ABSTRACT
The C ii deficit, which describes the observed decrease in the ratio of C ii 158 μm emission to continuum infrared emission in galaxies with high star formation surface densities, places a ...significant challenge to the interpretation of C ii detections from across the observable universe. In an attempt to further decode the cause of the C ii deficit, the C ii and dust continuum emission from 18 Local Volume galaxies has been split based on conditions within the interstellar medium where it originated. This is completed using the Key Insights in Nearby Galaxies: a Far-Infrared Survey with Herschel (KINGFISH) and Beyond the Peak (BtP) surveys and the wide-range of wavelength information, from UV to far-infrared emission lines, available for a selection of star-forming regions within these samples. By comparing these subdivided C ii emissions to isolated infrared emission and other properties, we find that the thermalization (collisional de-excitation) of the C ii line in H ii regions plays a significant role in the deficit observed in our sample.
•The study firstly focuses on mapping the lagging-behind European regions.•Co-patenting is used to define networking capacity of local organisations.•Panel modelling is implemented based on RegPat ...and Eurostat databases.•Results suggest wider interregional networks perform better than local networks.•Collaborations with knowledge-intensive regions are specifically relevant.
In rapidly changing regional economies, less innovative European regions (henceforth referred to as lagging-behind regions) must actively work to reduce the gap between them and knowledge-intensive regions. Recent literature has stressed that the lack of efficient institutional settings reduces the opportunities of local knowledge spillover and increases the need for local organisations to exploit collaborative networks to better support their innovation performance. In this light, since increasing attention has recently been directed at the role of inter-regional collaborations, we have measured the capacity of local innovative organisations embedded in lagging-behind European regions to develop internal and external regional inventors’ networks by exploring their collaborative patenting processes. Then, a seven-year panel dataset (2002–2008) was organised using patents data at a regional level to validate the research hypothesis that collaborations, and specifically with highly innovative (knowledge-intensive) regions, positively affect the innovation performances of lagging-behind regions. Finally, the implications of EU policies for supporting lagging-behind regions are discussed.
In vertebrates, immunoglobulins (Igs), commonly known as antibodies, play an integral role in the armamentarium of immune defense against various pathogens. After an antigenic challenge, antibodies ...are secreted by differentiated B cells called plasma cells. Antibodies have two predominant roles that involve specific binding to antigens to launch an immune response, along with activation of other components of the immune system to fight pathogens. The ability of immunoglobulins to fight against innumerable and diverse pathogens lies in their intrinsic ability to discriminate between different antigens. Due to this specificity and high affinity for their antigens, antibodies have been a valuable and indispensable tool in research, diagnostics and therapy. Although seemingly a simple maneuver, the association between an antibody and its antigen, to make an antigen-antibody complex, is comprised of myriads of non-covalent interactions. Amino acid residues on the antigen binding site, the epitope, and on the antibody binding site, the paratope, intimately contribute to the energetics needed for the antigen-antibody complex stability. Structural biology methods to study antigen-antibody complexes are extremely valuable tools to visualize antigen-antibody interactions in detail; this helps to elucidate the basis of molecular recognition between an antibody and its specific antigen. The main scope of this chapter is to discuss the structure and function of different classes of antibodies and the various aspects of antigen-antibody interactions including antigen-antibody interfaces-with a special focus on paratopes, complementarity determining regions (CDRs) and other non-CDR residues important for antigen binding and recognition. Herein, we also discuss methods used to study antigen-antibody complexes, antigen recognition by antibodies, types of antigens in complexes, and how antigen-antibody complexes play a role in modern day medicine and human health. Understanding the molecular basis of antigen binding and recognition by antibodies helps to facilitate the production of better and more potent antibodies for immunotherapy, vaccines and various other applications.
Despite the uncertainty in future climate-change impacts, it is often assumed that humans would be able to adapt to any possible warming. Here we argue that heat stress imposes a robust upper limit ...to such adaptation. Peak heat stress, quantified by the wet-bulb temperature TW, is surprisingly similar across diverse climates today. TW never exceeds 31 °C. Any exceedence of 35 °C for extended periods should induce hyperthermia in humans and other mammals, as dissipation of metabolic heat becomes impossible. While this never happens now, it would begin to occur with global-mean warming of about 7 °C, calling the habitability of some regions into question. With 11-12 °C warming, such regions would spread to encompass the majority of the human population as currently distributed. Eventual warmings of 12 °C are possible from fossil fuel burning. One implication is that recent estimates of the costs of unmitigated climate change are too low unless the range of possible warming can somehow be narrowed. Heat stress also may help explain trends in the mammalian fossil record.
The costs of inter- and intra-regional diversification have been widely discussed in the existing international business literature, but the findings are mixed. Explanations for the mixed findings ...have important managerial implications, because business managers have to estimate accurately the costs of doing business within and across regions before they make their internationalization decisions. To explain the existing mixed findings, this study differentiates between liabilities of foreignness at the country and regional levels, and explores the joint effects of liability of country foreignness (LCF) and liability of regional foreignness (LRF) on the performance of internationalizing firms. Using data from 167 Canadian firms, we find that LCF may not necessarily be negatively correlated with intra-regional diversification, but LRF is positively correlated with inter-regional diversification. LCF moderates the relationship between LRF and inter-regional diversification, and also mediates the relationship between intra-regional diversification and firm performance. LRF mediates the relationship between inter-regional diversification and firm performance. Missing one or more of these variables may result in different cost estimates. Identification of the relationships between these variables helps to improve the accuracy of estimating the costs of doing business aboard.
PRKACB (Protein Kinase CAMP-Activated Catalytic Subunit Beta) is predominantly expressed in the brain, and regulation of this gene links to neuroprotective effects against tau and Aβ-induced ...toxicity. Here we studied a (GCC)-repeat spanning the core promoter and 5' UTR of this gene in 300 human subjects, consisting of late-onset neurocognitive disorder (NCD) (N = 150) and controls (N = 150). We also implemented several models to study the impact of this repeat on the three-dimensional (3D) structure of DNA. While the PRKACB (GCC)-repeat was strictly monomorphic at 7-repeats, we detected two 7/8 genotypes only in the NCD group. In all examined models, the (GCC)7 and its periodicals had the least range of divergence variation on the 3D structure of DNA in comparison to the 8-repeat periodicals and several hypothetical repeat lengths. A similar inert effect on the 3D structure was not detected in other classes of short tandem repeats (STRs) such as GA and CA repeats. In conclusion, we report monomorphism of a long (GCC)-repeat in the PRKACB gene in human, its inert effect on DNA structure, and enriched divergence in late-onset NCD. This is the first indication of natural selection for a monomorphic (GCC)-repeat, which probably evolved to function as an "epigenetic knob", without changing the regional DNA structure.
Light chain (LC) amyloidosis (AL) is a fatal disease in which immunoglobulin LC deposit as fibrils. Although the LC amyloid-forming propensity is attributed primarily to the variable region, fibrils ...also contain full-length LC comprised of variable-joining (VL) and constant (CL) regions. To assess the role of CL in fibrillogenesis, we compared the thermal stability of full-length LC and corresponding VL and CL fragments. Protein unfolding and aggregation were monitored by circular dichroism and light scattering. A full-length λ6 LC purified from urine of a patient with AL amyloidosis showed irreversible unfolding coupled to aggregation. The transition temperature decreased at slower heating rates, indicating kinetic effects. Next, we studied five recombinant λ6 proteins: full-length amyloidogenic LC, its VL, germline LC, germline VL, and CL. Amyloidogenic and germline proteins showed similar rank order of stability, VL < LC < CL; hence, in the full-length LC, VL destabilizes CL. Amyloidogenic proteins were less stable than their germline counterparts, suggesting that reduction in VL stability destabilizes the full-length LC. Thermal unfolding of the full-length amyloidogenic and germline LC required high activation energy and involved irreversible aggregation, yet the unfolding of the isolated VL and CL fragments was partially reversible. Therefore, compared to their fragments, full-length LCs are more likely to initiate aggregation during unfolding and provide a template for the VL deposition. The kinetic barrier for this aggregation is regulated by the stability of the VL region. This represents a paradigm shift in AL fibrillogenesis and suggests CL region as a potential therapeutic target.
Bayesian analysis is applied to detect changepoints in the time series of seasonal typhoon counts in the vicinity of Taiwan. An abrupt shift in the typhoon count series occurs in 2000. On average, ...3.3 typhoons per year have been noted before 2000 (1970–99), with the rate increasing to 5.7 typhoons per year since 2000 (2000–06). This abrupt change is consistent with a northward shift of the typhoon track over the western North Pacific–East Asian region and an increase of typhoon frequency over the Taiwan–East China Sea region. The northward shift of the typhoon track tends to be associated with typhoon-enhancing environmental conditions over the western North Pacific, namely, the weakening of the western North Pacific subtropical high, the strengthening of the Asian summer monsoon trough, and the enhanced positive vorticity anomalies in the lower troposphere. Based on observational analysis and model simulations, warm sea surface temperature anomalies over the equatorial western and central Pacific appear to be a major factor contributing to a northward-shifted typhoon track.
It is well known that most of the stars form in rich clusters. However, recent Spitzer observations have shown that a significant number of stars also form in the distributed mode; their origin is ...not well understood. In this work, we aim to investigate clustered and distributed modes of star formation in the W4 complex. To do so, we identified and characterized the young stellar population associated with the region using homogeneous infrared data sets obtained from the Two Micron All Sky Survey, GLIMPSE, MIPS, and Wide-field Infrared Survey Explorer surveys. We make stellar surface density and minimum spanning tree maps to identify young clusters, and use Spitzer images to identify irradiated structures, such as elephant-trunk-like structures (ETLSs) and pillars in the region. The surface density distribution of the young stellar objects (YSOs) reveals three new clusterings and ∼50% distributed protostars in the H ii region. The clusters are of low-mass nature but significantly younger than the central cluster IC 1805. We identified ∼ 38 ETLSs in the region, a majority of which consist of one or a few stars at their tips. We find that these stars are low-mass (<2 M ) YSOs, located at the outskirts (>17 pc) of the cluster IC 1805 and are part of the scattered distributed population. We argued that the star formation in the ETLSs of W4 is going on possibly due to the triggering effect of the expanding W4 bubble. Although high-resolution photometric and spectroscopic data would be required to confirm the scenario, nonetheless, we discuss the implications of this scenario for our understanding of distributed low-mass star formation in cloud complexes as opposed to other mechanisms such as turbulent fragmentation and dynamical ejection.
Much of the rising international connectedness of city-regions has developed from MNEs replacing local connections with (superior) international ones. This often creates local disconnectedness that ...energizes the current populist backlash against MNE activities. We develop approaches to new IB theory, addressing the interdependencies of MNEs and city-regions that we propose as a crucial avenue for future research. We contrast two generic MNE strategies. The first is the traditional one: the ‘global orchestration’ of resources and markets. We argue that it exacerbates local disconnectedness. The second, that we call ‘local spawning,’ involves engaging with the local entrepreneurial ecosystem to create and renew local connectedness, diffusing populist responses. Some MNEs are better able to implement a local spawning strategy, due to industry factors like innovation clock-speed, and firm characteristics like organizational path dependency. Finally, we distinguish between disconnection, which is an outcome of MNE strategy, and global disruptions, like the coronavirus (COVID-19) pandemic, which are primarily stochastic events. Addressing disconnections requires MNEs to re-orient their strategies while dealing with disruptions requires undertaking risk mitigation. We present empirical evidence from city-regions around the world to illustrate our theory.
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