Expansion, harvest and cryopreservation of human mesenchymal stem cells in a serum-free microcarrier process

Human mesenchymal stem cell (hMSC) therapies are currently progressing through clinical development, driving the need for consistent, and cost effective manufacturing processes to meet the lot-sizes required for commercial production. The use of animal-derived serum is common in hMSC culture but has many drawbacks such as limited supply, lot-to-lot variability, increased regulatory burden, possibility of pathogen transmission, and reduced scope for process optimization. These constraints may impact the development of a consistent large-scale process and therefore must be addressed. The aim of this work was therefore to run a pilot study in the systematic development of serum-free hMSC manufacturing process. Human bone-marrow derived hMSCs were expanded on fibronectin-coated, non-porous plastic microcarriers in 100mL stirred spinner flasks at a density of 3×10⁵cells.mL^-1 in serum-free medium. The hMSCs were successfully harvested by our recently-developed technique using animal-free enzymatic cell detachment accompanied by agitation followed by filtration to separate the hMSCs from microcarriers, with a post-harvest viability of 99.63±0.03%. The hMSCs were found to be in accordance with the ISCT characterization criteria and maintained hMSC outgrowth and colony-forming potential. The hMSCs were held in suspension post-harvest to simulate a typical pooling time for a scaled expansion process and cryopreserved in a serum-free vehicle solution using a controlled-rate freezing process. Post-thaw viability was 75.8±1.4% with a similar 3h attachment efficiency also observed, indicating successful hMSC recovery, and attachment. This approach therefore demonstrates that once an hMSC line and appropriate medium have been selected for production, multiple unit operations can be integrated to generate an animal component-free hMSC production process from expansion through to cryopreservation.

A high-efficiency solar rankine engine with isothermal expansion

Though the principle of the solar Rankine cycle is well known, with several examples reported in the literature, there is yet a scarcity of engines that could be efficiently applied in small-scale (<100 KW) applications. Hence, this paper presents a variant of the engine that uses an isothermal expansion to achieve a theoretical efficiency close to the Carnot limit. Generation of steam inside the power cylinder obviates the need for an external boiler. The device is suitable for slow-moving applications and is of particular interest for driving a batch-desalination process. Preliminary experiments have shown cycle efficiency of 16%, and a high work ratio of 0.997. ©The Author 2013. Published by Oxford University Press. All rights reserved.

An Expansion Formula for Fractional Derivatives and its Application

An expansion formula for fractional derivatives given as in form of a series involving function and moments of its k-th derivative is derived. The convergence of the series is proved and an estimate of the reminder is given. The form of the fractional derivative given here is especially suitable in deriving restrictions, in a form of internal variable theory, following from the second law of thermodynamics, when applied to linear viscoelasticity of fractional derivative type.

Asymptotic Expansion of Solution for Almost Regular and Weakly Perturbed Systems of Ordinary Differential Equations

Л. И. Каранджулов, Н. Д. Сиракова - В работата се прилага методът на Поанкаре за решаване на почти регулярни нелинейни гранични задачи при общи гранични условия. Предполага се, че диференциалната система съдържа сингулярна функция по отношение на малкия параметър. При определени условия се доказва асимптотичност на решението на поставената задача.

Does Atkinson-Wilcox Expansion Converges for any Convex Domain?

2000 Mathematics Subject Classification: 35C10, 35C20, 35P25, 47A40, 58D30, 81U40.

The external dimension of EU justice and home affairs after the Lisbon Treaty::analysing the dynamics of expansion and diversification

The article introduces a research framework for analysing the external dimension of EU Justice and Home Affairs after the Lisbon Treaty. The dynamics of expansion and diversification, discernable for both the EU policy-making and the scholarly work dedicated to it, are at the centre of the article and constitute a common reference point for the present Special Issue. These dynamics have been triggered through deliberate decisions of involved policy-makers as well as through unintended spillover effects from other policy areas and/or decisions. The article also engages with the theoretically informed literature on the subject, which struggles with the definition of what this dimension actually constitutes, as well as how to best capture the practices of this field.We take stock of the scholarly debates by comparing the diverse approaches and discussing how much they complement each other and/or present different dimensions of a single ‘policy universe’.

Foglalkoztatás-bővítési kilátások és akadályok az üzleti szférában(Employment expansion prospects and obstacles in the business sphere)

Empirikus vizsgálatok szerint a vállalatok fejlesztési törekvéseit Magyarországon is elsősorban a piaci kilátások határozzák meg, a finanszírozási körülmények szerepe jóval gyengébb. A beruházások és innovációk végrehajtása elsősorban a műszaki végzettségűek iránti keresletet növelheti, a szakképzetlen dolgozók körében viszont gyakran leépítésekre vezet. A vállalatok igénye és az állást keresők kompetenciái azonban nemcsak a szakmastruktúrában térnek el. A korábban megvalósított fejlesztéseknek a válság idején munkahelymegtartó szerepe volt. A jövőbeni fejlesztések munkaerőigényének kielégítésében mind az üzleti szektor szereplőinek, mind a szakpolitikáknak fontos tennivalói vannak. _______ According to recent empirical research development efforts of companies in Hungary are primarily determined by the market outlook, the role of financing conditions is much weaker. Implementation of investments and innovation can increase in first row the demand for technical professionals and often causes dismissals in unskilled labour. The demand of companies and competences of job seekers diverge not only in the professional structure. Earlier fulfilled development had workplace keeping role during the recession. Both actors of business sector and policies have important tasks to do in satisfying labour demand of future developments.

Canals as Vectors for Fish Movement: Potential Southward Range Expansion of Lepisosteus osseus L. (Longnose Gar) in South Florida

Lepisosteus osseus (Longnose Gar) is a large-bodied predator, whose Florida distribution remains unclear at the southern edge of its range. We reviewed available literature and museum voucher specimens to provide a more accurate range description, and we discuss recent collections in south Florida. Longnose Gar has not been previously reported in natural habitats south of Lake Okeechobee. Instead, records south of the lake are from canals, and most are recent (since 2000), including our own southernmost 2011 record. No records from Everglades natural habitats have been collected. Previous studies have shown native range expansions in anthropogenically disturbed landscapes. We suggest that the Longnose Gar is expanding its range southward in Florida using canals as dispersal vectors and/or suitable habitat.

Essays of strategic alliance portfolio configuration—Its performance properties, strategic antecedents and consequential effects on multinational firms' continuing foreign expansion

This dissertation focused on an increasingly prevalent phenomenon in today's global business environment—strategic alliance portfolio. Building on resource-based view, resource dependency theory and real options theory, this dissertation adopted a multi-dimensional perspective to examine the performance implications, strategic antecedents of alliance portfolio configuration, and its strategic effects on firms' decision-making on their continuing foreign expansion. The dissertation consisted of three interrelated essays, each of which dealt with a specific research question. In the first essay I applied a two-dimensional construct that embraces both alliance relations' and alliance partners' attributes to illustrate alliance portfolio configuration. Based on this framework, a longitudinal study was conducted attempting to explore the performance properties of alliance portfolio configuration. The results revealed that alliance diversity and partner diversity have different relative contributions to firms' economic performance. The relationship between alliance portfolio configuration and firm performance was shaped by degree of multinationality in a curvilinear pattern. The second essay attempted to identify the firm level driving forces of alliance portfolio configuration and how these forces interacting with firms' internationalization influence firms' strategic choices on alliance portfolio configuration. The empirical results indicated that past alliance experience, slack resource and firms' brand images are three critical determinants shaping alliance portfolios, but those shaping relationships are conditioned by firms' multinationality. The third essay primarily employed real options theory to build a conceptual framework, revealing how country-, alliance portfolio-, firm-, and industry level factors and their interactions influence firms' strategic decision-making on post-entry continuing expansion in foreign markets. The two empirical studies were resided in global hospitality and travel industries and use panel data to test the relevant theoretical models. Overall, the dissertation advanced and enriched the theoretical domain of alliance portfolio. It particularly shed valuable insights on three fundamental questions in the domain of alliance portfolio research, namely "if and how alliance portfolios contribute to firms' economic performance"; "what determines the appearance of alliance portfolios”; and "how alliance portfolios affect firms' strategic decision-making". This dissertation also extended the international business and strategic management research on service multinationals' foreign expansion and performance.

Nonnative African jewelfish are more fit but not bolder at the invasion front: a trait comparison across an Everglades range expansion

This material is based upon work supported by the National Science Foundation through the Florida Coastal Everglades Long-Term Ecological Research program under Cooperative Agreements #DBI-0620409 and #DEB-9910514. Any opinions, findings, conclusions, or recommendations expressed in the material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.

Pirates, exiles, and empire: English seamen, Atlantic expansion, and Jamaican settlement, 1558–1658

A life of piracy offered marginal men a profession with a degree of autonomy, despite the brand of "outlaw" and the fear of prosecution. At various times throughout history, governments and crowned heads suspended much of their piracy prosecution, licensing men to work as "privateers" for the state, supplementing naval forces. This practice has a long history, but in sixteenth-century England, Elizabeth I (1558-1603) significantly altered this tradition. Recognizing her own weakness in effectively prosecuting these men and the profit they could contribute to the government, Elizabeth began incorporating pirates into the English naval corps in peacetime—not just in war. This practice increased English naval resources, income, and presence in the emerging Atlantic World, but also increased conflict with the powerful Spanish empire. By 1605, making peace with Spain, James VI/I (1603-1625) retracted Elizabeth's privateering promotion, prompting an emigration of English seamen to the American outposts they had developed in the previous century. Now exiles, no longer beholden to the Crown, seamen reverted back to piracy. The Carolinas and Jamaica served as bases for these rover communities. In 1650, the revolutionary leader Oliver Cromwell (1649-1658) once again recognized the merits of such policies. Determined to demonstrate his authority and solidify his rule, Cromwell offered citizenship and state support to Caribbean exiles in exchange for their aiding of his navy in the taking of Spanish Jamaica. Official chartering of Port Royal, Jamaica served as reward for these men's efforts and as the culmination of a century-long cycle of piracy legislation, creating one of England's most lucrative colonies in the middle of a traditionally Spanish Caribbean empire. Through legal and diplomatic records, correspondence, and naval and demographic records from England and Spain, this dissertation explores early modern piracy/privateering policy and its impact on the development of the Atlantic World. European disputes and imperial competition converged in these piracy debates with significant consequences for the definitions of criminality and citizenship and for the development of Atlantic empire.

What does board capital really bring to the table? Exploring the effect of directors' human and social capital on effective governance during international expansion

What constitutes effective corporate governance? Which director characteristics render boards effective at positively influencing firm-level performance outcomes? This dissertation examines these questions by taking a multilevel, multidisciplinary approach to corporate governance. I explore the individual-, team-, and firm- level factors that enable directors to serve effectively as strategic resources during international expansion. I argue that directors' international experience improves their ability to serve as effective strategic consultants and resource providers to firms during the complex internationalization process. However, unlike prior research, which tends to assume that directors with the potential to provide important resources uniformly do so, I acknowledge contextual factors (i.e. board cohesiveness, strategic relevance of directors' experience) that affect their propensity to actually influence outcomes. I explore these issues in three essays: one review essay and two empirical essays.^ In the first empirical essay, I integrate resource dependence theory with insights from social-psychological research to explore the influence of board capital on firms' cross-border M&A performance. Using a sample of cross-border M&As completed by S&P 500 firms from 2004-2009, I find evidence that directors' depth of international experience is associated with superior pre-deal outcomes. This suggests that boards' deep, market-specific knowledge is valuable during the target selection phase. I further find that directors' breadth of international experience is associated with superior post-deal performance, suggesting that these directors' global mindset helps firms in the post-M&A integration phase. I also find that these relationships are positively moderated by board cohesiveness, measured by boards' internal social ties.^ In the second empirical essay, I explore the boundary conditions of international board capital by examining how the characteristics of firms' internationalization strategy moderate the relationship between board capital and firm performance. Using a panel of 377 S&P 500 firms observed from 2004-2011, I find that boards' depth of international experience and social capital are more important during early stages of internationalization, when firms tend to lack market knowledge and legitimacy in the host markets. On the other hand, I find that breadth of international experience has a stronger relationship with performance when firms' have higher scope of internationalization, when information-processing demands are higher.^

Latitudinal shift in thermal niche breadth results from thermal release during a climate-mediated range expansion

Funded by Biodiversity and Ecosystem Services in a Changing Climate Wenner-Gren Foundation Swedish Research Council The Royal Swedish Academy of Sciences Stiftelsen Anna-Greta Holger Crafoords Fund The Crafoord Foundation

Latitudinal shift in thermal niche breadth results from thermal release during a climate-mediated range expansion

Funded by Biodiversity and Ecosystem Services in a Changing Climate Wenner-Gren Foundation Swedish Research Council The Royal Swedish Academy of Sciences Stiftelsen Anna-Greta Holger Crafoords Fund The Crafoord Foundation