Antisense-induced myostatin exon skipping leads to muscle hypertrophy in mice following Octa‑guanidine morpholino oligomer treatment

Myostatin is a negative regulator of muscle mass, and several strategies are being developed to knockdown its expression to improve muscle-wasting conditions. Strategies using antimyostatin-blocking antibodies, inhibitory-binding partners, signal transduction blockers, and RNA interference system (RNAi)-based knockdown have yielded promising results and increased muscle mass in experimental animals. These approaches have, however, a number of disadvantages such as transient effects or adverse immune complications. We report here the use of antisense oligonucleotides (AOs) to manipulate myostatin pre-mRNA splicing and knockdown myostatin expression. Both 2’O-methyl phosphorothioate RNA (2’OMePS) and phosphorodiamidate morpholino oligomers (PMO) led to efficient exon skipping in vitro and in vivo and knockdown of myostatin at the transcript level. The substantial myostatin exon skipping observed after systemic injection of Vivo-PMO into normal mice led to a significant increase in soleus muscle mass as compared to the controls injected with normal saline suggesting that this approach could be feasible to ameliorate muscle-wasting pathologies.

Synoptic preconditions for extreme flooding during the summer Asian Monsoon in the Mumbai area

The summer monsoon season is an important hydrometeorological feature of the Indian subcontinent and it has significant socioeconomic impacts. This study is aimed at understanding the processes associated with the occurrence of catastrophic flood events. The study has two novel features that add to the existing body of knowledge about the South Asian Monsoon: 1) combine traditional hydrometeorological observations (rain gauge measurements) with unconventional data (media and state historical records of reported flooding) to produce value-added century-long time-series of potential flood events, and 2) identify the larger regional synoptic conditions leading to days with flood potential in the time-series. The promise of mining unconventional data to extend hydrometeorological records is demonstrated in this study. The synoptic evolution of flooding events in the western-central coast of India and the densely populated Mumbai area are shown to correspond to active monsoon periods with embedded low-pressure centers and have far upstream influence from the western edge of the Indian Ocean basin. The coastal processes along the Arabian Peninsula where the currents interact with the continental shelf are found to be key features of extremes during the South Asian Monsoon

The Mid-Brunhes Event and West Antarctic ice sheet stability

The complex cyclical nature of Pleistocene climate, driven by the evolving orbital configuration of the Earth, is well known but not well understood. A major climatic transition took place at the Mid-Brunhes Event (MBE), ca. 430 ka ago after which the amplitude of the ca.100 ka climate oscillations increased, with substantially warmer interglacials, including periods warmer than present. Recent modelling has indicated that while the timing of these warmer-than-present transient (WPT) events is consistent with southern warming due to a deglaciation-forced slowdown of the Atlantic Meridional Overturning Circulation, the magnitude of warming requires a local amplification, for which a candidate is the feedback of significant West Antarctic Ice Sheet (WAIS) retreat. We here extend this argument, based on the absence of WPTs in the early ice core record (450–800 ka ago), to hypothesize that the MBE could be a manifestation of decreased WAIS stability, triggered by ongoing subglacial erosion.

Creation of the WATCH Forcing Data and Its Use to Assess Global and Regional Reference Crop Evaporation over Land during the Twentieth Century

The Water and Global Change (WATCH) project evaluation of the terrestrial water cycle involves using land surface models and general hydrological models to assess hydrologically important variables including evaporation, soil moisture, and runoff. Such models require meteorological forcing data, and this paper describes the creation of the WATCH Forcing Data for 1958–2001 based on the 40-yr ECMWF Re-Analysis (ERA-40) and for 1901–57 based on reordered reanalysis data. It also discusses and analyses modelindependent estimates of reference crop evaporation. Global average annual cumulative reference crop evaporation was selected as a widely adopted measure of potential evapotranspiration. It exhibits no significant trend from 1979 to 2001 although there are significant long-term increases in global average vapor pressure deficit and concurrent significant decreases in global average net radiation and wind speed. The near-constant global average of annual reference crop evaporation in the late twentieth century masks significant decreases in some regions (e.g., the Murray–Darling basin) with significant increases in others.

A comparative performance analysis of TRMM 3B42 (TMPA) versions 6 and 7 for hydrological applications over Andean-Amazon river basins

The Tropical Rainfall Measuring Mission 3B42 precipitation estimates are widely used in tropical regions for hydrometeorological research. Recently, version 7 of the product was released. Major revisions to the algorithm involve the radar refl ectivity - rainfall rates relationship, surface clutter detection over high terrain, a new reference database for the passive microwave algorithm, and a higher quality gauge analysis product for monthly bias correction. To assess the impacts of the improved algorithm, we compare the version 7 and the older version 6 product with data from 263 rain gauges in and around the northern Peruvian Andes. The region covers humid tropical rainforest, tropical mountains, and arid to humid coastal plains. We and that the version 7 product has a significantly lower bias and an improved representation of the rainfall distribution. We further evaluated the performance of versions 6 and 7 products as forcing data for hydrological modelling, by comparing the simulated and observed daily streamfl ow in 9 nested Amazon river basins. We find that the improvement in the precipitation estimation algorithm translates to an increase in the model Nash-Sutcliffe effciency, and a reduction in the percent bias between the observed and simulated flows by 30 to 95%.

The catastrophic flash-flood event of 8–9 September 2002 in the Gard region, France: a first case study for the Cévennes–Vivarais Mediterranean Hydrometeorological Observatory

The Cévennes–Vivarais Mediterranean Hydrometeorological Observatory (OHM-CV) is a research initiative aimed at improving the understanding and modeling of the Mediterranean intense rain events that frequently result in devastating flash floods in southern France. A primary objective is to bring together the skills of meteorologists and hydrologists, modelers and instrumentalists, researchers and practitioners, to cope with these rather unpredictable events. In line with previously published flash-flood monographs, the present paper aims at documenting the 8–9 September 2002 catastrophic event, which resulted in 24 casualties and an economic damage evaluated at 1.2 billion euros (i.e., about 1 billion U.S. dollars) in the Gard region, France. A description of the synoptic meteorological situation is first given and shows that no particular precursor indicated the imminence of such an extreme event. Then, radar and rain gauge analyses are used to assess the magnitude of the rain event, which was particularly remarkable for its spatial extent with rain amounts greater than 200 mm in 24 h over 5500 km2. The maximum values of 600–700 mm observed locally are among the highest daily records in the region. The preliminary results of the postevent hydrological investigation show that the hydrologic response of the upstream watersheds of the Gard and Vidourle Rivers is consistent with the marked space–time structure of the rain event. It is noteworthy that peak specific discharges were very high over most of the affected areas (5–10 m3 s−1 km−2) and reached locally extraordinary values of more than 20 m3 s−1 km−2. A preliminary analysis indicates contrasting hydrological behaviors that seem to be related to geomorphological factors, notably the influence of karst in part of the region. An overview of the ongoing meteorological and hydrological research projects devoted to this case study within the OHM-CV is finally presented.

Can British multinational enterprises finance economic development in South East Asia?

Purpose – The purpose of this paper is to shed new light on the debate about the role of foreign direct investment (FDI) and public policy in fostering economic development. Specifically, can the capital inflow of multinational enterprises (MNEs) and the ability of the subsidiaries to raise funds locally help promote development? This paper addresses this issue by examining the capital structure and financing sources of foreign subsidiaries of MNEs. Design/methodology/approach – This paper integrates the capital structure theories in finance with internalization theory in international business. It uses an original primary dataset collected by a survey of 101 foreign subsidiaries of British MNEs in six emerging economies in the ASEAN region. Findings – There are three significant findings. First, these subsidiaries rely heavily on internal funds generated within the MNEs and less on external debts raised in the host countries. Second, the foreign subsidiary's capital structure is influenced by the home country of origin of the parent firm and the parent firm's financing sources. Third, these subsidiaries have used the financial resources to develop business networks with local small and medium enterprises (SMEs) which contribute to economic development of the host countries. Originality/value – This paper examines the internal capital market within the MNE. It provides theoretical and empirical support for the capital structure theory of the hierarchy financing approach and also for internalization theory by addressing FDI inflows by MNEs and the raising of funds locally. These findings have important implications for public policy, namely the facilitation of MNE entry to encourage economic development.

The research productivity of the AIB Farmer Award finalists

Purpose – This paper aims to analyze the research productivity and impact of the finalists of the AIB best dissertation award, now titled the Buckley and Casson Award, but from 1987 to 2012 the Farmer Award. Specifically, this paper examines whether there is a relationship between winning the best dissertation award and subsequent publication productivity and impact. Relationships between academic institution and institutional geographic location and finalists are also examined. Design/methodology/approach – The paper examines 25 years of citation counts and the number of publications in Google Scholar of Farmer Award winners and finalists of the AIB best dissertation award from inception in 1987 to 2009, with cited publications as a measure of productivity and citations as a measure of impact. Top performers in productivity and impact are identified, and the averages of winners and non-winners are analyzed in aggregate, over time and per year. Data on finalists' institution and geographic location of institution are analyzed to describe the importance of location and institution to the award. Findings – It is found that the overall average citations of the winners of the award is less than that of the non-winners, and that in the large majority of years the non-winners have an average citation count higher than that of the winners. However, taking averages in five year increments shows more mixed results, with non-winners performing better in two periods and winners performing better in two periods, with the remaining period being split as to research productivity and impact. Originality/value – Aggarwal et al. in this journal summarized a variety of data on Farmer Award finalists from the 1990s to gain insights on institutions represented by finalists, the publication record of finalists, and content of dissertations, among other characteristics. This paper updates some of the insights from that paper by examining data on award winners from 1987 to 2013, and adds further insight by examining for the first time cited publications and citation counts winners and non-winners for the same period excluding the last two years.

PEG−peptide conjugates

The remarkable diversity of the self-assembly behavior of PEG−peptides is reviewed, including self-assemblies formed by PEG−peptides with β-sheet and α-helical (coiled-coil) peptide sequences. The modes of self-assembly in solution and in the solid state are discussed. Additionally, applications in bionanotechnology and synthetic materials science are summarized.

The empirical literature on multinational enterprises, subsidiaries and performance

Purpose – This paper aims to provide a synthetic review of the empirical literature on the multinational enterprise (MNE), subsidiaries and performance. Design/methodology/approach – The paper examines the following: the theoretical and conceptual foundation of multinationality (M) and performance (P) measures; the impact of MNE strategic investment motives on performance; the influence of contextual external and internal environment factors on performance; the strategy to optimize value chain activities of the MNE by cooperating with external partners in an asymmetric network, the key drivers of enhanced shareholder value and the implications of performance; and the need to access primary data provided by firms and managers themselves when analyzing the internal functioning of the MNE and its subsidiaries. Findings – The overall message from this literature review is that empirical research should be designed on the basis of relevant theoretical and conceptual foundations of the performance construct. Originality/value – The paper provides a systematic and synthetic review of theoretical and empirical literature.

Self-assembly of a Model Peptide incorporating a Hexa-Histidine sequence attached to an Oligo-Alanine sequence, and binding to Gold NTA/Nickel nanoparticles

Amyloid fibrils are formed by a model surfactant-like peptide (Ala)10-(His)6 containing a hexahistidine tag. This peptide undergoes a remarkable two-step self-assembly process with two distinct critical aggregation concentrations (cac’s), probed by fluorescence techniques. A micromolar range cac is ascribed to the formation of prefibrillar structures, whereas a millimolar range cac is associated with the formation of well-defined but more compact fibrils. We examine the labeling of these model tagged amyloid fibrils using Ni-NTA functionalized gold nanoparticles (Nanogold). Successful labeling is demonstrated via electron microscopy imaging. The specificity of tagging does not disrupt the β-sheet structure of the peptide fibrils. Binding of fibrils and Nanogold is found to influence the circular dichroism associated with the gold nanoparticle plasmon absorption band. These results highlight a new approach to the fabrication of functionalized amyloid fibrils and the creation of peptide/nanoparticle hybrid materials.

Asset recombination in international partnerships as a source of improved innovation capabilities in China

Purpose This paper examines how multinational enterprises (MNEs) and local partners, including suppliers, customers, and competitors in China, improve their innovation capabilities through collaboration. We analyse this collaboration as a three-way interaction between the ownership-specific (O) advantages or firm-specific assets (FSAs) of the MNE subsidiary, the FSAs of the local partner, and the location-specific assets of the host location. Design/methodology/approach Our propositions are examined through a survey of 320 firms, supplemented with 30 in-depth case studies, based in mainland China. Findings We find that the recombination of asset-type (Oa) FSAs and transaction-type (Ot) FSAs from both partners leads to new innovation-related ownership advantages, or ‘recombinant advantages’. Ot FSAs, in the form of access to local suppliers, customers or government networks are particularly important for reducing the liability of foreignness for MNEs. Originality/value The study reveals important patterns of reciprocal transfer, sharing, and integration for different asset categories (tacit, codified) and different forms of FSA and explicitly links these to different innovation performance outcomes. The paper reports on these findings, making an empirical contribution in an important context (China-based partnerships). We also contribute to conceptual developments, connecting various kinds of FSA, tacit and codifiable assets and ‘recombinant advantages’. Limited conceptual, methodological, and empirical contributions are made in linking asset integration with (measurable) innovation performance outcomes in international partnerships.

Challenges of operational river forecasting

Skillful and timely streamflow forecasts are critically important to water managers and emergency protection services. To provide these forecasts, hydrologists must predict the behavior of complex coupled human–natural systems using incomplete and uncertain information and imperfect models. Moreover, operational predictions often integrate anecdotal information and unmodeled factors. Forecasting agencies face four key challenges: 1) making the most of available data, 2) making accurate predictions using models, 3) turning hydrometeorological forecasts into effective warnings, and 4) administering an operational service. Each challenge presents a variety of research opportunities, including the development of automated quality-control algorithms for the myriad of data used in operational streamflow forecasts, data assimilation, and ensemble forecasting techniques that allow for forecaster input, methods for using human-generated weather forecasts quantitatively, and quantification of human interference in the hydrologic cycle. Furthermore, much can be done to improve the communication of probabilistic forecasts and to design a forecasting paradigm that effectively combines increasingly sophisticated forecasting technology with subjective forecaster expertise. These areas are described in detail to share a real-world perspective and focus for ongoing research endeavors.

Regionalization strategy and performance: the moderating role of industry dynamism and top management team diversity

Purpose– This paper contributes to the debate about the performance implications of adopting a regional as opposed to a global strategic posture. The aim of this paper is to argue that the performance effects of a regionalization strategy vary based on the characteristics of the industry in which the MNE operates and the composition of its top management team (TMT). Design/methodology/approach– This analysis is based on a cross‐sectional dataset of 211 large European MNEs headquartered in four Western European economies at the end of 2005. Findings– Results show that firms adopting a regional orientation outperform MNEs with global strategic positioning. This positive relationship is less pronounced under conditions of industry dynamism and inter‐regional TMT diversity. Originality/value– The study contributes to our understanding of whether and under what conditions MNEs benefit from adopting a regional as opposed to a global strategic posture.

The economic theory of the firm as a foundation for international business theory

The economic theory of the firm is central to the theory of the multinational enterprise. Recent literature on multinationals, however, makes only limited reference to the economic theory of the firm. Multinationals play an important role in coordinating the international division of labour through internal markets. The paper reviews the economic principles that underlie this view. Optimal internalisation equates marginal benefits and costs. The benefits of internalisation stem mainly from the difficulties of licensing proprietary knowledge, reflecting the view that MNEs possess an ‘ownership’ or ‘firm-specific’ advantage. The costs of internalisation, it is argued, reflect managerial capability, and in particular the capability to manage a large firm. The paper argues that management capability is a complement to ownership advantage. Ownership advantage determines the potential of the firm, and management capability governs the fulfilment of this potential through overcoming barriers to growth. The analysis is applied to a variety of issues, including out-sourcing, geographical dispersion of production, and regional specialisation in marketing.