Deciphering 3'ss selection in the yeast genome reveals an RNA thermosensor that mediates alternative splicing

Poor understanding of the spliceosomal mechanisms to select intronic 3' ends (3'ss) is a major obstacle to deciphering eukaryotic genomes. Here, we discern the rules for global 3'ss selection in yeast. We show that, in contrast to the uniformity of yeast splicing, the spliceosome uses all available 3'ss within a distance window from the intronic branch site (BS), and that in 70% of all possible 3'ss this is likely to be mediated by pre-mRNA structures. Our results reveal that one of these RNA folds acts as an RNA thermosensor, modulating alternative splicing in response to heat shock by controlling alternate 3'ss availability. Thus, our data point to a deeper role for the pre-mRNA in the control of its own fate, and to a simple mechanism for some alternative splicing.

African signatures of recent positive selection in human FOXI1

Background: The human FOXI1 gene codes for a transcription factor involved in the physiology of the inner ear, testis, and kidney. Using three interspecies comparisons, it has been suggested that this may be a gene underhuman-specific selection. We sought to confirm this finding by using an extended set of orthologous sequences.Additionally, we explored for signals of natural selection within humans by sequencing the gene in 20 Europeans,20 East Asians and 20 Yorubas and by analysing SNP variation in a 2 Mb region centered on FOXI1 in 39worldwide human populations from the HGDP-CEPH diversity panel.Results: The genome sequences recently available from other primate and non-primate species showed that FOXI1divergence patterns are compatible with neutral evolution. Sequence-based neutrality tests were not significant inEuropeans, East Asians or Yorubas. However, the Long Range Haplotype (LRH) test, as well as the iHS and XP-Rsbstatistics revealed significantly extended tracks of homozygosity around FOXI1 in Africa, suggesting a recentepisode of positive selection acting on this gene. A functionally relevant SNP, as well as several SNPs either on theputatively selected core haplotypes or with significant iHS or XP-Rsb values, displayed allele frequencies stronglycorrelated with the absolute geographical latitude of the populations sampled.Conclusions: We present evidence for recent positive selection in the FOXI1 gene region in Africa. Climate mightbe related to this recent adaptive event in humans. Of the multiple functions of FOXI1, its role in kidney-mediatedwater-electrolyte homeostasis is the most obvious candidate for explaining a climate-related adaptation.

Protocol of the COSMIN study: consensus-based standards for the selection of health measurement instruments

Background: Choosing an adequate measurement instrument depends on the proposed use of the instrument, the concept to be measured, the measurement properties (e.g. internal consistency, reproducibility, content and construct validity, responsiveness, and interpretability), the requirements, the burden for subjects, and costs of the available instruments. As far as measurement properties are concerned, there are no sufficiently specific standards for the evaluation of measurement properties of instruments to measure health status, and also no explicit criteria for what constitutes good measurement properties. In this paper we describe the protocol for the COSMIN study, the objective of which is to develop a checklist that contains COnsensus-based Standards for the selection of health Measurement INstruments, including explicit criteria for satisfying these standards. We will focus on evaluative health related patient-reported outcomes (HR-PROs), i.e. patient-reported health measurement instruments used in a longitudinal design as an outcome measure, excluding health care related PROs, such as satisfaction with care or adherence. The COSMIN standards will be made available in the form of an easily applicable checklist.Method: An international Delphi study will be performed to reach consensus on which and how measurement properties should be assessed, and on criteria for good measurement properties. Two sources of input will be used for the Delphi study: (1) a systematic review of properties, standards and criteria of measurement properties found in systematic reviews of measurement instruments, and (2) an additional literature search of methodological articles presenting a comprehensive checklist of standards and criteria. The Delphi study will consist of four (written) Delphi rounds, with approximately 30 expert panel members with different backgrounds in clinical medicine, biostatistics, psychology, and epidemiology. The final checklist will subsequently be field-tested by assessing the inter-rater reproducibility of the checklist.Discussion: Since the study will mainly be anonymous, problems that are commonly encountered in face-to-face group meetings, such as the dominance of certain persons in the communication process, will be avoided. By performing a Delphi study and involving many experts, the likelihood that the checklist will have sufficient credibility to be accepted and implemented will increase.

Interplay of spectral efficiency, power and doppler spectrum for reference-signal-assisted wireless communication

Expressions relating spectral efficiency, power, and Doppler spectrum, are derived for Rayleigh-faded wireless channels with Gaussian signal transmission. No side information on the state of the channel is assumed at the receiver. Rather, periodic reference signals are postulated in accordance with the functioning of most wireless systems. The analysis relies on a well-established lower bound, generally tight and asymptotically exact at low SNR. In contrast with most previous studies, which relied on block-fading channel models, a continuous-fading model is adopted. This embeds the Doppler spectrum directly in the derived expressions, imbuing them with practical significance. Closed-form relationships are obtained for the popular Clarke-Jakes spectrum and informative expansions, valid for arbitrary spectra, are found for the low- and high-power regimes. While the paper focuses on scalar channels, the extension to multiantenna settings is also discussed.

Edge detection by selection of pieces of level lines

We propose an edge detector based on the selection of wellcontrasted pieces of level lines, following the proposal ofDesolneux-Moisan-Morel (DMM) [1]. The DMM edge detectorhas the problem of over-representation, that is, everyedge is detected several times in slightly different positions.In this paper we propose two modifications of the originalDMM edge detector in order to solve this problem. The firstmodification is a post-processing of the output using a generalmethod to select the best representative of a bundle of curves.The second modification is the use of Canny’s edge detectorinstead of the norm of the gradient to build the statistics. Thetwo modifications are independent and can be applied separately.Elementary reasoning and some experiments showthat the best results are obtained when both modifications areapplied together.

Spectral efficiency in reference-signal-assisted low-power wireless communication

Expressions relating spectral efficiency, power and Doppler spectrum are derived for low-power Rayleighfaded wireless channels with proper complex signaling. Noside information on the state of the channel is assumed at the receiver. Rather, periodic reference signals are postulated inaccordance with the functioning of most wireless systems. In contrast with most previous studies, which relied on block-fading channel models, a continuous-fading model is adopted. This embeds the Doppler spectrum directly in thederived expressions thereby imbuing them with practical significance.

From a pattern-language to a pattern ontology approach for CSCL script design

Collaborative activities, in which students actively interact with each other, have proved to provide significant learning benefits. In Computer-Supported Collaborative Learning (CSCL), these collaborative activities are assisted by technologies. However, the use of computers does not guarantee collaboration, as free collaboration does not necessary lead to fruitful learning. Therefore, practitioners need to design CSCL scripts that structure the collaborative settings so that they promote learning. However, not all teachers have the technical and pedagogical background needed to design such scripts. With the aim of assisting teachers in designing effective CSCL scripts, we propose a model to support the selection of reusable good practices (formulated as patterns) so that they can be used as a starting point for their own designs. This model is based on a pattern ontology that computationally represents the knowledge captured on a pattern language for the design of CSCL scripts. A preliminary evaluation of the proposed approach is provided with two examples based on a set of meaningful interrelated patters computationally represented with the pattern ontology, and a paper prototyping experience carried out with two teaches. The results offer interesting insights towards the implementation of the pattern ontology in software tools.

The Point system of selection of immigrants in Quebec

The present paper is aimed at identifying what are the effects of the Point System of Selection of immigrants in Quebec. I defend that the distribution of points results in a different composition of immigrant stocks in terms of origin mix and not in terms of labour skills. To do so, I carry out a longitudinal descriptive analysis on the national composition of immigrants in Quebec and two other significant provinces (Ontario and British Columbia), as well as an analysis of the distribution of points in Quebec and in the rest of Canada.

Endogenous Credit Cycles and Financial Dampening in an Adverse Selection Economy

We propose an adverse selection framework in which the financial sector has a dual role. It amplifies or dampens exogenous shocks and also generates endogenous fluctuations. We fully characterize constrained optimal contracts in a setting in which entrepreneurs need to borrow and are privately informed about the quality of their projects. Our characterization is novel in analyzing pooling and separating allocations in a context of multi-dimensional screening: specifically, the amounts of investment undertaken and of entrepreneurial net worth are used to screen projects. We then embed these results in a dynamic competitive economy. First, we show how endogenous regime switches in financial contracts may generate fluctuations in an economy that exhibits no dynamics under full information. Unlike previous models of endogenous cycles, our result does not rely on entrepreneurial net worth being counter-cyclical or inconsequential for determining investment. Secondly, the model shows the different implications of adverse selection as opposed to pure moral hazard. In particular, and contrary to standard results in the macroeconomic literature, the financial system may dampen exogenous shocks in the presence of adverse selection.

Adverse Selection, Credit, and Efficiency: the Case of the Missing Market

We analyze a standard environment of adverse selection in credit markets. In our envi- ronment, entrepreneurs who are privately informed about the quality of their projects need to borrow from banks. As is generally the case in economies with adverse selection, the competitive equilibrium of our economy is shown to be ine¢ cient. Under adverse selection, the choices made by one type of agents limit what can be o¤ered to other types in an incentive-compatible manner. This gives rise to an externality, which cannot be internalized in a competitive equilibrium. We show that, in this type of environment, the ine¢ ciency associated to adverse selection is the consequence of one implicit assumption: entrepreneurs can only borrow from banks. If an additional market is added (say, a .security market.), in which entrepreneurs can obtain funds beyond those o¤ered by banks, we show that the e¢ cient allocation is an equilibrium of the economy. In such an equilibrium, all entrepreneurs borrow at a pooling rate in the security market. When they apply to bank loans, though, only entrepreneurs with good projects pledge these additional funds as collateral. This equilibrium thus simultaneously entails cross- subsidization and separation between di¤erent types of entrepreneurs.

Adverse selection, credit, and efficiency: the case of the missing market

We analyze a standard environment of adverse selection in credit markets. In our environment, entrepreneurs who are privately informed about the quality of their projects need to borrow in order to invest. Conventional wisdom says that, in this class of economies, the competitive equilibrium is typically inefficient. We show that this conventional wisdom rests on one implicit assumption: entrepreneurs can only access monitored lending. If a new set of markets is added to provide entrepreneurs with additional funds, efficiency can be attained in equilibrium. An important characteristic of these additional markets is that lending in them must be unmonitored, in the sense that it does not condition total borrowing or investment by entrepreneurs. This makes it possible to attain efficiency by pooling all entrepreneurs in the new markets while separating them in the markets for monitored loans.

Optimal Contracts, Adverse Selection, and Social Preferences: An Experiment

It has long been standard in agency theory to search for incentive-compatible mechanisms on the assumption that people care only about their own material wealth. However, this assumption is clearly refuted by numerous experiments, and we feel that it may be useful to consider nonpecuniary utility in mechanism design and contract theory. Accordingly, we devise an experiment to explore optimal contracts in an adverse-selection context. A principal proposes one of three contract menus, each of which offers a choice of two incentive-compatible contracts, to two agents whose types are unknown to the principal. The agents know the set of possible menus, and choose to either accept one of the two contracts offered in the proposed menu or to reject the menu altogether; a rejection by either agent leads to lower (and equal) reservation payoffs for all parties. While all three possible menus favor the principal, they do so to varying degrees. We observe numerous rejections of the more lopsided menus, and approach an equilibrium where one of the more equitable contract menus (which one depends on the reservation payoffs) is proposed and agents accept a contract, selecting actions according to their types. Behavior is largely consistent with all recent models of social preferences, strongly suggesting there is value in considering nonpecuniary utility in agency theory.

A Model of Collateral, Investment, and Adverse Selection

This paper characterizes the relationship between entrepreneurial wealth and aggregate investment under adverse selection. Its main finding is that such a relationship need not be monotonic. In particular, three results emerge from the analysis: (i) pooling equilibria, in which investment is independent of entrepreneurial wealth, are more likely to arise when entrepreneurial wealth is relatively low; (ii) separating equilibria, in which investment is increasing in entrepreneurial wealth, are most likely to arise when entrepreneurial wealth is relatively high and; (iii) for a given interest rate, an increase in entrepreneurial wealth may generate a discontinuous fall in investment.

Interviews and adverse selection

Interviewing in professional labor markets is a costly process for firms. Moreover, poor screening can have a persistent negative impact on firms bottom lines and candidates careers. In a simple dynamic model where firms can pay a cost to interview applicants who have private information about their own ability, potentially large inefficiencies arise from information-based unemployment, where able workers are rejected by firms because of their lack of offers in previous interviews. This effect may make the market less efficient than random matching. We show that the first best can be achieved using either a mechanism with transfers or one without transfers.