Miracle-dz/UniFAR-FTUs huggingface dataset:
Intermediate Structural States Involved in MRP1-mediated Drug Transport

Human multidrug resistance protein 1 (MRP1) is a member of the ATP-binding cassette transporter family and transports chemotherapeutic drugs as well as diverse organic anions such as leukotriene LTC4. The transport of chemotherapeutic drugs requires the presence of reduced GSH. By using hydrogen/deuterium exchange kinetics and limited trypsin digestion, the structural changes associated with each step of the drug transport process are analyzed. Purified MRP1 is reconstituted into lipid vesicles with an inside-out orientation, exposing its cytoplasmic region to the external medium. The resulting proteoliposomes have been shown previously to exhibit both ATP-dependent drug transport and drug-stimulated ATPase activity. Our results show that during GSH-dependent drug transport, MRP1 does not undergo secondary structure changes but only modifications in its accessibility toward the external environment. Drug binding induces a restructuring of MRP1 membrane-embedded domains that does not affect the cytosolic domains, including the nucleotide binding domains, responsible for ATP hydrolysis. This demonstrates that drug binding to MRP1 is not sufficient to propagate an allosteric signal between the membrane and the cytosolic domains. On the other hand, GSH binding induces a conformational change that affects the structural organization of the cytosolic domains and enhances ATP binding and/or hydrolysis suggesting that GSH-mediated conformational changes are required for the coupling between drug transport and ATP hydrolysis. Following ATP binding, the protein adopts a conformation characterized by a decreased stability and/or an increased accessibility toward the aqueous medium. No additional change in the accessibility toward the solvent and/or the stability of this specific conformational state and no change of the transmembrane helices orientation are observed upon ATP hydrolysis. Binding of a non-transported drug affects the dynamic changes occurring during ATP binding and hydrolysis and restricts the movement of the drug and its release.
Domain adaptation for pedestrian detection

Object detection is an essential component of many computer vision systems. The increase in the amount of collected digital data and new applications of computer vision have generated a demand for object detectors for many different types of scenes digitally captured in diverse settings. The appearance of objects captured across these different scenarios can vary significantly, causing readily available state-of-the-art object detectors to perform poorly in many of the scenes. One solution is to annotate and collect labelled data for each new scene and train a scene-specific object detector that is specialised to perform well for that scene, but such a method is labour intensive and impractical. In this thesis, we propose three novel contributions to learn scene-specific pedestrian detectors for scenes with minimal human supervision effort. In the first and second contributions, we formulate the problem as unsupervised domain adaptation in which a readily available generic pedestrian detector is automatically adapted to specific scenes (without any labelled data from the scenes). In the third contribution, we formulate it as a weakly supervised learning algorithm requiring annotations of only pedestrian centres. The first contribution is a detector adaptation algorithm using joint dataset feature learning. We use state-of-the-art deep learning for the purpose of detector adaptation by exploiting the assumption that the data lies on a low dimensional manifold. The algorithm significantly outperforms a state-of-the-art approach that makes use of a similar manifold assumption. The second contribution presents an efficient detector adaptation algorithm that makes effective use of cues (e.g spatio-temporal constraints) available in video. We show that, for videos, such cues can dramatically help with the detector adaptation. We extensively compare our approach with state-of-the-art algorithms and show that our algorithm outperforms the competing approaches despite being simpler to implement and apply. In the third contribution, we approach the task of reducing manual annotation effort by formulating the problem as a weakly supervised learning algorithm that requires annotation of only approximate centres of pedestrians (instead of the usual precise bounding boxes). Instead of assuming the availability of a generic detector and adapting it to new scenes as in the first two contributions, we collect manual annotation for new scenes but make the annotation task easier and faster. Our algorithm reduces the amount of manual annotation effort by approximately four times while maintaining a similar detection performance as the standard training methods. We evaluate each of the proposed algorithms on two challenging publicly available video datasets.
Voltage‐sensing phosphatase: actions and potentials

Voltage sensors have been well studied in voltage‐gated ion channels for neuronal excitation and muscle contraction. The recent discovery of a voltage‐sensing phosphatase, VSP, has changed the idea that voltage sensors are unique to ion flux through membranes. Recent findings on mechanisms and potential applications of VSP are reviewed.
Professional service relationships in chronic illness: the client's perspective

x CHAPTER ONEIntroduction . 1 1.0 Research Enquiry . 1 1.1 Background to the Research . 2 1.2 Client – Service Provider Relationships . 2 1.3 Professional Service Relationships. 5 1.4 Healthcare as a Professional Service . 5 1.5 Aim of the Study . 7 1.5. 1 Research Contribution . 7 1.5. 2 Methodology . 8 1.5. 3 Limitations and Key Assumptions . 9 1.6 Thesis Outline . 9 CHAPTER TWO Literature Review . 10 2.0 Introduction . 10 2.1 Background . 12 2.1.1 Customer value . 12 2.2 From Co-production to Co-creation . 13 2.2.1 Client Participation . 13 2.2.2 Co-creation of value. 14
Malnutrition in Hospitalized Children: A Responsibility and Opportunity for Pediatric Hospitalists.

Poor nutrition is an underrecognized cause of significant morbidity in hospitalized children.1,2 In addition to presenting with poor nutrition at the time of admission, children often suffer worsening of their nutritional status during the course of a hospitalization,3,4 often due to providers’ underrecognition of ongoing poor intake (see Fig 1). Pediatric hospitalists can and should play a central role in recognizing and treating this common comorbid condition. FIGURE 1 Percentage of BMI decrease ≥0.25 SD during hospitalization in 496 pediatric patients. Subjects were grouped by their Z -score at admission in the hospital. Although highly malnourished children lost the most in terms of BMI, even normally nourished children lost a statistically significant amount of weight during admission. Reprinted from Campanozzi A, Russo M, Catucci A, et al. Hospital-acquired malnutrition in children with mild clinical conditions. Nutrition 2009;25(5):540–547, with permission from Elsevier.3 [medium] In this article we highlight the important issue of malnutrition in hospitalized pediatric patients and propose a general approach to nutritional assessment and supplementation for the pediatric hospitalist. Malnutrition is defined as a state in which a deficiency (or excess) of energy, protein, and other nutrition causes measurable adverse effects on the body and on growth (in children), and may impact clinical outcome.5 The term “nutritional deterioration” has been used to describe significant weight loss in hospitalized children, a precursor to acute malnutrition. Although the term malnutrition includes both overnutrition (obesity) and undernutrition, in this article we focus specifically on undernutrition. Recent studies in developed countries have estimated the prevalence of malnutrition in hospitalized children as 12% to 24%. 1,3,5,6 Despite many medical advances over the past 20 years, the prevalence of malnutrition among hospitalized children has not decreased. Malnutrition is known to have detrimental effects …
Spiral elements for broad-band phased arrays

In this paper, we present a numerical analysis of an infinite periodic array of planar spiral elements with octave bandwidth. For off-broadside scan the array is found to exhibit very narrow resonances, which are independent of scan angle. They occur when the spiral arms are multiples of half a wavelength, in which case the current forms a high amplitude standing wave along the spiral arms. The resonances are conveniently suppressed by making the arms unequally long. We also discuss the equivalent 3-port for this nonsymmetrical array element and evaluate the element polarization performance.
The Pivotal Role of the Right Parietal Lobe in Temporal Attention

The visual system is extremely efficient at detecting events across time even at very fast presentation rates; however, discriminating the identity of those events is much slower and requires attention over time, a mechanism with a much coarser resolution [Cavanagh, P., Battelli, L. , & Holcombe, A. O. Dynamic attention. In A. C. Nobre & S. Kastner (Eds.), The Oxford handbook of attention (pp. 652–675). Oxford: Oxford University Press, 2013]. Patients affected by right parietal lesion, including the TPJ, are severely impaired in discriminating events across time in both visual fields [Battelli, L. , Cavanagh, P., & Thornton, I. M. Perception of biological motion in parietal patients. Neuropsychologia, 41, 1808–1816, 2003]. One way to test this ability is to use a simultaneity judgment task, whereby participants are asked to indicate whether two events occurred simultaneously or not. We psychophysically varied the frequency rate of four flickering disks, and on most of the trials, one disk (either in the left or right visual field) was flickering out-of-phase relative to the others. We asked participants to report whether two left-or-right-presented disks were simultaneous or not. We tested a total of 23 right and left parietal lesion patients in Experiment 1, and only right parietal patients showed impairment in both visual fields while their low-level visual functions were normal. Importantly, to causally link the right TPJ to the relative timing processing, we ran a TMS experiment on healthy participants. Participants underwent three stimulation sessions and performed the same simultaneity judgment task before and after 20 min of low-frequency inhibitory TMS over right TPJ, left TPJ, or early visual area as a control. rTMS over the right TPJ caused a bilateral impairment in the simultaneity judgment task, whereas rTMS over left TPJ or over early visual area did not affect performance. Altogether, our results directly link the right TPJ to the processing of relative time.
Social Networks, Learning, and Flexibility: Sourcing Scientific Knowledge in New Biotechnology Firms

This paper examines the organizational arrangements used by New Biotechnology Firms (NBFs) to source scientific knowledge. Using data from two highly successful NBFs, the paper shows that both firms relied principally on hierarchies and networks to source scientific knowledge; market arrangements were insignificant. Most interesting, each firm had a very large, diversified set of boundary-spanning collaborative research arrangements, mostly involving university scientists. It is argued that these external research networks enabled the two firms studied to compete more successfully in a highly turbulent and highly competitive industry environment.
Customers’ emotional reactions in the banking industry

Purpose – The purpose of this paper is to identify antecedents and consequences of customers’ emotional reactions in the banking industry. In this context, a model based on segmenting all variables into three segments is proposed. Design/methodology/approach – The research was conducted on a sample of 211 respondents. Data analysis was conducted in AMOS 18. In order to assess the overall model fit, confirmative factor analysis (CFA) was used. To test the research hypotheses, a structural equation model was used. Findings – The research results indicate that trust, social bonds, image and service quality are statistically significant drivers of satisfaction. Of these variables, only service quality has no significant impact on affective commitment. Trust stands out as the variable with the greatest impact on customer emotional responses. Satisfaction is also an important determinant of customers’ behavioral intentions. Practical implications – Results of the present study indicate that management should pa.
Experimental characterization and system simulations of depth of interaction PET detectors using 0.5 mm and 0.7 mm LSO arrays

Small animal PET scanners may be improved by increasing the sensitivity, improving the spatial resolution and improving the uniformity of the spatial resolution across the field of view. This may be achieved by using PET detectors based on crystal elements that are thin in the axial and transaxial directions and long in the radial direction, and by employing depth of interaction (DOI) encoding to minimize the parallax error. With DOI detectors, the diameter of the ring of the PET scanner may also be decreased. This minimizes the number of detectors required to achieve the same solid angle coverage as a scanner with a larger ring diameter and minimizes errors due to non-collinearity of the annihilation photons. In this study, we characterize prototype PET detectors that are finely pixelated with individual LSO crystal element sizes of 0.5 mm × 0.5 mm × 20 mm and 0.7 mm × 0.7 mm × 20 mm, read out at both ends by position sensitive avalanche photodiodes (PSAPDs). Both a specular reflector and a diffuse reflector were evaluated. The detectors were characterized based on the ability to clearly resolve the individual crystal elements, the DOI resolution and the energy resolution. Our results indicate that a scanner based on any of the four detector designs would offer improved spatial resolution and more uniform spatial resolution compared to present day small animal PET scanners. The greatest improvements to spatial resolution will be achieved when the detectors employing the 0.5 mm × 0.5 mm × 20 mm crystals are used. Monte Carlo simulations were performed to demonstrate that 2 mm DOI resolution is adequate to ensure uniform spatial resolution for a small animal PET scanner geometry using these detectors. The sensitivity of such a scanner was also simulated using Monte Carlo simulations and was shown to be greater than 10% for a four ring scanner with an inner diameter of 6 cm, employing 20 detectors per scanner ring.
Earnings Management and Audit Quality: Evidence from Southeast Asia

This thesis contributes quantitative and qualitative evidence from Southeast Asia to the literature on earnings management and audit quality. The association between earnings management and audit quality is investigated primarily by a new measure of audit quality and a new probit model. The new probit model tests the degree to which audit firms can be tolerant of earnings management at different levels of the artificial audit materiality. The tests of the probit model cover time-series data from 1992 to 2011 for 2,148 listed companies in Indonesia, Malaysia, the Philippines, Singapore and Thailand with a total of 20,757 firm-year observations. To extend the results of the probit model and to explore the stakeholders of audits’ perspectives on earnings management and audit quality, 16 semi-structured interviews with respondents from the audit firms, the listed companies, the regulators and the academic institute in Malaysia, Thailand and Singapore are also conducted. This thesis finds that the term earnings management is seen differently from its extant definition. In addition, this thesis provides evidence that the different roles in the process of an audit lead to different definitions and measures of audit quality; therefore, audit quality remains an imprecise measure. The evidence of this thesis also indicates that in the context of Southeast Asia, big firms have higher quality audits than non-big firms. This is likely to be because big firms are more concerned with their reputation and the serious consequences of an audit failure and big firms are perceived to have more resources. This thesis also explores whether long audit tenure impacts audit quality. The evidence on this suggests that audit partner rotation rather than audit firm rotation is being appointed by key stakeholders. Moreover, there is evidence that in comparison to audit firms from Singapore, those from Malaysia are more tolerant of earnings management whilst those from Indonesia, the Philippines and Thailand are less so. This thesis goes on to explore the possible impact of some national level factors such as the number of registrant audit firms, the use of non-English standards, corporate governance and type of legal system. From the probit model tests, it was found that non-English accounting standards and a limited number of registrant audit firms did not restrict audit quality, as perceived by some key stakeholders of audits.
Determination of perfluoroalkylated substances (PFASs) in drinking water from the Netherlands and Greece

In the present study 11 perfluoroalkylated substances (PFASs) were analysed in drinking tap water samples from the Netherlands (n = 37) and from Greece (n = 43) by applying LC-MS/MS and isotope dilution. PFASs concentrations above the limit of quantification, LOQ (0.6 ng/l) were detected in 20.9% of the samples from Greece. Total PFAS concentrations ranged between <LOQ and 5.9 ng/l, with the highest concentrations noted for the three Aegean islands Mykonos, Kalymnos and Syros and for the town Tripoli in the Peloponnese. In the Dutch situation, total PFASs concentrations above the LOQ were detected in 48.6% of the samples, varying from <LOQ to 54 ng/l. The highest concentrations were detected around Amsterdam (including Schiphol airport) and more generally, PFASs were detected in the drinking water from the western part of the Netherlands. This seems attributable to the source, which is purified surface water in this area. Short-chain PFASs and especially perfluoropentanoic acid (PFPeA), perfluorohexanoic acid (PFHxA), perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorobutane sulfonate (PFBS), and perfluorohexane sulfonate (PFHxS) were detected most frequently, whereas long-chain PFASs (C > 8) were only rarely detected. In the drinking water samples from the eastern part of the Netherlands, where drinking water is sourced from groundwater reservoirs, no PFASs were detected. This demonstrates that exposure to PFASs through drinking water in the Netherlands is dependent on the source. Additionally, five samples of bottled water from each country were analysed in the current study, with all of them originating from ground wells. In these samples, all PFASs were below the LOQ.
Priced Liquidity Risk Factors at the Oslo Stock Exchange

We examine how liquidity risk influences stock returns at the Oslo Stock Exchange by investigating if differences between returns are related to liquidity, and how liquidity should be measured. A wide range of distinct liquidity measures is studied, and the measures which best express liquidity risk are combined to a multifactor model. We use a multi-perspective approach to select and compare measures, and perform Fama-MacBeth regressions to evaluate the performance of factor combinations. We find liquidity risk to be priced. Turnover is found to be the liquidity measure that best captures liquidity risk, and trade-based measures are found to be more important than order-based measures. Our multifactor model consisting of amortized spread, trading volume, turnover in shares and the market factor seem to perform better than the capital asset pricing model (CAPM) empirically, and can be used as an alternative to the CAPM for practical applications. Both common and non-common variances of measures are important to express liquidity risk, and we suggest that asset pricing models should include several liquidity measures.
Apical-to-basolateral transcytosis of photoreceptor outer segments induced by lipid peroxidation products in human retinal pigment epithelial cells.

PURPOSE Progressive accumulation of extracellular material at the basolateral side of the retinal pigment epithelium (RPE) is a key event in the pathogenesis of age-related macular degeneration (AMD). The authors previously demonstrated that modifications with lipid peroxidation products, such as 4-hydroxynonenal (HNE) and malondialdehyde (MDA), stabilize photoreceptor outer segment (POS) proteins against lysosomal degradation. Herein, they tested RPE cells for the basolateral release of undegraded modified POS proteins. METHODS Polarized cultures of the human RPE cell line ARPE-19 on permeable membranes were incubated with iodine-125-labeled POS on the apical side. After 24 hours, radioactivity was quantified in apical medium, cell lysates, and basolateral medium after separation of undegraded proteins by precipitation. Protein composition of basolaterally released POS material was analyzed by two-dimensional gel electrophoresis. C3a- and SC5b-9-specific enzyme-linked immunosorbent assays were used to assess complement activation by modified POS. RESULTS The amount of phagocytic uptake was similar for native and modified POS. Unmodified POS proteins were almost completely (98.1%) degraded, whereas degradation of HNE- and MDA-modified POS proteins was significantly reduced (47.2%; 56.5%). Undegraded POS proteins accumulated intracellularly (14.2%; 12.1%) and were trafficked through the cells to be released into the basolateral medium (38.5%; 31.5%). Protein composition of basolaterally released material matched the original POS preparations. Protein modifications did not confer increased complement-activating capacity to POS material. CONCLUSIONS Inhibition of lysosomal degradation by lipid peroxidation-related protein modifications induces apical-to-basolateral transcytosis of undegraded POS proteins by human RPE cells in vitro. This mechanism may contribute to sub-RPE deposit formation and drusen biogenesis in AMD.
PENGARUH PROFESIONALISME TERHADAP KOMITMEN ORGANISASI DALAM UPAYA MENINGKATKAN KINERJA AUDITOR (STUDI PADA KANTOR PERWAKILAN BPK-RI PROVINSI ACEH )

This research is done at BPK branch office Aceh Province which aim is to know how big the influence of professionalism and organization commitment toward auditor performance at BPK branch office Aceh Province, and to know if there is or no influence of professionalism to organization commitment at BPK branch office Aceh Province either simultaneously or partially. This research use sample method. Respondens of this research are the auditors at BPK branch office Aceh Province. The objective of this research is to be able to seek the correlation of professionalism to organization commitment and auditor performance with 44 auditors samples of populations 78 auditors who is taken at stratifide random sampling. Technics of data analysis the used is path analysis. The analysis indicate that beta scor for the influence of X₁ to X₂ is 0,379, X₁ to Y is 0,485 and X₂ to Y is 0,032. Result of this research indicate that auditor professionalism and organization commitment have significan influence toward auditors performance at BPK branch office Aceh Province by simultaneously. Partially, auditor professionalism have influence to organization commitment and auditors performance at BPK branch office Aceh Province, but do not have influence the organization commitment to auditors performance at BPK branch office Aceh Province by parsially. Keyword : professionalism, organization commitment, and auditors performance.