Drivers for international innovation activities in developed and emerging countries

This paper aims to shed light on firm specific drivers that lead firms to internationalise their innovation activities. The paper draws a comprehensive picture of driving forces by including firm capabilities, characteristics of the firm’s competitive environment and the influence of innovation obstacles in the home country. In particular, the role of the potential driving forces is tested on the probability to carry out different innovative activities abroad (R&D, design/conception of new products, manufacturing of innovative products and implementation of new processes). In a second step these driving forces are used to observe their impact on the decision to locate innovation activities in various countries and regions (China, Eastern Europe, Western Europe and North America) as well as in groups of countries with similar levels of knowledge (country clubs). The analysis is based on the Mannheim Innovation Panel survey which represents the German CIS (Community Innovation Survey) contribution. Two survey waves are combined and result in a sample of about 1400 firms. The results show that the decision to perform innovation activities abroad is mainly driven by organisational capabilities such as absorptive capacities, international experience and existing technological competences of the respective firm. Innovation barriers at the German home base such as lack of labour and high innovation costs foster the set up of later-stage innovation activities abroad while the lack of demand demonstrates a barrier to the internationalisation decision for the development and manufacturing of new products. Location decisions receive the strongest influencing effects from the international experience of the firm. Firms which innovate in developing countries seem to require a more extensive level of international experience by international R&D cooperation

Biogeographical survey of soil microbiomes across sub-Saharan Africa:structure, drivers, and predicted climate-driven changes

BACKGROUND: Top-soil microbiomes make a vital contribution to the Earth’s ecology and harbor an extraordinarily high biodiversity. They are also key players in many ecosystem services, particularly in arid regions of the globe such as the African continent. While several recent studies have documented patterns in global soil microbial ecology, these are largely biased towards widely studied regions and rely on models to interpolate the microbial diversity of other regions where there is low data coverage. This is the case for sub-Saharan Africa, where the number of regional microbial studies is very low in comparison to other continents. RESULTS: The aim of this study was to conduct an extensive biogeographical survey of sub-Saharan Africa’s top-soil microbiomes, with a specific focus on investigating the environmental drivers of microbial ecology across the region. In this study, we sampled 810 sample sites across 9 sub-Saharan African countries and used taxonomic barcoding to profile the microbial ecology of these regions. Our results showed that the sub-Saharan nations included in the study harbor qualitatively distinguishable soil microbiomes. In addition, using soil chemistry and climatic data extracted from the same sites, we demonstrated that the top-soil microbiome is shaped by a broad range of environmental factors, most notably pH, precipitation, and temperature. Through the use of structural equation modeling, we also developed a model to predict how soil microbial biodiversity in sub-Saharan Africa might be affected by future climate change scenarios. This model predicted that the soil microbial biodiversity of countries such as Kenya will be negatively affected by increased temperatures and decreased precipitation, while the fungal biodiversity of Benin will benefit from the increase in annual precipitation. CONCLUSION: This study represents the most extensive biogeographical survey of sub-Saharan top-soil microbiomes to date. Importantly, this study has allowed us to identify countries in sub-Saharan Africa that might be particularly vulnerable to losses in soil microbial ecology and productivity due to climate change. Considering the reliance of many economies in the region on rain-fed agriculture, this study provides crucial information to support conservation efforts in the countries that will be most heavily impacted by climate change. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40168-022-01297-w

High-Affinity Inhibitors of Human NAD+-Dependent 15-Hydroxyprostaglandin Dehydrogenase: Mechanisms of Inhibition and Structure-Activity Relationships

BACKGROUND: 15-Hydroxyprostaglandin dehydrogenase (15-PGDH, EC 1.1.1.141) is the key enzyme for the inactivation of prostaglandins, regulating processes such as inflammation or proliferation. The anabolic pathways of prostaglandins, especially with respect to regulation of the cyclooxygenase (COX) enzymes have been studied in detail; however, little is known about downstream events including functional interaction of prostaglandin-processing and -metabolizing enzymes. High-affinity probes for 15-PGDH will, therefore, represent important tools for further studies. PRINCIPAL FINDINGS: To identify novel high-affinity inhibitors of 15-PGDH we performed a quantitative high-throughput screen (qHTS) by testing >160 thousand compounds in a concentration-response format and identified compounds that act as noncompetitive inhibitors as well as a competitive inhibitor, with nanomolar affinity. Both types of inhibitors caused strong thermal stabilization of the enzyme, with cofactor dependencies correlating with their mechanism of action. We solved the structure of human 15-PGDH and explored the binding modes of the inhibitors to the enzyme in silico. We found binding modes that are consistent with the observed mechanisms of action. CONCLUSIONS: Low cross-reactivity in screens of over 320 targets, including three other human dehydrogenases/reductases, suggest selectivity of the present inhibitors for 15-PGDH. The high potencies and different mechanisms of action of these chemotypes make them a useful set of complementary chemical probes for functional studies of prostaglandin-signaling pathways. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S2

Anchored enrichment dataset for true flies (order Diptera) reveals insights into the phylogeny of flower flies (family Syrphidae)

Background: Anchored hybrid enrichment is a form of next-generation sequencing that uses oligonucleotide probes to target conserved regions of the genome flanked by less conserved regions in order to acquire data useful for phylogenetic inference from a broad range of taxa. Once a probe kit is developed, anchored hybrid enrichment is superior to traditional PCR-based Sanger sequencing in terms of both the amount of genomic data that can be recovered and effective cost. Due to their incredibly diverse nature, importance as pollinators, and historical instability with regard to subfamilial and tribal classification, Syrphidae (flower flies or hoverflies) are an ideal candidate for anchored hybrid enrichment-based phylogenetics, especially since recent molecular phylogenies of the syrphids using only a few markers have resulted in highly unresolved topologies. Over 6200 syrphids are currently known and uncovering their phylogeny will help us to understand how these species have diversified, providing insight into an array of ecological processes, from the development of adult mimicry, the origin of adult migration, to pollination patterns and the evolution of larval resource utilization. Results: We present the first use of anchored hybrid enrichment in insect phylogenetics on a dataset containing 30 flower fly species from across all four subfamilies and 11 tribes out of 15. To produce a phylogenetic hypothesis, 559 loci were sampled to produce a final dataset containing 217,702 sites. We recovered a well resolved topology with bootstrap support values that were almost universally >95 %. The subfamily Eristalinae is recovered as paraphyletic, with the strongest support for this hypothesis to date. The ant predators in the Microdontinae are sister to all other syrphids. Syrphinae and Pipizinae are monophyletic and sister to each other. Larval predation on soft-bodied hemipterans evolved only once in this family. Conclusions: Anchored hybrid enrichment was successful in producing a robustly supported phylogenetic hypothesis for the syrphids. Subfamilial reconstruction is concordant with recent phylogenetic hypotheses, but with much higher support values. With the newly designed probe kit this analysis could be rapidly expanded with further sampling, opening the door to more comprehensive analyses targeting problem areas in syrphid phylogenetics and ecology.Peer reviewe

Assay platform for clinically relevant metallo-beta-lactamases

Metallo-β-lactamases (MBLs) are a growing threat to the use of almost all clinically used β-lactam antibiotics. The identification of broad-spectrum MBL inhibitors is hampered by the lack of a suitable screening platform, consisting of appropriate substrates and a set of clinically relevant MBLs. We report procedures for the preparation of a set of clinically relevant metallo-β-lactamases (i.e., NDM-1 (New Delhi MBL), IMP-1 (Imipenemase), SPM-1 (São Paulo MBL), and VIM-2 (Verona integron-encoded MBL)) and the identification of suitable fluorogenic substrates (umbelliferone-derived cephalosporins). The fluorogenic substrates were compared to chromogenic substrates (CENTA, nitrocefin, and imipenem), showing improved sensitivity and kinetic parameters. The efficiency of the fluorogenic substrates was exemplified by inhibitor screening, identifying 4-chloroisoquinolinols as potential pan MBL inhibitors

Corrigendum to: “Measurement of the tt ̄ production cross-section using eμ events with b-tagged jets in pp collisions at √s = 13 TeV with the ATLAS detector” [Phys. Lett. B 761 (2016) 136–157]

This paper describes a measurement of the inclusive top quark pair production cross-section (sigma(t (t) over bar)) with a data sample of 3.2fb(-1)of proton-proton collisions at a centre-of-mass energy of root s= 13TeV, collected in 2015 by the ATLAS detector at the LHC. This measurement uses events with an opposite-charge electron-muon pair in the final state. Jets containing b-quarks are tagged using an algorithm based on track impact parameters and reconstructed secondary vertices. The numbers of events with exactly one and exactly two b-tagged jets are counted and used to determine simultaneously sigma(t (t) over bar) and the efficiency to reconstruct and b-tag a jet from a top quark decay, thereby minimising the associated systematic uncertainties. The cross-section is measured to be:sigma(t (t) over bar) = 818 +/- 8 (stat) +/- 27 (syst) +/- 19 (lumi) +/- 12 (beam) pb,where the four uncertainties arise from data statistics, experimental and theoretical systematic effects, the integrated luminosity and the LHC beam energy, giving a total relative uncertainty of 4.4%. The result is consistent with theoretical QCD calculations at next-to-next-to-leading order. A fiducial measurement corresponding to the experimental acceptance of the leptons is also presented

A search for an unexpected asymmetry in the production of e+μ− and e−μ+ pairs in proton-proton collisions recorded by the ATLAS detector at root s = 13 TeV

This search, a type not previously performed at ATLAS, uses a comparison of the production cross sections for e(+)mu(-) and e(-)mu(+) pairs to constrain physics processes beyond the Standard Model. It uses 139 fb(-1) of proton-proton collision data recorded at root s = 13 TeV at the LHC. Targeting sources of new physics which prefer final states containing e(+)mu(-) and e(-)mu(+), the search contains two broad signal regions which are used to provide model-independent constraints on the ratio of cross sections at the 2% level. The search also has two special selections targeting supersymmetric models and leptoquark signatures. Observations using one of these selections are able to exclude, at 95% confidence level, singly produced smuons with masses up to 640 GeV in a model in which the only other light sparticle is a neutralino when the R-parity-violating coupling lambda(23)(1)' is close to unity. Observations using the other selection exclude scalar leptoquarks with masses below 1880 GeV when g(1R)(eu) = g(1R)(mu c) = 1, at 95% confidence level. The limit on the coupling reduces to g(1R)(eu) = g(1R)(mu c) = 0.46 for a mass of 1420 GeV

Measurement of the nuclear modification factor for muons from charm and bottom hadrons in Pb+Pb collisions at 5.02 TeV with the ATLAS detector

Heavy-flavour hadron production provides information about the transport properties and microscopic structure of the quark-gluon plasma created in ultra-relativistic heavy-ion collisions. A measurement of the muons from semileptonic decays of charm and bottom hadrons produced in Pb+Pb and pp collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV with the ATLAS detector at the Large Hadron Collider is presented. The Pb+Pb data were collected in 2015 and 2018 with sampled integrated luminosities of 208 mu b(-1) and 38 mu b(-1), respectively, and pp data with a sampled integrated luminosity of 1.17 pb(-1) were collected in 2017. Muons from heavy-flavour semileptonic decays are separated from the light-flavour hadronic background using the momentum imbalance between the inner detector and muon spectrometer measurements, and muons originating from charm and bottom decays are further separated via the muon track's transverse impact parameter. Differential yields in Pb+Pb collisions and differential cross sections in pp collisions for such muons are measured as a function of muon transverse momentum from 4 GeV to 30 GeV in the absolute pseudorapidity interval vertical bar eta vertical bar < 2. Nuclear modification factors for charm and bottom muons are presented as a function of muon transverse momentum in intervals of Pb+Pb collision centrality. The bottom muon results are the most precise measurement of b quark nuclear modification at low transverse momentum where reconstruction of B hadrons is challenging. The measured nuclear modification factors quantify a significant suppression of the yields of muons from decays of charm and bottom hadrons, with stronger effects for muons from charm hadron decays

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p