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We perform a statistical analysis of deterministic energy-decreasing algorithms on mean-field spin models with complex energy landscape like the Sine model and the Sherrington Kirkpatrick model. We specifically address the following question: in the search of low energy configurations is it convenient (and in which sense) a quick decrease along the gradient (greedy dynamics) or a slow decrease close to the level curves (reluctant dynamics)? Average time and wideness of the attraction basins are introduced for each algorithm together with an interpolation among the two and experimental results are presented for different system sizes. We found that while the reluctant algorithm performs better for a fixed number of trials, the two algorithms become basically equivalent for a given elapsed time due to the fact that the greedy has a shorter relaxation time which scales linearly with the system size compared to a quadratic dependence for the reluctant. Comment: 20 pages, 6 figures. New version, to appear on J.Phys.A

Coupled processes between the equatorial ocean and atmosphere control the spatial structure of the annual mean state in the Pacific region,in particular the warm-pool/cold- tongue structure.At the same time,coupled processes are known to be responsible for the variability about this mean state,in particular the El-Niño/Southern-Oscillation phe- nomenon.In this paper,we consider the connection between both effects of coupling by investigating the linear stability of fully coupled climatologies in an intermediate coupled model.The new element here is that when parameters-such as the coupling strength-are changed,the potential amplification of disturbances can be greatly influenced by a simul- taneous modification of the mean state.This alters the stability properties of the coupled climatology,relative to the flux-corrected cases that have been previously studied.It ap- pears possible to identify a regime in parameter space where ENSO-like unstable modes coincide with a reasonable warm-pool/cold-tongue structure.These unstable modes are mixed SST/ocean-dynamics modes,that is,they arise through an interaction of oscillatory modes originating from ocean dynamics and oscillatory SST-modes.These effects are qual- itatively similar in this fully coupled problem compared to the ?ux-corrected problem,but the sensitivity of the ENSO mode to parameters and external variations is larger due to feedbacks in the climatology.

Abstract Background Coronaviruses pose a serious threat to global health as evidenced by Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and COVID-19. SARS Coronavirus (SARS-CoV), MERS Coronavirus (MERS-CoV), and the novel coronavirus, previously dubbed 2019-nCoV, and now officially named SARS-CoV-2, are the causative agents of the SARS, MERS, and COVID-19 disease outbreaks, respectively. Safe vaccines that rapidly induce potent and long-lasting virus-specific immune responses against these infectious agents are urgently needed. The coronavirus spike (S) protein, a characteristic structural component of the viral envelope, is considered a key target for vaccines for the prevention of coronavirus infection. Methods We first generated codon optimized MERS-S1 subunit vaccines fused with a foldon trimerization domain to mimic the native viral structure. In variant constructs, we engineered immune stimulants (RS09 or flagellin, as TLR4 or TLR5 agonists, respectively) into this trimeric design. We comprehensively tested the pre-clinical immunogenicity of MERS-CoV vaccines in mice when delivered subcutaneously by traditional needle injection, or intracutaneously by dissolving microneedle arrays (MNAs) by evaluating virus specific IgG antibodies in the serum of vaccinated mice by ELISA and using virus neutralization assays. Driven by the urgent need for COVID-19 vaccines, we utilized this strategy to rapidly develop MNA SARS-CoV-2 subunit vaccines and tested their pre-clinical immunogenicity in vivo by exploiting our substantial experience with MNA MERS-CoV vaccines. Findings Here we describe the development of MNA delivered MERS-CoV vaccines and their pre-clinical immunogenicity. Specifically, MNA delivered MERS-S1 subunit vaccines elicited strong and long-lasting antigen-specific antibody responses. Building on our ongoing efforts to develop MERS-CoV vaccines, promising immunogenicity of MNA-delivered MERS-CoV vaccines, and our experience with MNA fabrication and delivery, including clinical trials, we rapidly designed and produced clinically-translatable MNA SARS-CoV-2 subunit vaccines within 4 weeks of the identification of the SARS-CoV-2 S1 sequence. Most importantly, these MNA delivered SARS-CoV-2 S1 subunit vaccines elicited potent antigen-specific antibody responses that were evident beginning 2 weeks after immunization. Interpretation MNA delivery of coronaviruses-S1 subunit vaccines is a promising immunization strategy against coronavirus infection. Progressive scientific and technological efforts enable quicker responses to emerging pandemics. Our ongoing efforts to develop MNA-MERS-S1 subunit vaccines enabled us to rapidly design and produce MNA SARS-CoV-2 subunit vaccines capable of inducing potent virus-specific antibody responses. Collectively, our results support the clinical development of MNA delivered recombinant protein subunit vaccines against SARS, MERS, COVID-19, and other emerging infectious diseases.

SAMENVATTING Het woord spiaggia ‘strand’ wordt besproken binnen het veld van woorden die een scheiding tussen land en water aangeven. Hierbij worden historisch verschillende scenario’s (frames) onderscheiden, al naar de functie de het strand destijds had. Spiaggia wordt vergeleken met zijn synoniemen; alle voorbeelden stammen uit het corpusmateriaal van de LIZ. Speciale aandacht wordt besteed aan de relatie tussen woord en referent. Ten slotte wordt de historie van de uitdrukking ultima spiaggia beschreven. RIASSUNTO Si discute la parola spiaggia all’interno del campo delle parole che indicano la separazione tra terra e acqua. Facendo questo si distinguono quattro scenari, che differiscono secondo la funzione della spiaggia nel periodo in questione. La parola spiaggia si confronta con i suoi sinonimi; tutti gli esempi vengono dal corpus della LIZ. Si dedica un’attenzione speciale alla relazione tra parola e referente. Infine si descrive la storia dell’espressione ultima spiaggia. SUMMARY The word spiaggia ‘beach’ is discussed within the field of words indicating the separation of land and water. Four different frames (scenario’s) are distinguished, according to the function of the beach in the different periods. The word spiaggia is confronted with its synonyms; all examples come from the materials of the LIZ-corpus. Special attention is given to the relation between words and referents. Finally there is a discussion of the history of the expression ultima spiaggia.

In this article we describe our recent efforts in the area of palladium- and nickel-catalysed aromatic substitution reactions. Main focus is on low cost and low waste production methods. The use of aromatic carboxylic anhydrides in the Heck reaction leads to a waste-free protocol. In addition these reactions are easy to work up as no ligands or bases are used. For Heck reactions where substrates or products do not tolerate high temperatures we found that use of a bulky phosphoramidite as ligand for palladium leads to a very fast reaction at low temperatures. Recycle of palladium in ligand-free Heck and Suzuki reactions is easily accomplished by treating the palladium black that precipitates at the end of the reaction on a carrier material with a small excess of I2 prior to its re-use in the next run. Use of aryl chlorides in the palladium- and nickel-catalysed formation of biaryls can be accomplished by using the nickel-catalysed coupling with arylzinc chlorides. Better still, it was possible to make use of the arylgrignard and use a catalytic amount of ZnCl2. Whereas the strength of these aromatic substitution reactions lies in their broad tolerance of functional groups, one exception was the Sonogashira reaction on 3-bromoaniline. The problem was solved by making use of in situ catalytic protection of the NH2 group with benzaldehyde.

This study combines historical data and the principles of bone functional adaptation to examine variation in terrestrial mobility in men and women from pre-industrial urban (Alkmaar 7M, 9F) and rural (Klaaskinderkerke 12M, 8F; Middenbeemster 21M, 22F) Dutch populations. Cross-sectional properties of the femoral and tibial midshaft are determined to investigate variation in lower limb mechanical loading. All populations had comparable age ranges. Rural Middenbeemster males had significantly more elliptically shaped tibiae compared to the other populations. Rural males from Klaaskinderkerke had significantly greater femoral cross-sectional area and torsional rigidity compared to females. In the tibia, the males from both rural populations had greater torsional rigidity and cross-sectional area compared to females. In the rural Middenbeemster population the males also had significantly more elliptically shaped tibiae compared to females. While no sexual dimorphism was found in the urban Alkmaar, significantly greater variation in lower limb cross-sectional properties was found for both males and females relative to the rural populations. These results conform to predictions based on the historical literature of greater lower limb loading in rural males compared to females as well as a greater variety of tasks performed in urban environments. The lack of significant differences in lower limb torsional rigidity or shape between populations in either sex suggests that rural life was not necessarily more physically strenuous than urban life in pre-industrial Dutch populations. However, variation in sexual dimorphism suggests that labor between males and females was differently organized in the rural and urban samples.

In november 1996 zijn verkiezingen gehouden in de Verenigde Staten. Uiteraard werden die gewonnen door de zittende president Bill Clinton. Dit ondanks vele beschuldigingen, onder andere van sexuele intimidatie. Ook speaker New Gingrich werd onlangs herkozen, ondanks vermeende belastingfraude. De Amerikanen zijn nog nooit zo ontevreden geweest over de politiek en toch lijken ze de nieuwe termijnen van beide politici te accepteren.