomicroscopically and histopathologically. The sclerosis was occasional in three, moderate in five and severe in three tympanic membranes in the control group. On the other hand sclerosis was observed in only two of 18 specimens in the study group and sclerosis was seen only occasionally in these two sections. Although Bcl-2 staining, which indicates apoptosis, was not statistically different between the groups, it was observed that apoptosis was slightly more apparent in the study group (eight of 18 tympanic membranes versus two of 12 tympanic membranes in the control group). In conclusion, the formation of myringosclerosis following myringotomy in rats can be reduced by intraperitoneal selenium administration.
Efficient Procedures for Valuing European and American Path-Dependent Options

ALAN WHITE is also a professor in the Faculty of Management at the University of Toronto. We show how binomial and trinomial tree methods can be extended to value many types o f options with pathdependent payofs. Ourfirst example is a Iookback put option, whose payof is a function o f the maximum stock price realized during the option’s I@. Because the total number ofalternatives at a node is nevergreater than the number o f time steps, it is feasible to roll back through the tree and price the option at each node for every maximum stock price that could be realized up to that time. Derivatives such as Asian options based on the arithmetic average stock price present a more dficult problem, because the number ofaverage stock prices that might be realized between time zero and a node can be very large. In that case, at each node we price the option for a predetermined representative set of values f o r the path-dependent function the average, in this case and interpolate to calculate option values as required. Our results show that using the procedure to value Asian options is more accurate than a numerical approximation technique proposed in the literature, and is considerably faster than Monte Carlo simulation. Moreover, it can be used for both American and European options. We also illustrate applying the procedure to value mortgagebacked securities.
Hierarchical Service Placement for Demanding Applications

The increasing scale of cloud environments requires more scalable orchestration systems for determining which physical resources are responsible for processing service requests. A centralised service placement lacks scalability while a fully decentralised approach only has a limited view of the system. For these reasons, this paper investigates a hierarchical approach for service placement in a distributed environment, which increases scalability while maintains high service placement quality. First, we design a polynomial optimisation algorithm to place services in cloud data centers based on our novel utility function. Then, we describe a hierarchical model with the need to only know a small subset of the data required by the global optimisation formulation. Simulations show that our approach is scalable and performs well, close to the centralised model.