Peppered Moth

A prose stor

Letter from Editor

This is the introductory letter from Assistant Editor Connie Shen

Yellow, the Color

A poe

Jiejie

A prose stor

Determining the Optimal Fee-Technical Proposal Combination in Two Envelope Fee Bidding

Two envelope fee bidding is a mechanism used by construction clients to allocate commissionsto willing consultants such as architects, engineers and surveyors. In two envelopefee bidding the client scores the competing consultants’ fees and technical proposals.The fee and technical proposal scores are weighted and aggregated and the consultantobtaining the highest aggregated score normally wins the commission. The consultant’sobjective in bidding, therefore, is to obtain the highest aggregated score possible since thismaximizes the chance of winning the commission. Given that fee and technical proposalscores are to some extent correlated, consultants can submit any one from a number ofdifferent fee—technical proposal combinations, ranging from a low fee—low scored technicalproposal combination to a high fee—high scored technical proposal combination.Only one possible combination will result in the highest aggregated score. Drew et al(2002b) offered consultants a model to determine this optimum fee-technical proposalcombination for any given commission. This paper tests the proposed model using datacollected from a leading Hong Kong consultant. The analysis, based on 51 bidding attempts,indicates that had the consultant adopted the proposed optimization model, theoverall average improvement on the consultant’s original total scores was 7.07%. The optimumstrategy was to aim for an absolute low fee—low scored technical proposal on 20occasions, absolute high scored technical proposal—high fee on 21 occasions and somewherebetween these two extremes on the remaining 10 occasions. The extent to whichfees scores and technical scores vary relative to each other has an important influence onthe optimum fee—technical proposal combination. However, the client’s change from a70/30 to a 50/50 predetermined weighting appears to have little effect on the consultant’soptimum bidding strategy

Factors that Modify and Control Bcl11b, a Tumor Suppressor Protein

The experiments explained in this Honors thesis are focused on finding a cellular model for analyzing Bcl11b, a transcription factor dysregulated in 20% of cases of T-cell Acute Lymphoblastic Leukemia (T-ALL). Acute Lymphoblastic Leukemia is the most common childhood cancer. Because T-ALL is a result of incorrect thymocyte development, research into how T-cells mature is essential. A key factor in T-cell maturation is the transcription factor Bcl11b. Two key Bcl11b post-translational modifications include phosphorylation and sumoylation, of which Bcl11b has 23 and 2 sites, respectively. The first experiments attempted to identify an ideal model for studying Bcl11b; however both cellular models tested had negative characteristics. Mouse thymocytes could not be transfected using the Invitrogen Neon® Electroporation System. P2C2 cells post-translationally modified Bcl11b differently than thymocytes. The next experiment was to identify which of Bcl11b’s phosphorylation sites contribute more towards the composite phosphorylation level and was more important in cell signaling. This was done with Bcl11b mutants that had key phosphorylation sites eliminated. While initial data suggested that mutating phosphorylation sites affected overall phosphorylation levels, subsequent experiments resulted in conflicting data suggesting that the number of phosphorylation sites eliminated had little effect on the expressed composite phosphorylation level of Bcl11b

Characterizing User Behavior and Information Propagation on a Social Multimedia Network

An increasing portion of modern socializing takes place via online social networks. Members of these communities often play distinct roles that can be deduced from observations of users' online activities. One such activity is the sharing of multimedia, the popularity of which can vary dramatically. Here we discuss our initial analysis of anonymized, scraped data from consenting Facebook users, together with associated demographic and psychological profiles. We present five clusters of users with common observed online behaviors, where these users also show correlated profile characteristics. Finally, we identify some common properties of the most popular multimedia content.Comment: 6 pages, 5 figures, 2 tables, to be published in the proceedings of the Int. Workshop on Social Multimedia Research (SMMR) 2013. 2013 IEE

Massively parallel cis-regulatory analysis in the mammalian central nervous system

Cis-regulatory elements (CREs, e.g., promoters and enhancers) regulate gene expression, and variants within CREs can modulate disease risk. Next-generation sequencing has enabled the rapid generation of genomic data that predict the locations of CREs, but a bottleneck lies in functionally interpreting these data. To address this issue, massively parallel reporter assays (MPRAs) have emerged, in which barcoded reporter libraries are introduced into cells, and the resulting barcoded transcripts are quantified by next-generation sequencing. Thus far, MPRAs have been largely restricted to assaying short CREs in a limited repertoire of cultured cell types. Here, we present two advances that extend the biological relevance and applicability of MPRAs. First, we adapt exome capture technology to instead capture candidate CREs, thereby tiling across the targeted regions and markedly increasing the length of CREs that can be readily assayed. Second, we package the library into adeno-associated virus (AAV), thereby allowing delivery to target organs in vivo. As a proof of concept, we introduce a capture library of about 46,000 constructs, corresponding to roughly 3500 DNase I hypersensitive (DHS) sites, into the mouse retina by ex vivo plasmid electroporation and into the mouse cerebral cortex by in vivo AAV injection. We demonstrate tissue-specific cis-regulatory activity of DHSs and provide examples of high-resolution truncation mutation analysis for multiplex parsing of CREs. Our approach should enable massively parallel functional analysis of a wide range of CREs in any organ or species that can be infected by AAV, such as nonhuman primates and human stem cell-derived organoids