Miracle-dz/UniFAR-FTUs huggingface dataset:
A Critical Role of the PINCH-Integrin-linked Kinase Interaction in the Regulation of Cell Shape Change and Migration*

The interaction of cells with extracellular matrix recruits multiple proteins to cell-matrix contact sites (e.g. focal and fibrillar adhesions), which connect the extracellular matrix to the actin cytoskeleton and regulate cell shape change, migration, and other cellular processes. We previously identified PINCH, an adaptor protein comprising primarily five LIM domains, as a binding protein for integrin-linked kinase (ILK). In this study, we show that PINCH co-localizes with ILK in both focal adhesions and fibrillar adhesions. Furthermore, we have investigated the molecular basis underlying the targeting of PINCH to the cell-matrix contact sites and the functional significance of the PINCH-ILK interaction. We have found that the N-terminal LIM1 domain, which mediates the ILK binding, is required for the targeting of PINCH to the cell-matrix contact sites. The C-terminal LIM domains, although not absolutely required, play an important regulatory role in the localization of PINCH to cell-matrix contact sites. Inhibition of the PINCH-ILK interaction, either by overexpression of a PINCH N-terminal fragment containing the ILK-binding LIM1 domain or by overexpression of an ILK N-terminal fragment containing the PINCH-binding ankyrin domain, retarded cell spreading, and reduced cell motility. These results suggest that PINCH, through its interaction with ILK, is crucially involved in the regulation of cell shape change and motility.
Podocytes in HIV-Associated Nephropathy

HIV-associated nephropathy (HIVAN) is the leading cause of end-stage renal failure in HIV-1 seropositive patients. The pathologic findings include collapsing focal segmental glomerulosclerosis with proliferation of epithelial cells in Bowman’s space. Anatomically, these cells correspond to podocytes and exhibit a unique phenotype with loss of many differentiation markers including synaptopodin and dysregulation of the cell cycle markers consistent with proliferation. Podocyte dysfunction appears to be a direct result of HIV-1 protein expression, specifically Nef and Vpr as well as specific host factors that have yet to be elucidated. The mechanism by which Nef induces podocyte proliferation and dedifferentiation has been traced to its ability to activate several signaling pathways including Src-Stat3 and ras-raf-MAPK1, 2. Activation of the cAMP/PKA pathway with all-trans-retinoic acid appears to modulate these changes and returns podocytes to a differentiated, nonproliferating phenotype.
The administrative staff college at henley-on-thames

An analysis of the administrative staff concept approach to management education in England as exemplified in the General Management Course of and Administrative Staff College at Henley-on-Thames, which the author attended as a “staff observer. ” The philosophy, objectives and learning methods that have made the College an outstanding example of successful overseas management training are explained and, to the extent possible, evaluated.
Real Options: Applications in Public Economics

This paper illustrates the use of real options principles to value prototypical resource and industryinvestment projects. It captures important competitive/strategic dimensions in a step-by-stepanalysis of investment decisions (options) under uncertainty. It compares and contrasts staticdiscounted cash flow analysis (DCF) with real options analysis using three case studies. The initialexample values a resource extraction process using static DCF and then compares the projectvaluation when future information is valued and acted upon. The second example considers a coaldevelopment and uses the binomial valuation approach to capture the option value associated withhaving the right but not the obligation to exit the development. It contrasts this valuation approachagainst static DCF and highlights that future royalty payments could be underestimated if based onthe standard DCF valuation. The third example analyses the impact of providing a subsidy forhybrid vehicle production to accelerate potential uncertain environmental benefits. Lastly, thesuitability of the standard financial and economic evaluation tools used by treasury agencies isconsidered when projects contain real options.
Political Participation and E-Petitioning: An Analysis of the Policy-Making Impact of the Scottish Parliament's E-Petition System

Worldwide, representative democracies have experienced declining levels of voter turnout, lower membership levels in political parties, and apathy towards their respective political systems. E-democracy, specifically e-petitioning, has been touted as a possible solution to this problem by scholars of electoral systems. In 1999, the Scottish Parliament reconvened for the first time in nearly three hundred years, and set out to innovate Scottish politics by launching the world's first online e-petition system. The Scottish Parliament's e-petition system serves as a litmus test to see whether it offers an effective medium for increasing public political participation, and whether it can be replicated in other democratic countries. This study collected data from the Scottish Parliament's e-petitioning website, which hosts the e-petitions and details of who signed them, each e-petition's path through Parliament, and other important information. The success of an e-petition is highly subjective due to the original petitioner's desired goals; therefore, a data analysis and two case studies are utilized to evaluate the system. Results suggest that the Scottish Parliament's e-petition system has engaged Scots in the political process, giving them a medium to participate in policy formulation and to produce tangible changes in policy through their e-petitions.
Organisational Change and the Tensions of Decentralisation: the Case of Royal Mail

Miguel Martinez Lucio and Mike Noon, who are Lecturers in Industrial Relations and Organisational Behaviour respectively at the Cardiff Business School, draw on a case study of Royal Mail to explore the reasons for decentralisation and the issues this poses for managers and employees. They argue that the restructuring of Royal Mail was the result of three different imperatives for change: market, technological and political – pressurising managers to decentralise the formal structures of management-trade union relations. Decentralisation of these structures, however, has been far from a straightforward process: it has led to considerable tensions in the management of industrial relations, created scope for the development of new workplace industrial relations institutions and agendas, and given rise to a constant process of management reform.
Application of the VFO method to set-point control for the N-trailer vehicle with off-axle hitching

In this article the cascaded set-point feedback controller has been proposed for kinematics of the articulated mobile vehicle equipped with arbitrary number of off-axle hitched trailers. The concept results from geometrical features of the vehicle model, and from application of the Vector-Field-Orientation method in the outer loop of the cascaded controller. Solution presented in this article is formulated in the original configuration space of the vehicle not involving any auxiliary state or input transformation. It guarantees convergence of the last vehicle segment to the prescribed neighbourhood of a desired posture along with approximate straightening of a vehicle kinematic chain during approaching the destination. Practical limits of the control input amplitudes have been taken into account during the control law derivation by the application of a simple on-line scaling procedure to the nominally computed control functions. Results of numerical simulations illustrate effectiveness of the method for a 3-trailer vehicle.
The Structure of Strategy

This article takes a view of strategy which disputes the common distinctions between formulation and implementation, and between programmed and adaptive strategies. It argues that corporate success derives from a competitive advantage which is based on distinctive capabilities, which is most often derived from the unique character of a firm's relationships with its suppliers, customers or employees, and which is precisely identified and applied to relevant markets. Strategy is that process.
Labour-Skills, R and D and Capital Requirements in the International Trade and Investment of the United Kingdom 1968-78

During recent years observers of the UK economic scene have frequently commented on its ‘low level of technology’ and its ‘poor technological performance’. Translated into more specific terms, such observations seem to refer to the level of innovative activity in the UK and/or to its supply of engineers and other skilled-labour, relative to that in other advanced industrialised countries. Admittedly inter-country comparisons of these variables are often difficult, as different countries may use different indicators (and definitions) of innovative activity, have different types of educational qualifications, etc. Nevertheless, recent research does make possible some general comparisons. Pavitt (1981) reports, on the basis of industry-wide data on Research and Development (R and D) and international patenting, that innovative activity in the UK has in recent years been lagging behind that of its international competitors and the observation of Albu (1980) that in the supply of well qualified engineers and technologists the UK compares unfavourably with Japan and West Germany is reinforced by Prais (1981) in a more detailed comparative study of the UK and West Germany. Pending further research, these studies provide tentative evidence of the UK's relatively ‘low level of technology’.
Higher Education Quality: Perception Differences among Internal and External Stakeholders.

Conceptually, education quality of higher education can be determined by evaluation of their stakeholders’s satisfaction level. The Purpose of this study is to describe how students as external stakeholder and lecturers as internal stakeholder, perceived their satisfaction of learning experience in the university. This study was conducted in quantitative research method to collect, analyze and interpret data. The findings indicated that students and lecturers had different perceptions on the quality of education. Lecturer perceived all dimensions of quality with a higher satisfaction level than students. This finding shows that there is a gap between perception of lecturers and students on higher education quality.
Sperm‐mediated gene transfer in mice

Sperm‐mediated DNA transfer to offspring has the potential to markedly simplify the generation of transgenic animals, but the efficiency in mice has been controversial. To determine the basis of the variability of the procedure in mice, we undertook a large, collaborative study of sperm‐mediated DNA transfer to mouse eggs in well‐established laboratory conditions for in vitro fertilization and offspring development following embryo transfer. Sperm were incubated with plasmid DNA during the capacitation period and then added to freshly ovulated mouse oocytes for fertilization; cleaved embryos were then transferred to the oviducts of pseudopregnant recipients for gestation. From a total of 75 experiments, 13 produced 130 transgenic offspring, amounting to 7.4% of total fetuses. In five experiments, more than 85% of offspring were transgenic, but the factors leading to this high success rate were not discovered. Clustering of such a low frequency event could account for the disparate reports of transgenic success with sperm‐mediated DNA transfer to mouse offspring. Discovering the factors important to success would not only allow this simplified approach to become an important tool in the generation of transgenic mice, but could also lead to important insights into natural protective mechanisms against sperm‐mediated transfer of foreign DNA. Mol. Reprod. Dev. 50:406–409, 1998. © 1998 Wiley‐Liss, Inc.
Postoperative numbness of the knee following total knee arthroplasty.

INTRODUCTION The infrapatellar branch of the saphenous nerve is often injured during total knee arthroplasty (TKA), leading to numbness in its distribution distal to the incision. This is illustrated in a patient who suffered full-thickness burns to the lateral aspect of the knee from a hot water bottle. However, the proportion of patients who are informed of this phenomenon (as well as the effect of informing the patient of numbness) has not previously been studied according to the authors' knowledge. The aim of this study was to establish the proportion of patients with whom postoperative numbness was discussed during the consent procedure and whether this discussion was documented. METHODS A total of 73 patients (103 TKAs) agreed to take part in this study between 16 May and 9 July 2011. Patients were asked about their recollection of numbness being mentioned prior to the procedure as well as whether they experienced postoperative numbness. Statistical analysis was performed using SPSS®. RESULTS Subjective numbness was noted in 27% of the patients in this study. The prevalence of numbness decreased with time. Patients whose consent process included a discussion of numbness were 3.3 times more likely to report numbness after TKA (p=0.003). CONCLUSIONS Patient education regarding postoperative numbness increases the patient's awareness of any insensate skin that may develop. Numbness after TKA does improve with time but does not resolve completely. It is therefore recommended by the authors that numbness is discussed preoperatively with the patient and that this discussion is documented.
The Potential Impact of Large-Scale Voucher Programs

This review assesses the potential impact of large-scale voucher programs, drawing on empirical literature in economics, education, and sociology. The discussion is guided by three research questions, grounded within an economic framework. First, are private schools more efficient than public schools? Second, does the increasingly competitive schooling market promoted by vouchers cause public schools to become more efficient? And third, do vouchers result in increased student sorting across public and private schools–perhaps increasing segregation by socioeconomic status–and what does sorting portend for student outcomes? For some questions, there is a paucity of credible evidence. For others, evidence from non-voucher systems is used inappropriately to forecast the impact of vouchers. The review concludes that empirical evidence is not sufficiently compelling to justify, either strong advocacy or opposition to large-scale voucher programs.
Efficiency of Different Recruitment Strategies for Web Panels

The use of CAWI (Computer-Assisted Web Interviews) has increased greatly over the last decade, partly driven by technological development and increased Internet penetration, and partly by falling response rates in the traditional modes of polling (Baker et al., 2010 ; Curtin, Presser, & Singer, 2005 ; Couper 2000 ; Hansen, 2007 ). While some studies have found potential disadvantages to CAWI, e.g., higher levels of ‘‘ don’t know ’’ answers and high levels of break off (Heerwegh & Loosveldt, 2008 ; Peytchev, 2009 ), research also shows many advantages of CAWI compared to traditional modes: They are cost-efficient, allow automatic correction of errors and omissions during the interviews (Alvarez & Beselaere, 2005 ), and they lessen problems with social desirability bias towards interviewers (Baker et al., 2010 ; Kreuter, Presser, & Tourangeau, 2008 ). Furthermore, using web panels to conduct recurring CAWI with the same group of respondents let us build true time-series data which mitigates the problem of endogeneity inherent in so many public opinion studies. Additionally, modest differences are found when comparing results from web panels with traditional modes of surveys (Sanders, Clark, Stewart, & Whiteley, 2007 ), and web panels even display higher levels of data reliability than telephone surveys in some studies (Braunsberger, Wybenga, & Gates, 2007 ). One of the key challenges for web panels is recruitment of members. While numerous studies have investigated strategies to increase response rates in web surveys, relatively little research has looked specifically at recruitment strategies for web panels (Rao, Kaminska, & McCutcheon, 2010 ). Through an experimental design,
Polyclonal breast cancer metastases arise from collective dissemination of keratin 14-expressing tumor cell clusters

Significance Conventional models of cancer progression propose that single cells leave the primary tumor, enter the circulation, and seed clonal metastases. However, metastases can contain multiple clones, raising the question: How do polyclonal metastases form? We demonstrate that cancer cells seed distant organs as cohesive clusters, composed of two molecularly distinct subpopulations, whose proportions vary systematically during metastasis. We establish that collective dissemination is a frequent mechanism for metastasis and identify a molecular program in the most invasive, keratin 14+ (K14+) cancer cells, regulating cell–cell adhesion, cell–matrix adhesion, and immune evasion. We demonstrate that this metastatic phenotype is dependent upon K14 expression. Understanding the molecular basis of collective dissemination may therefore enable novel prognostics and therapies to improve patient outcomes. Recent genomic studies challenge the conventional model that each metastasis must arise from a single tumor cell and instead reveal that metastases can be composed of multiple genetically distinct clones. These intriguing observations raise the question: How do polyclonal metastases emerge from the primary tumor? In this study, we used multicolor lineage tracing to demonstrate that polyclonal seeding by cell clusters is a frequent mechanism in a common mouse model of breast cancer, accounting for >90% of metastases. We directly observed multicolored tumor cell clusters across major stages of metastasis, including collective invasion, local dissemination, intravascular emboli, circulating tumor cell clusters, and micrometastases. Experimentally aggregating tumor cells into clusters induced a >15-fold increase in colony formation ex vivo and a >100-fold increase in metastasis formation in vivo. Intriguingly, locally disseminated clusters, circulating tumor cell clusters, and lung micrometastases frequently expressed the epithelial cytoskeletal protein, keratin 14 (K14). RNA-seq analysis revealed that K14+ cells were enriched for desmosome and hemidesmosome adhesion complex genes, and were depleted for MHC class II genes. Depletion of K14 expression abrogated distant metastases and disrupted expression of multiple metastasis effectors, including Tenascin C (Tnc), Jagged1 (Jag1), and Epiregulin (Ereg). Taken together, our findings reveal K14 as a key regulator of metastasis and establish the concept that K14+ epithelial tumor cell clusters disseminate collectively to colonize distant organs.
Bean Consumption Is Associated with Greater Nutrient Intake, Reduced Systolic Blood Pressure, Lower Body Weight, and a Smaller Waist Circumference in Adults: Results from the National Health and Nutrition Examination Survey 1999-2002

Background: Epidemiological studies have shown positive findings associated with legume consumption and measures of cardiovascular disease and obesity. However, few observational trials have examined beans as a separate food variable when determining associations with health parameters. Objective: To determine the association of consuming beans on nutrient intakes and physiological parameters using the National Health and Examination Survey (NHANES) 1999-2002. Methods: Using data from NHANES 1999-2002, a secondary analysis was completed with a reliable 24-hour dietary recall where three groups of bean consumers were identified (N = 1,475). We determined mean nutrient intakes and physiological values between bean consumers and non-consumers. Least square means, standard errors and ANOVA were calculated using appropriate sample weights following adjustment for age, gender, ethnicity and energy. Results: Relative to non-consumers, bean consumers had higher intakes of dietary fiber, potassium, magnesium, iron, and copper (p's < 0.05). Those consuming beans had a lower body weight (p = 0.008) and a smaller waist size (p = 0.043) relative to non-consumers. Additionally, consumers of beans had a 23% reduced risk of increased waist size (p = 0.018) and a 22% reduced risk of being obese (p = 0.026). Also, baked bean consumption was associated with a lower systolic blood pressure. Conclusions: Bean consumers had better overall nutrient intake levels, better body weights and waist circumferences, and lower systolic blood pressure in comparison to non-consumers. These data support the benefits of bean consumption on improving nutrient intake and health parameters.
Using research to influence family services and policies: issues and challenges

There is growing national and international interest in the ways that research might influence policy and practice (Mullen, 2005; Nutley et al, 2007; Alexanderson et al, 2009; Ouimet et al, 2009; Widmer, 2009; Nutley et al, 2011). The articles in this Open Space section discuss how research is used to inform policy and practice development and how this relationship can be enhanced. They build on a dialogue at the Centre for Research on Families and Relationships’ (CRFR) national conference in November 2011, which considered the impact of social research. CRFR has been at the forefront of developing approaches to knowledge exchange on families and relationships research for the last 10 years (Morton and Nutley, 2011). The conference aimed to highlight interesting and innovative work and create a dialogue around ongoing issues and challenges. This introductory article considers some of the key issues and challenges around using research and it draws on presentations that the authors made at the conference. It begins by outlining what research use means and it then offers some emerging lessons about how such use can be improved. This is followed by reflections on how these lessons relate to the experiences of two units dedicated to improving research use: CRFR (Scotland) and the Knowledge Mobilization (KMb) Unit at York University (Toronto, Canada). Then the contribution of the other articles in the Open Space section to our understanding of the complexities of research use is discussed, and finally the future challenges are considered. This article reflects the authors’ perspectives and experiences. Sarah Morton has worked as a knowledge exchange practitioner for 10 years, she is co-director (Knowledge Exchange) at CRFR and has recently been investigating how research impact can be assessed. David Phipps is the director of Research Services & Knowledge Exchange at York University (Toronto, Canada) where he manages all research grants and contracts and has established the pioneering KMb Unit. Sandra Nutley is director of the Research Unit for Research Utilisation (www.ruru.ac.uk) and she is known internationally for her work on research use and evidence-based policy and practice.