BK polyomavirus (BKPyV) causes a lifelong chronic infection and is associated with debilitating disease in kidney transplant recipients. Despite its importance, aspects of the virus life cycle remain poorly understood. In addition to the structural proteins, the late region of the BK genome encodes for an auxiliary protein called agnoprotein. Studies on other polyomavirus agnoproteins have suggested that the protein may contribute to virion infectivity. Here, we demonstrate an essential role for agnoprotein in BK virus release. Viruses lacking agnoprotein do not propagate to wild-type levels and fail to release from host cells. Despite this, loss of agnoprotein does not impair virion infectivity or morphogenesis. Instead, agnoprotein expression correlates with nuclear egress of BK virions. We demonstrate that the agnoprotein binding partner α-SNAP is necessary for BK virion release, and siRNA knockdown of α-SNAP prevents nuclear release of wild-type BK virions. These data highlight a novel role for agnoprotein and begin to reveal the mechanism by which polyomaviruses leave an infected cell.

Prior to lockdown the spread of COVID-19 in UK is found to be exponential, with an exponent α=0.207 In case of COVID-19 this spreading patterns is quantitatively better described with mobility-driven SIR-SEIR model [2] rather than the homogenous mixing models Lockdown has dramatically slowed down the spread of COVID-19 in UK, and even more significantly has changed the growth in the total number of infected from exponential to quadratic. This significant change is due a transition from a mobility-driven epidemic spreading to a spatial epidemic which is dominated by slow growth of spatially isolated clusters of infected population. Our results strongly indicated that, to avoid a return to exponential growth of COVID-19 (also known as “second wave”) mobility restrictions should not be prematurely lifted. Instead mobility should be kept restricted while new measures, such as wearing mask and contact tracing, get implemented in order to allow a safe exit from lockdown.

We consider a discrete-time random walk (xt) which at random times is reset to the starting position and performs a deterministic motion between them. We show that the quantity Prxt+1=n+1|xt=n,n→∞ determines if the system is averse, neutral or inclined towards resetting. It also classifies the stationary distribution. Double barrier probabilities, first passage times and the distribution of the escape time from intervals are determined.

Small molecules that can modulate or stabilize cell-cell interactions are valuable tools for investigating the impact of collective cell behavior on various biological processes such as development/morphogenesis, tissue regeneration and cancer progression. Recently, we showed that budesonide, a glucocorticoid widely used as anti-asthmatic drug, is a potent regulator of stem cell pluripotency. Here we tested the effect of different budesonide derivatives and identified CHD-030498 as a more effective analogue of budesonide. CHD-030498 was able to prevent stem cell pluripotency exit in different cell-based models, including embryonic stem-to-mesenchymal transition, spontaneous differentiation and 3D gastruloid development, and at lower doses compared to budesonide.

At the beginning of 2020, with the onset of the pandemic, the traditional learning environment for learners drastically changed globally. Since then, most students/teachers have started and practiced distance and virtual learning/teaching. Thus, a technological breakthrough in virtual learning has followed. In connection with this, many countries worldwide have commenced allocating additional financing and funds for educational institutions' technological improvement and development. The long-term stay in distance learning has revealed and highlighted new problems students face: their knowledge level has decreased, they lack socialization skills, and they face psychological and physical health problems. Due to this negative impact on students, a need to research and evaluate how much the EU countries allocated to solve the distance learning-caused problems and what programs or models they prepared has emerged and encouraged further studies. The research has found that many countries increased their allocations very minimally, e.g., 0.0.1%, but some increased their available budgets to 32%. Notably, most countries did not separate distance learning exit funding from distance learning preparation funding. Based on the problems the countries saw, only a few states identified withdrawal from distance learning as a problem. Considering this, we set ourselves the goal to evaluate exit models from distance learning and allocated funding amounts. The following objectives were planned to achieve the goal: · to evaluate the global practice of exit from distance learning; · to determine the scope of funding for pandemic management; · to evaluate the amounts of funding allocated to manage pandemic-caused consequences and the GDP ratio. Research methods: mathematical-statistical analysis, empirical analysis, and analysis of scientific literature.

Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds a great promise for regenerative medicine and has been studied in several major directions. However, cell-cycle regulation, a fundamental biological process, has not been investigated during iCM-reprogramming. Here, our time-lapse imaging on iCMs, reprogrammed by Gata4, Mef2c, and Tbx5 (GMT) monocistronic retroviruses, revealed that iCM-reprogramming was majorly initiated at late-G1- or S-phase and nearly half of GMT-reprogrammed iCMs divided soon after reprogramming. iCMs exited cell cycle along the process of reprogramming with decreased percentage of EdU⁺/αMHC-GFP⁺ cells. S-phase synchronization post-GMT-infection could enhance cell-cycle exit of reprogrammed iCMs and yield more GFP^high iCMs, which achieved an advanced reprogramming with more expression of cardiac genes than GFP^low cells; however, S-phase synchronization didn’t enhance the polycistronic-MGT reprogramming, in which cell-cycle exit had been accelerated. In conclusion, post-infection synchronization of S-phase facilitated the early progression of GMT-reprogramming through a mechanism of enhanced cell-cycle exit.

PHA synthases (PhaC) are grouped into four classes based on the kinetics and mechanisms of reaction. The grouping of PhaC enzymes into four classes is dependent on substrate specificity, according to the preference in forming short chain length (scl) or medium chain length (mcl) polymers: class I, class III, and class IV produce scl-PHAs depending on propionate, butyrate, valerate and hexanoate precursors, while class II phaC synthesize mcl-PHAs based on the alkane (C6 to C14) precursors. PHA synthases of class I, in particular PhaC_Cs from Chromobacterium USM2 and PhaC_Cn/RePhaC1 from Cupriavidus necator/R. eutropha, have been analysed and the crystal structures of the C-domains have been determined. PhaC_Cn/RePhaC1 was also studied by small angle X-ray scattering (SAXS) analysis. Models have been proposed for dimerization, catalysis mechanism, substrate recognition and affinity, product formation and product egress route. The assays based on amino acid substitution by mutagenesis have been useful to validate the hypothesis on the role of amino acids in catalysis and in accommodation of bulky substrates, for the synthesis of PHB co-polymers and medium chain length-PHA polymers with optimized chemical properties.

The entry and exit method is a simple and practical method to determine the critical slip surface of slope. However, it has the drawback of sacrificing computational efficiency to improve search accuracy. To solve this problem, this paper proposes an improved entry and exit method to search for the critical slip surface. Based on the random fields generated by using Karhunen–Loève expansion method, the simplified Bishop’s method combined with the improved entry and exit method is used to determine the critical slip surface and its corresponding minimum factor of safety. Then, the failure probability is calculated by conducting Monte Carlo simulation. Two examples are reanalyzed to verify the accuracy and efficiency of the proposed method. Meaningful comparisons are made to demonstrate the calculating accuracy and calculating efficiency of the improved entry and exit method in searching for the minimum safety factor of slope, based on which the effect of the reduced searching range on slope reliability was explored. The results indicate that the proposed method provides a practical tool for evaluating the reliability of slopes in spatially variable soils. It can greatly improve the computational efficiency in relatively high-computational accuracy of slope reliability analysis.

During normal ageing, physical changes take place, namely in terms of the biomechanical, musculoskeletal, and psychomotor systems, that reduce strength, flexibility, motor coordination, balance, and precision of movements. This article analyses the motion behaviour of a sample of 49 senior and pre-senior subjects during the process of entry to (ingress) and exit from (egress) new car models not experienced before, obtained over five days at the Geneva International Motor Show. The methodological process is based on visual studies using photography and video to analyse motion behaviour. This investigation identifies five entry movement strategies and three exit movement strategies in three types of vehicle groups. The movements adopted in the egress of the vehicle were more complex and difficult, in general, than those observed for ingress, requiring greater flexibility, agility/dexterity, and physical strength of subjects, involving more contact or support with vehicle parts. The main factor that influences movement strategies is essentially related to subjects’ levels of physical capacity and previous experiences. In conclusion, there are no significant changes in the subjects’ somatic movement strategies based on vehicle types.

The amendment or removal of superfluous government support policies is typically difficult, yet in the ever more important debate on low-carbon (i.e. clean) marine energy policy under the international law of climate action, the law of the sea, and international investment protection, there are additional dimensions of legal or economic peril. Coastal states enact policies subsidising clean energy investments, such as offshore wind energy generation, in their exclusive economic zones or continental shelves. Investors are attracted to the prospect that policies granting subsidies for ostensibly new industries are sufficiently durable. Are such subsidy policies salient or stale? In principle, the purpose of regulatory policy is the promotion of social welfare, and hence there is an optimal incidence, magnitude, and duration of the subsidy, in essence, an ideal strategy for starting, altering, or exiting such policy. We aim to introduce the concept of optimisation to the design and implementation of regulatory policy in this context. Our contribution is to offer three maxims of optimal clean marine energy law and policy: the efficiency and equity of alternative regulatory arrangements; the continuous optimisation of such arrangements; and the recognition of linguistic entanglements in the law. We test these maxims against the case of clean marine energy policy on offshore wind energy generation. One legal implication for international investment protection is that coastal states should establish a policy exit clause in their investment contracts. Our analysis of policy optimisation is generalisable across policies supporting the transition to sustainable energy forms.