摘要： Ssd1, a conserved fungal RNA-binding protein, is important in stress responses, cell division and virulence. Ssd1 is closely related to Dis3L2 of the RNase II family of nucleases, but lacks catalytic activity and likely suppresses translation of bound mRNAs. Previous studies identified RNA motifs enriched in Ssd1-associated transcripts, yet the sequence requirements for Ssd1 binding are not defined. Here, we identify precise binding sites of Ssd1 on RNA using in vivo cross-linking and cDNA analysis. These sites are enriched in 5 ' untranslated regions of a subset of mRNAs encoding cell wall proteins. We identified a conserved bipartite motif that binds Ssd1 with high affinity in vitro. Active RNase II enzymes have a characteristic, internal RNA binding path;the Ssd1 crystal structure at 1.9 angstrom resolution shows that remnants of regulatory sequences block this path. Instead, RNA binding activity has relocated to a conserved patch on the surface of the protein. Structure-guided mutations of this surface prevent Ssd1 from binding RNA in vitro and phenocopy Ssd1 deletion in vivo. These studies provide a new framework for understanding the function of a pleiotropic post-transcriptional regulator of gene expression and give insights into the evolution of regulatory and binding elements in the RNase II family.

关键词： Medical assistance   crisis communication   risk management   travel   epidemic intelligence   medical intelligence  

摘要： Introduction A crisis of ‘alternative truths’ represents a threat to global health security. Access to accurate, vetted information is now increasingly key to analysing and addressing travel risk. Yet keeping up to date with travel health can be challenging. Travellers are more at risk of health problems than non-travellers, from gastroenteritis to burnout. Workers on remote sites are particularly exposed to long-term isolation, frequently lacking relevant, accurate clinical advice at the time of medical decision-making. 1 Travel-related diseases such as Zika, Ebola or yellow fever have all been associated with misinformation campaigns. During travel, stressors are amplified, compounding information overload, which typifies the immediate aftermath of any major crisis, worsened in a pandemic when access to health advice ordinarily obtained from trusted local health services is hampered. During the Fukushima crisis for example, we received calls enquiring about the validity of taking iodised salt to prevent the aftermath of nuclear fallout....

关键词： Spray penetration   spray cone angle   injection pressure   alternative fuels   evaporation model  

摘要： Spray characteristics and transient behaviour of alternative fuel droplets at different spray cone angles, injection pressures and droplet diameters are presented, using a simple spray evaporation model. The model only considers drag force acting on the droplet. Radiation heat transfer during the evaporation process is neglected. The model incorporates temperature-dependent fuel properties, drag coefficient and Reynolds number for robustness. It is tested for alternative fuels, namely Jatropha Bio-synthetic Paraffinic Kerosen (JSPK), Camelina Bio-synthetic Paraffinic Kerosene (CSPK) and biodiesel, while Jet-A is used for comparison. The transient behaviour of fuel droplets is visualised through a time-history of the normalised squared diameter. Changes in the particles' temperature, mass, density, velocity and heat transfer coefficient over time are observed. Moreover, penetration of the fuels at different spray cone angles, injection pressures and droplet diameters is compared. Among the tested fuels, biodiesel is found to have the farthest penetration due to its high vapour pressure. Notably, increasing spray cone angle reduces penetration length. A similar trend is observed when injection pressure is increased. However, at constant injection pressure, increasing droplet diameter increases spray cone angle and spray penetration. To obtain optimum penetration, therefore, a larger cone angle should be used for fuel with high density and vapour pressure, and vice versa.

摘要： 莫言有一种能力,就是非常有效地将现实生活转化为非现实生活,没有比他小说里的现实生活更不现实了.仿佛他看世界的眼睛有一种屈光功能,景物一旦进入视野,顿时就改了面目.并不是说与原来完全不一样,甚至很一样,可就是成了另一个世界.这世界里的一切还是依原来的样式链接镶嵌,色彩却全变了,很容易将其视为一种风格,但风格其实是装饰的意味,这里的色彩则影响到事情的性质.这"色彩"更接近"质地"的意思,事情的质地不同了,于是,就变得不那么真实.在那个不真实的世界里,比真实的更为沉重,但确有着一重意境.小说实在是一种过于结实的东西,现实既是它的内核,又是外相,要从中抽离出一个独立的世界,是需要更有力量的占位.

关键词： Ozone   Decontamination   SARS-CoV-2   Protective equipment   COVID-19  

摘要： COVID-19 pandemic created a global shortage of medical protective equipment. Here, we considered ozone (O3) a disinfectant alternative due to its potent oxidative activity against biological macromolecules. The O3 decontamination assays were done using SARS-CoV-2 obtained from patients to produce artificial contamination of N95 masks and biosecurity gowns. The quantification of SARS-CoV-2 was performed before and after exposing the samples to different ozone gas concentrations for times between 5 and 30 min. Viral loads as a function of the O3 exposure time were estimated from the data obtained by the RT-PCR technique. The genetic material of the virus was no longer detected for any tested concentrations after 15 min of O3 exposure, which means a disinfection Concentration-Time above 144 ppm min. Vibrational spectroscopies were used to follow the modifications of the polymeric fibers after the O3 treatment. The results indicate that the N95 masks could be safely reused after decontamination with treatments of 15 min at the established O3 doses for a maximum of 6 cycles.

关键词： Land-use conflict   Energy system   Modeling to generate alternatives   Uncertainty   Energy transition  

摘要： Long-term power market outlooks suggest a rapid increase in renewable energy deployment as a main solution to greenhouse gas mitigation in the Northern European energy system. However, the consequential area requirement is a non-techno-economic aspect that currently is omitted by many energy system optimization models. This study applies modeling to generate alternatives (MGA) technique to the Balmorel energy system model to address spatial conflicts related to increased renewable energy deployment. The approach searches for alternative solutions that minimize land-use conflicts while meeting the low-carbon target, by allowing a 1% to 15% increase in system costs compared to the least-cost solution. Two alternative objectives are defined to reflect various aspects of spatial impact. The results show that the least-cost solution requires 1.2%-3.6% of the land in the modeled countries in 2040 for onshore wind and solar PV installations. A 10% increase in costs can reduce the required land area by 58% by relying more on offshore wind. Nuclear energy may also be an option if both onshore and offshore areas are to be reduced, or in a less flexible system. Both offshore wind and nuclear energy technologies are associated with higher risks and pose uncertainties in terms of reaching the climate targets in time. The changes in costs and required land areas imply significantly higher annual costs ranging from 200 to 750 kEUR/km2 to avoid land use for energy infrastructure. Overall, this study confirms that the energy transition strategies prioritizing land savings from energy infrastructure are feasible, but high risks and costs of averted land are involved.

关键词： Glycosylation  

摘要： Almost 60% of commercialized pharmaceutical proteins are glycosylated. Glycosylation is considered a critical quality attribute, as it affects the stability, bioactivity and safety of proteins. Hence, the development of analytical methods to characterise the composition and structure of glycoproteins is crucial. Currently, existing methods are time-consuming, expensive, and require significant sample preparation steps, which can alter the robustness of the analyses. In this work, we suggest the use of a fast, direct, and simple Fourier transform infrared spectroscopy (FT-IR) combined with a chemometric strategy to address this challenge. In this context, a database of FT-IR spectra of glycoproteins was built, and the glycoproteins were characterised by reference methods (MALDI-TOF, LC-ESI-QTOF and LC-FLR-MS) to estimate the mass ratio between carbohydrates and proteins and determine the composition in monosaccharides. The FT-IR spectra were processed first by Partial Least Squares Regression (PLSR), one of the most used regression algorithms in spectroscopy and secondly by Support Vector Regression (SVR). SVR has emerged in recent years and is now considered a powerful alternative to PLSR, thanks to its ability to flexibly model nonlinear relationships. The results provide clear evidence of the efficiency of the combination of FT-IR spectroscopy, and SVR modelling to characterise glycosylation in therapeutic proteins. The SVR models showed better predictive performances than the PLSR models in terms of RMSECV, RMSEP, R2(CV), R2(Pred) and RPD. This tool offers several potential applications, such as comparing the glycosylation of a biosimilar and the original molecule, monitoring batch-to-batch homogeneity, and in-process control.

关键词： mRNA vaccine   alternative splicing-derived cancer neoantigens   cancer immunotherapy   computational identification of cancer neoantigens  

摘要： Messenger RNA (mRNA) vaccines have shown great potential for anti-tumor therapy due to the advantages in safety, efficacy and industrial production. However, it remains a challenge to identify suitable cancer neoantigens that can be targeted for mRNA vaccines. Abnormal alternative splicing occurs in a variety of tumors, which may result in the translation of abnormal transcripts into tumor-specific proteins. High-throughput technologies make it possible for systematic characterization of alternative splicing as a source of suitable target neoantigens for mRNA vaccine development. Here, we summarized difficulties and challenges for identifying alternative splicing-derived cancer neoantigens from RNA-seq data and proposed a conceptual framework for designing personalized mRNA vaccines based on alternative splicing-derived cancer neoantigens. In addition, several points were presented to spark further discussion toward improving the identification of alternative splicing-derived cancer neoantigens.

摘要： 事后他们都记不得了,就像一团黑光漂浮在梦境里——至少周有果是这样想的. 这天下午,周有果从东北回来,叫上老同学孙无花,孙无花又叫上张小叶,三人在风吹尘扬的旧街闲逛,饶有兴致地回忆起了大学时光.毕业十年,往事就像他们眼角模糊的皱纹,在谈论了一番东北狍子、黑熊和人参后,孙、张二人又各自感慨单调乏味的家乡生活.夜色犹如黑蛾扑腾而来,几个人仿佛想起什么又无话可说,空气变得单调沉闷.周有果提议去吃小龙虾,张小叶撇撇嘴不置可否,孙无花表示赞成,事情就这么定了.大学时代,他们的行动常常也是这样.