Serine and Threonine Phosphorylation of the Paxillin LIM Domains Regulates Paxillin Focal Adhesion Localization and Cell Adhesion to Fibronectin

We have previously shown that the LIM domains of paxillin operate as the focal adhesion (FA)-targeting motif of this protein. In the current study, we have identified the capacity of paxillin LIM2 and LIM3 to serve as binding sites for, and substrates of serine/threonine kinases. The activities of the LIM2- and LIM3-associated kinases were stimulated after adhesion of CHO.K1 cells to fibronectin; consequently, a role for LIM domain phosphorylation in regulating the subcellular localization of paxillin after adhesion to fibronectin was investigated. An avian paxillin-CHO.K1 model system was used to explore the role of paxillin phosphorylation in paxillin localization to FAs. We found that mutations of paxillin that mimicked LIM domain phosphorylation accelerated fibronectin-induced localization of paxillin to focal contacts. Further, blocking phosphorylation of the LIM domains reduced cell adhesion to fibronectin, whereas constitutive LIM domain phosphorylation significantly increased the capacity of cells to adhere to fibronectin. The potentiation of FA targeting and cell adhesion to fibronectin was specific to LIM domain phosphorylation as mutation of the amino-terminal tyrosine and serine residues of paxillin that are phosphorylated in response to fibronectin adhesion had no effect on the rate of FA localization or cell adhesion. This represents the first demonstration of the regulation of protein localization through LIM domain phosphorylation and suggests a novel mechanism of regulating LIM domain function. Additionally, these results provide the first evidence that paxillin contributes to “inside-out” integrin-mediated signal transduction.

Customizing for clients: developing a library liaison program from need to plan*

Building on the experiences of librarian representatives to curriculum committees in the colleges of dentistry, medicine, and nursing, the Health Science Center Libraries (HSCL) Strategic Plan recommended the formation of a Library Liaison Work Group to create a formal Library Liaison Program to serve the six Health Science Center (HSC) colleges and several affiliated centers and institutes. The work group's charge was to define the purpose and scope of the program, identify models of best practice, and recommend activities for liaisons. The work group gathered background information, performed an environmental scan, and developed a philosophy statement, a program of liaison activities focusing on seven |primary areas, and a forum for liaison communication. Hallmarks of the plan included intensive subject specialization (beyond collection development), extensive communication with users, and personal information services. Specialization was expected to promote competence, communication, confidence, comfort, and customization. Development of the program required close coordination with other strategic plan implementation teams, including teams for collection development, education, and marketing. This paper discusses the HSCL's planning process and the resulting Library Liaison Program. Although focusing on an academic health center, the planning process and liaison model may be applied to any library serving diverse, subject-specific user populations.

Building a retrospective collection in pharmacy: a brief history of the literature with some considerations for U.S. health sciences library professionals

This paper argues that historical works in pharmacy are important tools for the clinician as well as the historian. With this as its operative premise, delineating the tripartite aspects of pharmacy as a business enterprise, a science, and a profession provides a conceptual framework for primary and secondary resource collecting. A brief history and guide to those materials most essential to a historical collection in pharmacy follows. Issues such as availability and cost are discussed and summarized in checklist form. In addition, a glossary of important terms is provided as well as a list of all the major U.S. dispensatories and their various editions. This paper is intended to serve as a resource for those interested in collecting historical materials in pharmacy and pharmaco-therapeutics as well as provide a history that gives context to these classics in the field. This should provide a rationale for selective retrospective collection development in pharmacy.

A medical book collection for physician assistants

Selecting resources for physician assistants is challenging and can be overwhelming. Although several core lists exist for nursing, allied health, and medical libraries, judging the scope and level of these resources in relation to the information needs of the physician assistant is difficult. Medical texts can be highly specialized and very expensive, in essence, “overkill” for the needs of the physician assistant. This bibliography is meant to serve as a guide to appropriate medical texts for physician assistants. Titles were selected from the Brandon/Hill list, Doody's Electronic Journal, and various other reference resources. Resources were evaluated based on the subject and scope, audience, authorship, cost, and currency. The collection includes 195 titles from 33 specialty areas. Standard texts in each area are also included.

An automated multiplex oligonucleotide synthesizer: development of high-throughput, low-cost DNA synthesis.

An automated oligonucleotide synthesizer has been developed that can simultaneously and rapidly synthesize up to 96 different oligonucleotides in a 96-well microtiter format using phosphoramidite synthesis chemistry. A modified 96-well plate is positioned under reagent valve banks, and appropriate reagents are delivered into individual wells containing the growing oligonucleotide chain, which is bound to a solid support. Each well has a filter bottom that enables the removal of spent reagents while retaining the solid support matrix. A seal design is employed to control synthesis environment and the entire instrument is automated via computer control. Synthesis cycle times for 96 couplings are < 11 min, allowing a plate of 96 20-mers to be synthesized in < 5 hr. Oligonucleotide synthesis quality is comparable to commercial machines, with average coupling efficiencies routinely > 98% across the entire 96-well plate. No significant well-to-well variations in synthesis quality have been observed in > 6000 oligonucleotides synthesized to date. The reduced reagent usage and increased capacity allow the overall synthesis cost to drop by at least a factor of 10. With the development of this instrument, it is now practical and cost-effective to synthesize thousands to tens of thousands of oligonucleotides.

Enhancing Conservation Options: An Argument for Statutory Recognition of Options to Purchase Conservation Easements (OPCEs)

The most dynamic component of the conservation movement in the United States for the past three decades has been land conservation transactions. In the United States, land conservation organizations have protected roughly 40 million acres of land through transactions. Most of these acres have been protected using conservation easements. Climate change threatens the vast conservation edifice created by land conservation transactions. The tools of land conservation transactions are, traditionally, stationary. Climate change means that the resources that land conservation transactions were intended to protect may no longer remain on the land protected. Options to purchase conservation easements (OPCEs) have long played a modest but important role in conservation law practice. In the world climate change is creating, with its substantial uncertainties and shifting windows of opportunity, OPCEs can serve more complicated and strategic purposes. The ability of OPCEs to serve important roles in protecting land in the context of uncertainty would be significantly increased if state legislatures amend current conservation easement statutes to (1) specifically recognize OPCEs, (2) immunize OPCEs from a range of potential common law challenges, (3) guarantee the durability and transferability of OPCEs, and (4) integrate OPCEs into the burgeoning body of conservation easement law. These statutory amendments would do for OPCEs what conservation easement statutes have done for conservation easements: transform them into an essential multi-purpose tool for conservation in a changing world.

Construction of a Sustainable City Park in Ruddle, WV: A Model for Sustainable Park Design in Humid Climates

Three sustainable projects were studied under a sustainable park model for humid climates to determine where their costs lie in terms of installation, maintenance or both. These projects included the use of solar lighting to replace every configuration of conventional lighting, inclusion of a water garden/bog filter and Riparian Buffer System for the purposes of filtering sediments and nutrients out of runoff to prevent contaminated runoff from reaching the river that was adjacent to the park model location and construction of a LEED-inspired building to serve as the concession stand/restrooms building. The aggregate cost savings of instituting all three projects over ten years was $74,120 and the entire project paid itself off in approximately four years.

Letter from James Winthrop to Edward Wigglesworth, 1780 October 4

In this brief letter College Librarian James Winthrop requests that Harvard College Tutor William Bentley be allowed to serve as a deputy librarian.

[ Order to the sheriff of Bucks County], 1731

An order to the sheriff of Bucks County, Pennsylvania, for twelve men to serve on a jury in the trial of John Borrowes, for an unspecified crime. Signed: Jeremiah Langhorne (justice of the peace); dated 14 June 1731. With seal. With this document (originally attached) is the list of jurors chosen to serve at the trial.

Informational Barriers to Energy Efficiency - Theory and European Policies. Bruges European Economic Research (BEER) Papers 15/2009

This BEER addresses informational barriers to energy efficiency. It is a widely acknowledged result that an energy efficiency gap exists implying that the level of energy efficiency is at an inefficiently low level. Several barriers to energy efficiency create this gap and the presence of asymmetric information is likely to be one such barrier. In this article a theoretical framework is presented addressing the issues of moral hazard and adverse selection related to energy efficiency. Based on the theoretical framework, European policies on energy efficiency are evaluated. The article is divided into two main parts. The first part presents the theory on information asymmetries and its consequences on energy efficiency focusing on the problems of moral hazard and adverse selection. Having established a theoretical framework to understand the agency barriers to energy efficiency, the second part evaluates the policies of the European Union on energy efficiency. The BEER finds that problems of moral hazard and adverse selection indeed can help explain the seemingly low levels of energy. In both presented models the cost to the principal from implementing high energy efficiency outcome is increased with the informational asymmetries. The theory reveals two implications to policies on energy efficiency. First, the development of measures to enable contractual parties to base remuneration on energy performance must be enhanced, and second, the information on technologies and the education of consumers and installers on energy efficiency must be increased. This could be complemented with certification of installers and energy efficiency advisors to enable consumers to select good agents. Finally, it is found that the preferred EU policy instrument on energy efficiency, so far, seems to be the use of minimum requirements. Less used in EU legislation is the use of measuring and verification as well as the use of certifications. Therefore, it is concluded that the EU should consider an increased use of these instruments, and in particular focus on a further development of standards on measurability and verification as well as an increased focus on education of consumers as well as installers and advisors on energy efficiency.

Facilitating Mobility and Fostering Diversity: Getting EU Migration Governance to Respect the Human Rights of Migrants. CEPS Paper in Liberty and Security in Europe No. 92/May 2016

Migration towards Europe has surged over the past few years, overwhelming government authorities at the national and EU levels, and fuelling a xenophobic, nationalist, populist discourse linking migrants to security threats. Despite positive advances in the courts and worthy national initiatives (such as Italy’s Operation Mare Nostrum), the EU’s governance of migration and borders has had disastrous effects on the human rights of migrants. These effects stem from the criminalisation of migrants, which pushes them towards more precarious migration routes, the widespread use of administrative detention and the processing of asylum claims under the Dublin system, and now the EU–Turkey agreement. Yet, this paper finds that with the right political leadership, the EU could adopt different policies in order to develop and implement a human rights-based approach to migration that would seek to reconcile security concerns with the human rights of migrants. Such an approach would enable member states to fully reap the rewards of a stable, cohesive, long-term migration plan that facilitates and governs mobility rather than restricts it at immense cost to the EU, the member states and individual migrants.

Modelling the population cost-effectiveness of current and evidence-based optimal treatment for anxiety disorders

Background. The present paper describes a component of a large Population cost-effectiveness study that aimed to identify the averted burden and economic efficiency of current and optimal treatment for the major mental disorders. This paper reports on the findings for the anxiety disorders (panic disorder/agoraphobia, social phobia, generalized anxiety disorder, post-traumatic stress disorder and obsessive-compulsive disorder). Method. Outcome was calculated as averted 'years lived with disability' (YLD), a population summary measure of disability burden. Costs were the direct health care costs in 1997-8 Australian dollars. The cost per YLD averted (efficiency) was calculated for those already in contact with the health system for a mental health problem (current care) and for a hypothetical optimal care package of evidence-based treatment for this same group. Data sources included the Australian National Survey of Mental Health and Well-being and published treatment effects and unit costs. Results. Current coverage was around 40% for most disorders with the exception of social phobia at 21%. Receipt of interventions consistent with evidence-based care ranged from 32% of those in contact with services for social phobia to 64% for post-traumatic stress disorder. The cost of this care was estimated at $400 million, resulting in a cost per YLD averted ranging from $7761 for generalized anxiety disorder to $34 389 for panic/agoraphobia. Under optimal care, costs remained similar but health gains were increased substantially, reducing the cost per YLD to < $20 000 for all disorders. Conclusions. Evidence-based care for anxiety disorders would produce greater population health gain at a similar cost to that of current care, resulting in a substantial increase in the cost-effectiveness of treatment.

Cost of tobacco-related diseases, including passive smoking, in Hong Kong

Background: Costs of tobacco-related disease can be useful evidence to support tobacco control. In Hong Kong we now have locally derived data on the risks of smoking, including passive smoking. Aim: To estimate the health-related costs of tobacco from both active and passive smoking. Methods: Using local data, we estimated active and passive smoking-attributable mortality, hospital admissions, outpatient, emergency and general practitioner visits for adults and children, use of nursing homes and domestic help, time lost from work due to illness and premature mortality in the productive years. Morbidity risk data were used where possible but otherwise estimates based on mortality risks were used. Utilisation was valued at unit costs or from survey data. Work time lost was valued at the median wage and an additional costing included a value of US$1.3 million for a life lost. Results: In the Hong Kong population of 6.5 million in 1998, the annual value of direct medical costs, long term care and productivity loss was US$532 million for active smoking and US$156 million for passive smoking; passive smoking accounted for 23% of the total costs. Adding the value of attributable lives lost brought the annual cost to US$9.4 billion. Conclusion: The health costs of tobacco use are high and represent a net loss to society. Passive smoking increases these costs by at least a quarter. This quantification of the costs of tobacco provides strong motivation for legislative action on smoke-free areas in the Asia Pacific Region and elsewhere.

Warranty cost analysis for second-hand products

For second-hand products sold with warranty, the expected warranty cost for an item to the manufacturer, depends on (i) the age and/or usage as well as the maintenance history for the item and (ii) the terms of the warranty policy. The paper develops probabilistic models to compute the expected warranty cost to the manufacturer when the items are sold with free replacement or pro rata warranties. (C) 2000 Elsevier Science Ltd. All rights reserved.

Getting along with others:an examination of the ethnomethodological roots of perference organization and its relationship to complimenting

The well-established sociolinguistic literature on complimenting claims that compliments are formulaic (Manes and Wolfson 1981). The purpose of this thesis is to demonstrate that the claim is invalid, to describe an alternative approach to the study of compliments, and to draw on an extensive collection of compliments in order to show that complimenting is a diverse, interactive process. A prerequisite for such work is a means of deciding whether a given utterance is a compliment, but this issue is neglected in the literature. The conversation analytic notion of preference appeared capable of providing this criterion, but research revealed that it was too ill-defined to serve such a purpose. The thesis was, therefore, obliged to clarify the notion of preference before applying it to a study of compliments. The necessary clarification was found in the enthnomethodological roots of conversation analysis, and the thesis provides a clear and consistent means of determining whether utterances are preferred to dispreferred. The criteria used in the determination of preference are applied, in the final chapter, to the study of compliments. The results of the study contrast markedly with those of the sociolinguistic researchers, and they provide significant grounds for rejecting the claim that compliments are formulaic.