Modeling the protonation states of β-secretase binding pocket by molecular dynamics simulations and docking studies

β-secretase (BACE1) is an aspartyl protease that processes the β-amyloid peptide in the human brain in patients with Alzheimer’s disease. There are two catalytic aspartates (ASP32 and ASP228) in the active domain of BACE1. Although it is believed that the net charge of the Asp dyad is −1, the exact protonation state still remains a matter of debate. We carried out molecular dynamic (MD) simulations for the four protonation states of BACE1 proteins. We applied Glide docking studies to 21 BACE1 inhibitors against the MD extracted conformations. The dynamic results infer that the protein/ligand complex remains stable during the entire simulation course for HD32D228 model. The results show that the hydrogen bonds between the inhibitor and the Asp dyad are maintained in the 10,000th ps snapshot of HD32D228 model. Our results also reveal the significant loop residues in maintaining the active binding conformation in the HD32D228 model. Molecular docking results show that the HD32D228 model provided the best enrichment factor score, suggesting that this model was able to recognize the most active compounds. Our observations provide an evidence for the preference of the anionic state (HD32D228) in BACE1 binding site and are in accord with reported computational data. The protonation state study would provide significant information to assign the correct protonation state for structure-based drug design and docking studies targeting the BACE1 proteins as a tactic to develop potential AD inhibitors.     

Cooperation in the evolutionary iterated prisoner’s dilemma game with risk attitude adaptation

The Iterated Prisoner’s Dilemma (IPD) game has been commonly used to investigate the cooperation among competitors. However, most previous studies on the IPD focused solely on maximizing players’ average payoffs without considering their risk preferences. By introducing the concept of income stream risk into the IPD game, this paper presents a novel evolutionary IPD model with agents seeking to balance between average payoffs and risks with respect to their own risk attitudes. We build a new IPD model of multiple agents, in which agents interact with one another in the pair-wise IPD game while adapting their risk attitudes according to their received payoffs. Agents become more risk averse after their payoffs exceed their aspirations, or become more risk seeking after their payoffs fall short of their aspirations. The aspiration levels of agents are determined based on their historical self-payoff information or the payoff information of the agent population. Simulations are conducted to investigate the emergence of cooperation under these two comparison methods. Results indicate that agents can sustain a highly cooperative equilibrium when they consider only their own historical payoffs as aspirations (called historical comparison) in adjusting their risk attitudes. This holds true even for the IPD with a short game encounter, for which cooperation was previously demonstrated difficult. However, when agents evaluate their payoffs in comparison with the population average payoff (called social comparison), those agents with payoffs below the population average tend to be dissatisfied with the game outcomes. This dissatisfaction will induce more risk-seeking behavior of agents in the IPD game, which will constitute a strong deterrent to the emergence of mutual cooperation in the population.     

男装品牌研发竞争力评价指标体系研究

男装品牌研发竞争力的认知与管理是品牌实力强化运作中的关键。男装品牌研发竞争力的内容包括:研发投入、研发人才与研发形象、研发模式、研发待遇与政策等,其评价指标体系的认知及其构建是研究和讨论的重点。该系列研究成果将促使男装企业提升品牌认知水平和发展管理意识,更加理解品牌研发运作和竞争力管理的重要性,最终全面理解并重视应用研发竞争力的提升途径和方式方法。     

纳米压痕法研究单晶Al3Sc相的硬度和杨氏模量

使用EBSD和纳米压痕法研究毫米级块状单晶Al₃Sc对应的取向、硬度和杨氏模量。试验结果表明,选用过共晶Al-Sc合金加热至液态后缓慢冷却(60 ℃/h)可以得到毫米级单晶Al₃Sc,通过EBSD和纳米压痕法得到五个不同取向(567)、(139)、(124)、(113)和(144)单晶Al₃Sc的硬度在3.7~4.3 GPa,复合弹性响应模量在143.6~146.1 GPa。对比不同泊松比下各取向的杨氏模量理论值与试验值,发现泊松比为0.188时二者之间差异最小,对应各取向的杨氏模量试验值在157.5~160.6 GPa。     

‘Resistance was futile!’ Cycling’s discourses of resistance to UK automobile modernism 1950–1970

This paper investigates the place of utility cycling (cycling as a means of transport rather than as a sport or leisure activity) under urban modernism in the UK. In many western contexts the dominant feature of urban modernism was its emphasis on accommodating private vehicles to the neglect of other forms of mobility. The result was the production of a ‘car-system’ with significant change to urban and rural environments. This paper assesses resistance to what we term ‘automobile modernism’ during the high watermark of its planning and implementation (1950–1970), using the UK Cyclists’ Touring Club (now known as Cycling UK) archive. We make three contributions. First, and primarily, we highlight how cycling advocacy contested automobile modernism’s claim that cycling was ‘outmoded’. In so doing we note significant continuity in policy debates and political advocacy regarding cycling’s place in the road environment around issues such as segregation from motor vehicles. Contemporary attempts to promote cycling, as well as a wider urban sustainability agenda, are heavily influenced by this history. Second, we highlight a commonality between cycling and other resistance to automobile modernism in terms of rural and urban landscape impacts. Third, we highlight how the CTC ‘professionalized’ its advocacy to resist automobile modernism.     

早冠丝瓜406新品种的选育

早冠丝瓜406是以S4为母本、X06为父本配制而成的一代杂种.极早熟,植株主蔓分枝性强,生长性强盛;雌花节位低,首朵雌花着生于主蔓第5节~7节,采收期为播种后58 d^60 d开始;嫩瓜呈长棒形,果端较圆,果皮深绿色,单果重0.5 kg^0.9 kg,果实纵径42 cm^50 cm,横径3.7 cm^4.2 cm,前期产量为16772.0 kg/hm^2,总产量可达47447.5 kg/hm^2.适合长江流域、云贵高原及湖南地区早春设施和露地栽培.     

Opening the black box of food quality in the short supply chain: Effects of conventions of quality on consumer choice

In recent years new forms of food distribution organisation, known as short supply chains, have gained ground. The local nature of such distribution has positive effects on the environment and on the local economy. Consumers appear to trust the short supply chain, and it has achieved considerable success. However, the short supply chain has credence characteristics which, by their very nature, cannot be identified through a system of certification. The question we address in this paper is whether it is possible to identify the constituent elements of the credence trait in relation to food quality in the short supply chain. Our hypothesis is that the latter are linked to a range of socially constructed food quality criteria. To develop a more inclusive vision of how such criteria are coordinated in food quality assessment by consumers, use has been made of convention theory. In accordance with convention theory, quality is identified, in a social context and informally, as one of the spheres in which economic activity is regulated by procedures which go beyond regulation by price. The aim of our study was to measure the effects of coordinated conventions of quality in the context of one type of short supply chain: farmers’ markets specialised in the sale of organic products. An ordered logit model was implemented. Our results allow credence characteristics to be classified within conventions of quality and could help support strategies aimed at spreading sustainable forms of food distribution and consumption. Future research might go to the direction of validating our results based on a single form of supply organisation. Moreover, additional efforts should be made understanding the effect of situational factors on socio-demographic variables such as gender. Finally, an attempt should be made to merge different theories to better understand the issue of consumer choice.     

Young’s modulus evolution during heating,re-sintering and cooling of partially sintered alumina ceramics

The Young modulus of partially and fully sintered alumina ceramics, obtained by firing to different temperatures (range 1200–1600°C), has been determined via impulse excitation, and the evolution of Young’s modulus of partially sintered alumina with temperature has been monitored from room temperature to 1600°C. As expected, the room-temperature Young modulus of the partially sintered materials is lower than all theoretical predictions. With increasing temperature Young’s modulus decreases, until the original firing temperature is exceeded and sintering (densification) continues, resulting in a steep Young’s modulus increase. During heating and cooling the temperature dependence obeys a master curve for alumina, unless the temperature of the original firing is excessively low.     

Experimental determination of elastic modulus of elasticity and Poisson’s coefficient of date palm tree fiber

The present study is an attempt to valorize local vegetable fibers by evaluating thire effectiveness as a new composite biomaterial. Our aim was to determine the mechanical characteristics, namely the elastic modulus and Poisson’s coefficient, of a fiber, locally called “Lif,” that is a natural material extracted from different date palm tree varieties in Biskra, a region situated in southeastern Algeria. This study compares the mechanical characteristcs of the Lif date palm tree fiber with other synthetic and plant fibers studied previously.     

Drivers and enablers of supplier sustainability practices: a survey-based analysis

A rich research stream investigates the drivers and enablers of supplier sustainability practices, usually classified into suppliers’ monitoring and collaboration with suppliers. Differently from previous works analysing relationships between supplier sustainability practices and drivers or enablers, this research investigates how well-defined configurations of monitoring and collaboration can be characterised in terms of drivers and enablers. In this way, it intends to advance knowledge by identifying what drivers and enablers are important and distinctive for the different configurations of supplier sustainability practices. A first result is that moving from configurations of plants which less adopt supplier sustainability practices (i.e. non-adopters) to those which invest on monitoring and/or collaboration to a limited extent (i.e. partial adopters) up to the most advanced ones (i.e. full-adopters), the pressure due to cost reduction lessens its relative importance as a driver, while the pressure due to regulations remains essential. Other relevant results are that plant size acts as a barrier for non-adopters, and the alignment between the sustainability project and plant goals results determinant especially for full-adopters. This research also enriches the debate on the opportunity of differentiating between supplier monitoring and collaboration when investigating drivers/enablers, providing evidence of the risk of oversimplifications for some enablers/drivers.