Relieving the first bottleneck in the drug discovery pipeline:using array technologies to rationalize membrane protein production

The slow down in the drug discovery pipeline is, in part, owing to a lack of structural and functional information available for new drug targets. Membrane proteins, the targets of well over 50% of marketed pharmaceuticals, present a particular challenge. As they are not naturally abundant, they must be produced recombinantly for the structural biology that is a prerequisite to structure-based drug design. Unfortunately, however, obtaining high yields of functional, recombinant membrane proteins remains a major bottleneck in contemporary bioscience. While repeated rounds of trial-and-error optimization have not (and cannot) reveal mechanistic details of the biology of recombinant protein production, examination of the host response has provided new insights. To this end, we published an early transcriptome analysis that identified genes implicated in high-yielding yeast cell factories, which has enabled the engineering of improved production strains. These advances offer hope that the bottleneck of membrane protein production can be relieved rationally.

Real options and demographic decisions:empirical evidence from East and West Germany

Iyer and Velu (2006) have convincingly argued that contemporary analyses of fertility behaviour fail to explain why a woman (or a couple) will choose to postpone childbirth, and in particular to consider the role of uncertainty in this regard. They have addressed this lacuna in the literature by using a real options approach to model fertility decisions by relating uncertainty experienced by individuals to the likelihood of childbirth. However, they did not present empirical evidence. Since the theory implies the existence of two offsetting effects of uncertainty on fertility decisions, a positive insurance effect and a negative option value effect, it is not easy to reject the theory on the basis of empirical analysis, when one of these effects offsets the other. We construct such a test for East (and also West) Germany during that country's reunification, which takes advantage of the fact that because of the country's strong welfare system, the insurance effect should be dominated by the option value effect, thereby suggesting that the net relationship should be negative. The results provide rather strong support for the real options link, especially for Eastern Germany.

Harnessing demographic differences in organizations:what moderates the effects of workplace diversity?

To account for the double-edged nature of demographic workplace diversity (i.e,. relational demography, work group diversity, and organizational diversity) effects on social integration, performance, and well-being related variables, research has moved away from simple main effect approaches and started examining variables that moderate these effects. While there is no shortage of primary studies of the conditions under which diversity leads to positive or negative outcomes, it remains unclear which contingency factors make it work. Using the Categorization-Elaboration Model as our theoretical lens, we review variables moderating the effects of workplace diversity on social integration, performance, and well-being outcomes, focusing on factors that organizations and managers have control over (i.e., strategy, unit design, human resource, leadership, climate/culture, and individual differences). We point out avenues for future research and conclude with practical implications.

We know what you want to buy:a demographic-based system for product recommendation on microblogs

Product recommender systems are often deployed by e-commerce websites to improve user experience and increase sales. However, recommendation is limited by the product information hosted in those e-commerce sites and is only triggered when users are performing e-commerce activities. In this paper, we develop a novel product recommender system called METIS, a MErchanT Intelligence recommender System, which detects users' purchase intents from their microblogs in near real-time and makes product recommendation based on matching the users' demographic information extracted from their public profiles with product demographics learned from microblogs and online reviews. METIS distinguishes itself from traditional product recommender systems in the following aspects: 1) METIS was developed based on a microblogging service platform. As such, it is not limited by the information available in any specific e-commerce website. In addition, METIS is able to track users' purchase intents in near real-time and make recommendations accordingly. 2) In METIS, product recommendation is framed as a learning to rank problem. Users' characteristics extracted from their public profiles in microblogs and products' demographics learned from both online product reviews and microblogs are fed into learning to rank algorithms for product recommendation. We have evaluated our system in a large dataset crawled from Sina Weibo. The experimental results have verified the feasibility and effectiveness of our system. We have also made a demo version of our system publicly available and have implemented a live system which allows registered users to receive recommendations in real time. © 2014 ACM.

Exploring demographic information in social media for product recommendation

In many e-commerce Web sites, product recommendation is essential to improve user experience and boost sales. Most existing product recommender systems rely on historical transaction records or Web-site-browsing history of consumers in order to accurately predict online users’ preferences for product recommendation. As such, they are constrained by limited information available on specific e-commerce Web sites. With the prolific use of social media platforms, it now becomes possible to extract product demographics from online product reviews and social networks built from microblogs. Moreover, users’ public profiles available on social media often reveal their demographic attributes such as age, gender, and education. In this paper, we propose to leverage the demographic information of both products and users extracted from social media for product recommendation. In specific, we frame recommendation as a learning to rank problem which takes as input the features derived from both product and user demographics. An ensemble method based on the gradient-boosting regression trees is extended to make it suitable for our recommendation task. We have conducted extensive experiments to obtain both quantitative and qualitative evaluation results. Moreover, we have also conducted a user study to gauge the performance of our proposed recommender system in a real-world deployment. All the results show that our system is more effective in generating recommendation results better matching users’ preferences than the competitive baselines.

Survival in the pre-senile dementia frontotemporal lobar degeneration with TDP-43 proteinopathy:effects of genetic, demographic and neuropathological variables

Factors associated with survival were studied in 84 neuropathologically documented cases of the pre-senile dementia frontotemporal dementia lobar degeneration (FTLD) with transactive response (TAR) DNA-binding protein of 43 kDa (TDP-43) proteinopathy (FTLD-TDP). Kaplan-Meier survival analysis estimated mean survival as 7.9 years (range: 1-19 years, SD = 4.64). Familial and sporadic cases exhibited similar survival, including progranulin (GRN) gene mutation cases. No significant differences in survival were associated with sex, disease onset, Braak disease stage, or disease subtype, but higher survival was associated with lower post-mortem brain weight. Survival was significantly reduced in cases with associated motor neuron disease (FTLD-MND) but increased with Alzheimer's disease (AD) or hippocampal sclerosis (HS) co-morbidity. Cox regression analysis suggested that reduced survival was associated with increased densities of neuronal cytoplasmic inclusions (NCI) while increased survival was associated with greater densities of enlarged neurons (EN) in the frontal and temporal lobes. The data suggest that: (1) survival in FTLD-TDP is more prolonged than typical in pre-senile dementia but shorter than some clinical subtypes such as the semantic variant of primary progressive aphasia (svPPA), (2) MND co-morbidity predicts poor survival, and (3) NCI may develop early and EN later in the disease. The data have implications for both neuropathological characterization and subtyping of FTLD-TDP.