Features of financing of small business and microenterprises

In this article, we examined the specifics of financing small businesses and microenterprises

Inhibition of SARS-CoV-2 Replication by a Small Interfering RNA Targeting the Leader Sequence

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected almost 200 million people worldwide and led to approximately 4 million deaths as of August 2021. Despite successful vaccine development, treatment options are limited. A promising strategy to specifically target viral infections is to suppress viral replication through RNA interference (RNAi). Hence, we designed eight small interfering RNAs (siRNAs) targeting the highly conserved 5′-untranslated region (5′-UTR) of SARS-CoV-2. The most promising candidate identified in initial reporter assays, termed siCoV6, targets the leader sequence of the virus, which is present in the genomic as well as in all subgenomic RNAs. In assays with infectious SARS-CoV-2, it reduced replication by two orders of magnitude and prevented the development of a cytopathic effect. Moreover, it retained its activity against the SARS-CoV-2 alpha variant and has perfect homology against all sequences of the delta variant that were analyzed by bioinformatic means. Interestingly, the siRNA was even highly active in virus replication assays with the SARS-CoV-1 family member. This work thus identified a very potent siRNA with a broad activity against various SARS-CoV viruses that represents a promising candidate for the development of new treatment options

Barents-2.5km v2.0: An operational data-assimilative coupled ocean and sea ice ensemble prediction model for the Barents Sea and Svalbard

An operational ocean and sea ice forecast model, Barents-2.5, is implemented at MET Norway for short-term forecasting at the coast off Northern Norway, the Barents Sea, and waters around Svalbard. Primary forecast parameters are the sea ice concentration (SIC), sea surface temperature (SST), and ocean currents. The model is also a substantial input for drift modeling of pollutants, ice berg, and in search-and-rescue pertinent applications in the Arctic domain. Barents-2.5 has recently been upgraded to include an Ensemble Prediction System with 24 daily realizations of the model state. SIC, SST and in-situ hydrography are constrained through the Ensemble Kalman Filter (EnKF) data assimilation scheme executed in daily forecast cycles with lead time up to 66 hours. While the ocean circulation is not directly constrained by assimilation of ocean currents, the model ensemble represents the given uncertainty in the short-term current field by retaining the current state for each member throughout forecast cycles. Here we present the model setup and a validation in terms of SIC, SST and in-situ hydrography. The performance of the ensemble to represent the models uncertainty, and the performance of the EnKF to constrain the model state are discussed, in addition to the model&rsquo;s forecast capabilities for SIC and SST.</p

A relocatable ocean model in support of environmental emergencies

During the Costa Concordia emergency case, regional, subregional, and relocatable ocean models have been used together with the oil spill model, MEDSLIK-II, to provide ocean currents forecasts, possible oil spill scenarios, and drifters trajectories simulations. The models results together with the evaluation of their performances are presented in this paper. In particular, we focused this work on the implementation of the Interactive Relocatable Nested Ocean Model (IRENOM), based on the Harvard Ocean Prediction System (HOPS), for the Costa Concordia emergency and on its validation using drifters released in the area of the accident. It is shown that thanks to the capability of improving easily and quickly its configuration, the IRENOM results are of greater accuracy than the results achieved using regional or subregional model products. The model topography, and to the initialization procedures, and the horizontal resolution are the key model settings to be configured. Furthermore, the IRENOM currents and the MEDSLIK-II simulated trajectories showed to be sensitive to the spatial resolution of the meteorological fields used, providing higher prediction skills with higher resolution wind forcing.MEDESS4MS Project; TESSA Project; MyOcean2 Projectinfo:eu-repo/semantics/publishedVersio

SET-NUP214 fusion in acute myeloid leukemia- and T-cell acute lymphoblastic leukemia-derived cell lines

<p>Abstract</p> <p>Background</p> <p><it>SET-NUP214 </it>fusion resulting from a recurrent cryptic deletion, del(9)(q34.11q34.13) has recently been described in T-cell acute lymphoblastic leukemia (T-ALL) and in one case of acute myeloid leukemia (AML). The fusion protein appears to promote elevated expression of <it>HOXA </it>cluster genes in T-ALL and may contribute to the pathogenesis of the disease. We screened a panel of ALL and AML cell lines for <it>SET-NUP214 </it>expression to find model systems that might help to elucidate the cellular function of this fusion gene.</p> <p>Results</p> <p>Of 141 human leukemia/lymphoma cell lines tested, only the T-ALL cell line LOUCY and the AML cell line MEGAL expressed the <it>SET(TAF-</it>Iβ)-<it>NUP214 </it>fusion gene transcript. RT-PCR analysis specifically recognizing the alternative first exons of the two <it>TAF-</it>I isoforms revealed that the cell lines also expressed <it>TAF-</it>Iα-<it>NUP214 </it>mRNA. Results of fluorescence in situ hybridization (FISH) and array-based copy number analysis were both consistent with del(9)(q34.11q34.13) as described. Quantitative genomic PCR also confirmed loss of genomic material between <it>SET </it>and <it>NUP214 </it>in both cell lines. Genomic sequencing localized the breakpoints of the <it>SET </it>gene to regions downstream of the stop codon and to <it>NUP214 </it>intron 17/18 in both LOUCY and MEGAL cells. Both cell lines expressed the 140 kDa SET-NUP214 fusion protein.</p> <p>Conclusion</p> <p>Cell lines LOUCY and MEGAL express the recently described <it>SET-NUP214 </it>fusion gene. Of special note is that the formation of the <it>SET </it>exon 7/<it>NUP214 </it>exon 18 gene transcript requires alternative splicing as the <it>SET </it>breakpoint is located downstream of the stop codon in exon 8. The cell lines are promising model systems for <it>SET-NUP214 </it>studies and should facilitate investigating cellular functions of the the SET-NUP214 protein.</p

Surface currents in operational oceanography: Key applications, mechanisms, and methods

This paper reviews physical mechanisms, observation techniques and modelling approaches dealing with surface currents on short time scales (hours to days) relevant for operational oceanography. Key motivations for this article include fundamental difficulties in reliable measurements and the persistent lack of a widely held consensus on the definition of surface currents. These problems are augmented by the fact that various methods to observe and model ocean currents yield very different representations of a surface current. We distinguish between four applicable definitions for surface currents; (i) the interfacial surface current, (ii) the direct wind-driven surface current, (iii) the surface boundary layer current, and (iv) an effective drift current. Finally, we discuss challenges in synthesising various data sources of surface currents - i.e. observational and modelling – and take a view on the predictability of surface currents concluding with arguments that parts of the surface circulation exhibit predictability useful in an operational context

The Origins of Lactase Persistence in Europe

Lactase persistence (LP) is common among people of European ancestry, but with the exception of some African, Middle Eastern and southern Asian groups, is rare or absent elsewhere in the world. Lactase gene haplotype conservation around a polymorphism strongly associated with LP in Europeans (−13,910 C/T) indicates that the derived allele is recent in origin and has been subject to strong positive selection. Furthermore, ancient DNA work has shown that the −13,910*T (derived) allele was very rare or absent in early Neolithic central Europeans. It is unlikely that LP would provide a selective advantage without a supply of fresh milk, and this has lead to a gene-culture coevolutionary model where lactase persistence is only favoured in cultures practicing dairying, and dairying is more favoured in lactase persistent populations. We have developed a flexible demic computer simulation model to explore the spread of lactase persistence, dairying, other subsistence practices and unlinked genetic markers in Europe and western Asia's geographic space. Using data on −13,910*T allele frequency and farming arrival dates across Europe, and approximate Bayesian computation to estimate parameters of interest, we infer that the −13,910*T allele first underwent selection among dairying farmers around 7,500 years ago in a region between the central Balkans and central Europe, possibly in association with the dissemination of the Neolithic Linearbandkeramik culture over Central Europe. Furthermore, our results suggest that natural selection favouring a lactase persistence allele was not higher in northern latitudes through an increased requirement for dietary vitamin D. Our results provide a coherent and spatially explicit picture of the coevolution of lactase persistence and dairying in Europe