Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparing translational population‐PBPK modelling of brain microdialysis with bottom‐up prediction of brain‐to‐plasma distribution in rat and human

The prediction of brain extracellular fluid (ECF) concentrations in human is a potentially valuable asset during drug development as it can provide the pharmacokinetic input for pharmacokinetic–pharmacodynamic models. This study aimed to compare two translational modelling approaches that can be applied at the preclinical stage of development in order to simulate human brain ECF concentrations. A population‐PBPK model of the central nervous system was developed based on brain microdialysis data, and the model parameters were translated to their corresponding human values to simulate ECF and brain tissue concentration profiles. In parallel, the PBPK modelling software Simcyp was used to simulate human brain tissue concentrations, via the bottom‐up prediction of brain tissue distribution using two different sets of mechanistic tissue composition‐based equations. The population‐PBPK and bottom‐up approaches gave similar predictions of total brain concentrations in both rat and human, while only the population‐PBPK model was capable of accurately simulating the rat ECF concentrations. The choice of PBPK model must therefore depend on the purpose of the modelling exercise, the in vitro and in vivo data available and knowledge of the mechanisms governing the membrane permeability and distribution of the drug. Copyright © 2014 John Wiley & Sons, Ltd.
Controlling the surface functionalities of nanoporous alumina membranes

A new approach for controlling and to functionalise nanoporous anodic alumina oxide (AAO) membranes is described. Our approach is predicated on the remarkable stability of the silanised AAO surface during anodisation. Well ordered nanoporous AAO membranes with different external surface properties compared to the internal pore surface properties were prepared and characterised.
Gene Expression Meta-Analysis of Potential Metastatic Breast Cancer Markers

Background: Breast cancer metastasis is a highly prevalent cause of death for European females. DNA microarray analysis has established that primary tumors, which remain localized, differ in gene expression from those that metastasize. Cross-analysis of these studies allow to revile the differences that may be used as predictive in the disease prognosis and therapy. Objective: The aim of the project was to validate suggested prognostic and therapeutic markers using meta-analysis of data on gene expression in metastatic and primary breast cancer tumors. Method: Data on relative gene expression values from 12 studies on primary breast cancer and breast cancer metastasis were retrieved from Genevestigator (Nebion) database. The results of the data meta-analysis were compared with results of literature mining for suggested metastatic breast cancer markers and vectors and consistency of their reported differential expression. Results: Our analysis suggested that transcriptional expression of the COX2 gene is significantly downregulated in metastatic tissue compared to normal breast tissue, but is not downregulated in primary tumors compared with normal breast tissue and may be used as a differential marker in metastatic breast cancer diagnostics. RRM2 gene expression decreases in metastases when compared to primary breast cancer and could be suggested as a marker to trace breast cancer evolution. Our study also supports MMP1, VCAM1, FZD3, VEGFC, FOXM1 and MUC1 as breast cancer onset markers, as these genes demonstrate significant differential expression in breast neoplasms compared with normal breast tissue. Conclusion: COX2 and RRM2 are suggested to be prominent markers for breast cancer metastasis. The crosstalk between upstream regulators of genes differentially expressed in primary breast tumors and metastasis also suggests pathways involving p53, ER1, ERB-B2, TNF and WNT, as the most promising regulators that may be considered for new complex drug therapeutic interventions in breast cancer metastatic progression.
Article in Press G Model the Journal of Systems and Software Spi Success Factors within Product Usability Evaluation

Keywords: Software process improvement Usability product metrics Process metrics Organisation Management Software development Software engineering Human–computer interaction User experience a b s t r a c t This article presents an experience report where we compare 8 years of experience of product related usability testing and evaluation with principles for software process improvement (SPI). In theory the product and the process views are often seen to be complementary, but studies of industry have demonstrated the opposite. Therefore, more empirical studies are needed to understand and improve the present situation. We find areas of close agreement as well as areas where our work illuminates new characteristics. It has been identified that successful SPI is dependent upon being successfully combined with a business orientation. Usability and business orientation also have strong connections although this has not been extensively addressed in SPI publications. Reasons for this could be that usability focuses on product metrics whilst today's SPI mainly focuses on process metrics. Also because today's SPI is dominated by striving towards a standardized, controllable, and predictable software engineering process; whilst successful usability efforts in organisations are more about creating a creative organisational culture advocating a useful product throughout the development and product life cycle. We provide a study and discussion that supports future development when combining usability and product focus with SPI, in particular if these efforts are related to usability process improvement efforts.
Kinetic analysis of γ-glutamyltransferase reaction process for measuring activity via an integration strategy at low concentrations of γ-glutamyl p-nitroaniline

At 0.12 mmol/L γ-glutamyl p-nitroaniline (GGPNA), an improved integrated method was developed for kinetic analysis of γ-glutamyltransferase (GGT) reaction process and the integration with the classical initial rate method to measure serum GGT. For the improved integrated method, an integrated rate equation, which used the predictor variable of reaction time and considered inhibitions by both GGPNA and products, was nonlinearly fit to GGT reaction processes. For the integration strategy, classical initial rates were estimated when GGPNA consumption percentages were below 50%; otherwise, maximal reaction rates of GGT were estimated by the improved integrated method and converted into initial rates according to the differential rate equation at 0.11 mmol/L GGPNA. The integration strategy was validated using optimized GGT kinetic parameters and 10-s intervals to record reaction curves within 8.0 min. By the integration strategy, there was a linear response from 0.9 to 32.0 U/L GGT, coefficients of variation were below 3.5% for GGT from 8.0 to 32.0 U/L (n=5), and GGT activities in clinical sera responded linearly to their classical initial rates at 2.00 mmol/L GGPNA with an expected slope. Therefore, the integration strategy was successful in measuring GGT at 0.12 mmol/L GGPNA.
A Molecular Genetic Approach to the Identification of Genes Expressed Predominantly in the Neuroendocrine and Immune Systems

Our results demonstrate that expression of neuropeptide tyrosine, one of the most abundant and widespread peptides in the mammalian nervous system, occurs in non-neuronal cells, in keeping with the emerging view that neuropeptide synthesis is not restricted to cells of the nervous system. RNA blot analyses and radioimmunoassays detected both NPY mRNA and NPY peptide in rat and mouse spleen, bone marrow, and peripheral blood cells. Immunohistochemical staining of sections from rat bone marrow with an NPY-specific antiserum revealed NPY-like immunoreactivity in megakaryocytes. In situ hybridization confirmed that the NPY-like peptide detected in megakaryocytes was synthesized de novo from NPY mRNA present in these cells. Megakaryocytes, the platelet-forming cells, originate from pluripotent hematopoietic stem cells present in the bone marrow as well as in the spleen of rodents. During microvascular damage, platelets aggregate at the damaged site and release bioactive substances. NPY is known to be a potent vasoconstrictor. Therefore, we propose that megakaryocyte-derived NPY is stored in platelets and released during platelet aggregation, resulting in a long-lasting vasoconstriction. Greatly elevated levels of megakaryocyte-derived NPY, as compared to the level found in BALB/C mice, were found in several mouse strains (NZB, NZB x W, and BXSB) which develop an autoimmune disease resembling systemic lupus erythematosus. Whether the elevation of megakaryocyte-derived NPY plays a role in the autoimmune disease progression in these mice or whether it merely reflects a related hematopoietic abnormality remains to be determined. Subtractive hybridization was used to isolate two cDNA clones that are predominantly expressed in the brain and the immune system. These and similarly derived cDNA clones will be used as molecular probes to study the mechanisms governing tissue-specific expression in the nervous and immune systems. Discovering the function of the proteins encoded by such cDNA clones may reveal evolutionary mechanisms shared by the nervous and immune systems, as well as a molecular basis for the interaction between these systems.
Identifying the Mechanisms for Workplace Burden of Psychiatric Illness

Background:Although previous research indicates that mental disorders detract from labor market outcomes, little is known about which psychiatric symptoms are most important. Objective:The objective of this study was to identify the mechanisms, or most important symptoms, through which psychiatric disorders affect labor market outcomes. We focus on major depressive episode, panic attack, social phobia, and generalized anxiety disorder. Our approach builds on prior work in that we consider the effects of symptoms both among individuals meeting and among individuals not meeting the diagnostic criteria for mental disorders. Research Design:Data were obtained from the National Comorbidity Survey Replication and the National Latino and Asian American Study. We used a structural equation model with latent indices for mental disorders, where the indices are generated from the model using multiple indicators (symptoms) and multiple causes of the disorders. Measures:The outcomes were current employment/labor force participation, weeks worked in last year, and number of work absences in the last month among employed individuals. Results:We found that for major depressive episode, symptoms of insomnia/hypersomnia, indecisiveness, severe emotional distress, and fatigue are crucial for labor market outcomes. In the case of generalized anxiety disorder, the length of the episode, symptoms relating to difficulty controlling worry, and symptoms of worry/anxiety/nervousness causing significant emotional distress were most detrimental for work outcomes. Social phobia and panic attack were not associated with labor market outcomes. Conclusion:Our findings suggest that interventions targeting these particular symptoms may be most helpful in improving work functioning.
An middleware for motion capture devices applied to virtual rehab

This demonstration allows the visitors to use assorted technologies to motion capture devices for uses in virtual rehabilitation. We presented the MixCap Middleware, developed to blend different types of motion capture technologies and to accomplish in one data format for biomechanical analysis. The Middleware, together with the associated prototypes were developed for use by health professionals who have low cost tracking movement equipment.
A re‐evaluation of social, environmental and sustainability accounting

Purpose – In responding to prior critiques, the paper seeks to re‐examine social accounting as a problem focused, multi‐disciplinary field and explores some of the possible directions the emerging field might take.Design/methodology/approach – The approach taken is a discursive, polemical essay.Findings – The very nature of social accounting as a problem‐based field seems to encourage – even require – that scholars approach the subject with a diversity of disciplinary methodological framings. In this regard, it may be apposite to view the field as an emerging, new trans‐disciplinary field.Research limitations/implications – As an essay, the paper seeks to stimulate thought and debate but it is ultimately speculative and personal.Originality/value – The paper continues the reflections upon the nature of social accounting (in the widest sense of the term) and offers some of the ways in which the new journal Sustainability Accounting, Management and Policy Journal, may articulate its purpose. The paper would.
catena-Poly[[cadmium-bis(μ-triethylenetetramine-κ4 N,N′:N′′,N′′′)-cadmium-(μ-triethylenetetramine-κ4 N,N′:N′′,N′′′)] hexafluoridogermanate]

The title fluoridogermanate, {[Cd2(C6H18N4)3][GeF6]}n, was synthesized hydrothermally. The crystal structure comprises undulated cationic [Cd2(TETA)3]4+ chains (TETA is triethylenetetramine) propagating parallel to [101]. The central CdII atom is six-coordinated in a CdN6 set by three TETA ligands. The isolated [GeF6]2− units, serving as counter-anions, occupy the inter-chain spaces and simultaneously link adjacent chains into a three-dimensional network through extensive N—H⋯F hydrogen-bonding interactions. One of the ethylene bridges of one TETA ligand is disordered around a twofold rotation axis.
Cultural adaptation in Chinese‐Western supply chain partnerships: Dyadic learning in an international context

Purpose – Inter‐firm learning, or dyadic learning, has been studied extensively in recent years: however very little attention has been devoted to extending the concept to an international context and no formal definition exists. The purpose of this paper is to propose “cultural adaptation” as a special form of international dyadic learning and link it to supply relationship performance.Design/methodology/approach – Case studies were conducted in four Chinese‐Western buyer‐supplier relationships, providing cross‐case replication, employing qualitative and quantitative methods. Data were triangulated by questionnaires, semi‐structured interviews, and documentation.Findings – Qualitative and quantitative evidence shows that cultural adaptation can lead to mutual benefits (relationship rents) and inbound spillover rents for both parties in a supply relationship.Research limitations/implications – Using four cases and a small sample of key informants completing the questionnaire limits generalisability of fin.
Hybridization and regional sex ratios in Nemophila menziesii

I tested whether a region of high female frequencies in the gynodioecious plant, Nemophila menziesii, may be due to hybridization between regionally distributed populations with different corolla colours. I crossed plants in the greenhouse from populations with different corolla colours and found that hybrid crosses yielded higher frequencies of females than within‐colour crosses. In the field, I found that populations with high female frequencies had intermediate mean corolla colours and higher variance in corolla colour, two traits suggesting hybridization. Nemophila menziesii has nuclear–cytoplasmic sex inheritance, thus if populations with different corolla colours are fixed for different male‐sterile cytoplasms and matching nuclear restorer alleles, hybridization between populations with different corolla colour should yield high frequencies of females. Two populations that are all hermaphroditic in the field segregated females in hybrid crosses suggesting that field populations may contain sex ratio distorters but appear undistorted, a prediction of genomic conflict theory.
Control of continuous polyhydroxybutyrate synthesis using calorimetry and flow cytometry

The substrate‐carbon flow can be controlled in continuous bioreactor cultures by the medium composition, for example, by the C/N ratio. The carbon distribution is optimal when a maximum fraction flows into the desired product and the residual is just sufficient to compensate for the dilution of the microbial catalyst. Undershooting of the latter condition is reflected immediately by changes in the Gibbs energy dissipation and cellular states. Two calorimetric measurement principles were applied to optimize the continuous synthesis of polyhydroxybutyrate (PHB) by Variovorax paradoxus DSM4065 during growth with constantly increasing supply rates of fructose or toxic phenol. Firstly, the changed slope of the heat production rate in a complete heat balanced bioreactor (CHB) indicated optimum carbon channeling into PHB. The extent of the alteration depended directly on the toxic properties of the substrate. Secondly, a flow through calorimeter was connected with the bioreactor as a “measurement loop. ” The optimum substrate carbon distribution was indicated by a sudden change in the heat production rate independent of substrate toxicity. The sudden change was explained mathematically and exploited for the long‐term control of phenol conversion into PHB. LASER flow cytometry measurements distinguished between subpopulations with completely different PHB‐content. Populations grown on fructose preserved a constant ratio of two subpopulations with double and quadruple sets of DNA. Cells grown on phenol comprised a third subpopulation with a single DNA set. Rising phenol concentrations caused this subpopulation to increase. It may thus be considered as an indicator of chemostress. © 2005 Wiley Periodicals, inc.
An exploratory study of the effects of the Sarbanes‐Oxley Act, the SEC and United States stock exchange(s) rules on audit committee alignment

Purpose – To investigate the recommendations of the Blue Ribbon Committee (BRC) and the requirements of the Sarbanes‐Oxley Act (SOX) on audit committee alignment.Design/methodology/approach – Using a unique set of hand collected data on audit committees for a sample of 129 firms during 1999, 2000, and 2002. This study is separated into two phases: the first phase of the study investigates the impact of the recommendations of the BRC on improving the effectiveness of audit committee on audit committee alignment; the second phase of the study investigates the impact of the SOX on audit committee alignment.Findings – For the BRC period, the results indicate that firms with audit committee alignment have larger total assets, have higher leverage and firms with audit committee alignment are more likely listed in NASDAQ. For the SOX period, the evidence suggests that firms with audit committee alignment are more likely to be associated with larger audit committee, higher directors' compensation, higher audit co.
(R,S)-3-Carboxy-2-(isoquinolinium-2-yl)propanoate monohydrate

The title compound, C13H11NO4·H2O, is a monohydrate of a betaine exhibiting a positively charged N-substituted isoquinoline group and a deprotonated carboxyl group. In the crystal, molecules are connected via short O—H⋯O hydrogen bonds between protonated and deprotonated carboxyl groups into chains of either R or S enantiomers along [001]. These chains are additionally connected by hydrogen bonding between water molecules and the deprotonated carboxy groups of neighbouring molecules.
Teachers and policy knowledge: a methodological and empirical study

Morgan, Grahame 2000. Teachers and Policy Knowledge: A Methodological and Empirical Study. A thesis submitted in partial fulfilment o f the requirements for the award o f file degree, Doctor o f Education (Faculty o f Education), at the University o f W ollongong, NSW. The New South Wales Department of Education and Training (DET) is a large and complex education authority employing some 50,000 teachers in school education and is responsible for the education of approximately 750,000 students of school age. This investigation examined the role of teachers in educational policy-making and supported the contention that primary and secondary school teachers, as a large professional group within the New South Wales DET, did not have a significant role in educational policy decision-making. It was also established that little research effort had been directed towards the definition and analysis of the proper role of these teachers in the policy process. The enquiry emphasised methodological and theoretical issues in the development of the research tools necessary to undertake this investigation. These tools were then applied throughout the investigation stage of the research and in proposing appropriate solutions to the problems identified. The methodology developed and applied synthesised aspects of literature review methods (Cooper, 1988; Bruce, 1994; Helmericks et al, 1991) and interdisciplinary research methods (Klein, 1990; Bechtell, 1986) in order to construct a methodology suitable for application to the research questions. Other aspects of policy research and policy studies (Majchrzak, 1984; Ham and Hill, 1984; Fasano, 1993) also guide the development and application of the methodology. Focus group methodology was applied in order to test the theoretical findings against the expressed opinions of teachers. The results of this study support the contention that school teachers should establish a more prominent role in policy decision-making in public education in NSW. In addition, the research suggested a solution in the form of a policy curriculum developed to improve teacher knowledge of the policy process and enhance access by teachers to policy-making. The significance of this enquiry is in making a contribution to the field of policy studies through the development of methodology and in the analysis of the social problem posed by the lack of teacher involvement in policy decision-making in public school education in NSW.
Relationship between motorized travel and time spent online for nonwork purposes: An examination of location impact

ABSTRACT The effects of information and communications technologies (ICT) on mobility have been investigated for several decades; however, few studies have focused on the amount of time spent using ICT, its implications on travel behavior, and how such relationships may vary with the characteristics of residential location. This study focuses on the Internet use for nonwork purposes and two research questions are examined: Does the amount of time spent on the Internet affect motorized trip generation and motorized travel distance? How do these effects vary according to residential location such as urban, town, and rural areas where the levels of accessibility are different? We find there is a nonlinear relationship between the amount of time spent on the Internet for personal purposes and motorized mobility (i.e., auto and public transit trips), with both very low-end as well as very high-end Internet users having lower levels of motorized mobility, while moderate-intensity users having higher levels of motorized mobility. However, these effects vary according to residential location; for example, people living in urban areas have different levels of motorized mobility according to the amount of time spent online, while no significant impact is identified for people living in rural area.