Trypsin-like Inhibitor Domain (TIL)-Harboring Protein Is Essential for Aedes aegypti Reproduction

Cysteine-rich trypsin inhibitor-like domain (TIL)-harboring proteins are broadly distributed in nature but remain understudied in vector mosquitoes. Here we have explored the biology of a TIL domain-containing protein of the arbovirus vector Aedes aegypti, cysteine-rich venom protein 379 (CRVP379). CRVP379 was previously shown to be essential for dengue virus infection in Ae. aegypti mosquitoes. Gene expression analysis showed CRVP379 to be highly expressed in pupal stages, male testes, and female ovaries. CRVP379 expression is also increased in the ovaries at 48 h post-blood feeding. We used CRISPR-Cas9 genome editing to generate two mutant lines of CRVP379 with mutations inside or outside the TIL domain. Female mosquitoes from both mutant lines showed severe defects in their reproductive capability; mutant females also showed differences in their follicular cell morphology. However, the CRVP379 line with a mutation outside the TIL domain did not affect male reproductive performance, suggesting that some CRVP379 residues may have sexually dimorphic functions. In contrast to previous reports, we did not observe a noticeable difference in dengue virus infection between the wild-type and any of the mutant lines. The importance of CRVP379 in Ae. aegypti reproductive biology makes it an interesting candidate for the development of Ae. aegypti population control methods.     

The multiphysics modeling of heat and moisture induced stress and strain of historic building materials and artefacts

The basic structure of historic sites and their associated interior artefacts can be damaged or even destroyed by climate change. The evaluation of combined heat and moisture induced stress and strain (HMSS) can predict possible damage-related processes. In this paper, the development of one- and two-dimensional HMSS models of building materials and artefacts in COMSOL Multiphysics Version 4, a commercial finite element software, is presented. The validation of the numerical models is revealed using analytical, numerical and experimental solutions. As a result, the HMSS model was shown to be an adequate predictive tool to determine possible damage-related processes in building assemblies and artefacts.     

Modelling collective decision making in groups and crowds: Integrating social contagion and interacting emotions, beliefs and intentions

Collective decision making involves on the one hand individual mental states such as beliefs, emotions and intentions, and on the other hand interaction with others with possibly different mental states. Achieving a satisfactory common group decision on which all agree requires that such mental states are adapted to each other by social interaction. Recent developments in social neuroscience have revealed neural mechanisms by which such mutual adaptation can be realised. These mechanisms not only enable intentions to converge to an emerging common decision, but at the same time enable to achieve shared underlying individual beliefs and emotions. This paper presents a computational model for such processes. As an application of the model, an agent-based analysis was made of patterns in crowd behaviour, in particular to simulate a real-life incident that took place on May 4, 2010 in Amsterdam. From available video material and witness reports, useful empirical data were extracted. Similar patterns were achieved in simulations, whereby some of the parameters of the model were tuned to the case addressed, and most parameters were assigned default values. The results show the inclusion of contagion of belief, emotion, and intention states of agents results in better reproduction of the incident than non-inclusion.     

The in vitro and in vivo investigation of inhaled migraine therapies using a novel aerosol delivery system consisting of an air pressurized capsule device (APCD) in combination with a pMDI spacer for endotracheal dosing into beagle dogs

Abstract

Context: Aerosol delivery to animals in preclinical settings has historically been very challenging, requiring the use of techniques, such as intratracheal instillation and dry powder insufflation, that are somewhat invasive, inefficient and not representative of clinical inhalation.

Objective: The objective of this work is to develop a system to deliver dry powder to dogs in an efficient and effective manner for the study of new anti-migraine compounds in development.

Materials and methods: The new device uses a metered aliquot of a dry gas to force dry powder drug from a pre-filled HPMC capsule into an AeroChamber® spacer for subsequent inhalation by the animal.

Results: The delivery of two invesigational migraine drugs via the new device was assessed in vitro using abbreviated Andersen cascade impaction and showed the device is capable of generating a reproducible delivered dose of up to ～68% with more than 50% of the dose in the respirable range. In vivo studies have also been performed showing that this device effectively delivered the migraine drugs to spontaneously breathing dogs using a proprietary validated dog inhalation model.

Discussion: Results confirmed that the air pressurized capsule device (APCD) was effective in delivering the APIs to lungs of the animals. The in vivo data verified the advantages of inhaled delivery over oral delivery for this class of drugs and were used to establish the cardiopulmonary and respiratory side effect liability profile for these compounds.

Conclusions: This work has demonstrated the utility of this device for quick and accurate screening of prospective drug candidates, representing a significant improvement in ease of use and reprodicibility over current delivery methods.     

从集体利益中产生个人利益——共鸣设计方法及其在独立住宅转化为集合住宅中的运用

提出可以增加集合住宅受欢迎度的共鸣设计方法策略,这些策略不仅考虑到建筑本身的一些可能性,同时考虑到在空间和社会环境方面的要求,涵盖了物理的、心理的以及社会的因素;指出这类策略的应用带来了高度的用户接受度并使得适应性建筑在一个长时期内可以保持其价值.阐释在设计方法的帮助下,建筑物被记录和相互比较.