Informational efficiency and welfare

In a continuous-time market with a safe rate and a risky asset that pays a dividend stream depending on a latent state of the economy, several agents make consumption and investment decisions based on public information–prices and dividends–and private signals. If each investor has constant absolute risk aversion, equilibrium prices do not reveal all the private signals, but lead to the same estimate of the state of the economy that one would hypothetically obtain from the knowledge of all private signals. Accurate information leads to low volatility, ostensibly improving market efficiency, but also reduces each agent’s consumption through a decrease in the price of risk. Thus, informational efficiency is reached at the expense of agents’ welfare

A structural study of copper(II) carboxylates: Crystal structure and physical characterisation of [Cu2(2-bromopropanoato)4(caffeine)2]

Based on the bond-valence sum model the continual transition between the bidentate and monodentate bonding mode of carboxylato group and minimum of Cu-O bond lengths were estimated. The dependence of Cu⋯Cu separation on Cu-N bond length in binuclear Cu(II) carboxylates with caffeine were derived and fitted to the observed data. The crystal structure of [Cu2(2-bromopropanoato)4(caffeine)2] has been determined by X-ray crystallography. The structure consists of centrosymmetric binuclear units where the two Cu atoms are coordinated by four disordered bridging 2-bromopropionates and two caffeine ligands at the apices of a bicapped square prism. Both 2-bromopropionates show disorder of their -Br and -CH3 substituents. Stacking π·π interactions between the adjacent caffeine molecules link the complex units in 1-D networks. The binuclear structure of the studied compound is consistent with magnetic data and EPR spectru

Radial Distribution of Distant Trans-Neptunian Objects Points to Sun's Formation in a Stellar Cluster

The Scattered Disk Objects (SDOs) are a population of trans-Neptunian bodies with semimajor axes $50< a \lesssim 1000$ au and perihelion distances $q \gtrsim 30$ au. The detached SDOs with orbits beyond the reach of Neptune (roughly $q>35$~au) are of special interest here as an important constraint on the early evolution of the outer Solar System. The semimajor axis profile of detached SDOs at 50--500~au, as characterized from the Dark Energy Survey (DES), is radially extended, but previous dynamical models of Neptune's early migration produce a relatively compact profile. This problem is most likely related to Sun's birth environment in a stellar cluster. We perform new dynamical simulations that account for cluster effects and show that the orbital distribution of SDOs can be explained if a particularly close stellar encounter occurred early on (e.g., M dwarf with the mass $\simeq 0.2$ $M_\odot$ approaching the Sun at $\simeq 200$ au). For such an encounter to happen with a reasonably high probability the Sun must have formed in a stellar cluster with $\eta T \gtrsim 10^4$ Myr pc$^{-3}$, where $\eta$ is the stellar number density and $T$ is the Sun's residence time in the cluster

Multi-academy Trusts: do they make a difference to pupil outcomes?

This report is published as a supplement to the main project research report, Hierarchy, Markets and Networks: Analysing the ‘self-improving school-led system’ agenda in England and the implications for schools. The main project report analyses how schools in England have interpreted and begun to respond to the government’s ‘self-improving school-led system’ (SISS) policy agenda, an overarching narrative for schools policy since 2010 that encompasses an ensemble of reforms including academies, multi-academy trusts (MATs) and teaching school alliances (TSAs). The statistical analysis of MAT impact on pupil attainment and progress set out in this supplementary report is the first published analysis to compare schools in MATs over a three-year period with standalone academies and maintained schools with similar characteristics and levels of prior pupil attainment. The analysis set out here uses 2013–15 attainment data and 2016 data on the composition of MATs. Our finding in this paper that there is no positive impact from MAT status overall is largely consistent with other recent studies (Hutchings and Francis, 2017; Andrews, 2019). Where this report provides significant new evidence is in terms of MAT size, as we show that pupils in small and mid-sized MATs tend to perform better, on average, than their peers in comparable maintained schools in both phases and, in the primary phase, than comparable standalone academies. Conversely, secondary school pupils in larger MATs (with 16+ schools) tend to do worse compared to those in both standalone academies and maintained schools. These findings suggest that the economic drive for MAT growth promoted in contemporary policy may well be in tension with an educational argument for smaller groupings of schools

Proposta de utilização de embalagem Flexitank na indústria de suplemento animal

Orientador : Prof. Dr. Roberto CerviMonografia (especialização) - Universidade Federal do Paraná, Curso de MBA em Gerencia de Sistemas Logísticos.Inclui referênciasResumo : O presente artigo visa descrever a viabilidade na implementação da embalagem flexitank, num estudo de caso à realizar-se em uma empresa situada em Biguaçu – SC. Seu segmento refere-se à produção de suplemento animal com venda no mercado interno e exportação de seus produtos. Atualmente, as exportações são realizadas através do envase de seus produtos utilizando embalagens do tipo IBC em seus embarques internacionais. O estudo propõe a alteração da embalagem atual por embalagens do tipo flexitank, visando mais eficiência no processo e redução de custos em todo o fluxo operacional. No decorrer do artigo, define-se o conceito de embalagem, sua importância e principais funções e aplicações na indústria e na logística. Descreve-se também, os custos operacionais que podem ocorrer em todo o fluxo de carregamento e sugere a capacitação e treinamento de pessoal adequado para acompanhamento de todos os embarques. A metodologia empregada nesta pesquisa foi do tipo quantitativo, exploratório, documental, sendo um estudo de caso. Com a análise dos dados obtidos, através de pesquisa realizada na organização, demonstrou-se que a mudança, do tipo de embalagem utilizada na empresa no processo de embarque, seria efetiva e acertada, pois diminuiria os custos operacionais e de tempo de trabalho, aumentando a eficiência da organização

Functional and molecular characterization of pendrin, the anion exchanger involved in Pendred syndrome, non-syndromic deafness and respiratory distresses.

Pendrin is an anion exchanger with affinity for several monovalent anions including iodide, chloride and bicarbonate. It is expressed in the inner ear, thyroid and kidney and more recently was also detected in the airways and in a number of other tissues. Pendrin was first identified as the protein that, if mutated, is responsible for the pathology referred to as Pendred syndrome, an autosomal recessive disorder characterized by bilateral sensorineural hearing loss associated to thyroid dysfunction with or without involvement of the vestibular system. Hypo- or non-functional mutations of pendrin are also responsible for the development of unilateral or bilateral hearing loss with enlargement of the vestibular aqueduct with no involvement of other organs (non-syndromic EVA). On the other hand, also the overexpression and hyper-function of pendrin have recently been associated with a number of other pathologies, such as hypertension, asthma and chronic obstructive pulmonary disease (COPD). In this work, we performed the functional characterization of 7 pendrin variants identified in a cohort of 58 deaf patients by our collaborators of the University of Campinas (Sao Paolo, Brazil), in order to define their role in the observed phenotype. The analysis of pendrin activity was performed by means of a fluorometric assay based on a halide-sensitive enhanced yellow fluorescence protein (EYFP) variant. Furthermore, the molecular defect of such mutants was analyzed, defining their subcellular localization and expression levels by means of confocal microscopy and western blot. We could assess the degree of functional impairment of the analyzed pendrin variants, contributing therefore to the genetic diagnosis of the screened patients. The genetic diagnosis of 5 out of 14 patients was definitively assessed as pendrin-related deafness, while for the remaining patients further genetic investigation is necessary, involving pendrin promoter and 3\u2019-UTR, as well as further deafness related genes. We could observe a clear correlation between measured functional impairment, sub-cellular localization and expression levels of these specific variants. In particular, loss of function variants (T193I and L445W) are retained in the ER and completely excluded from the plasma membrane, while reduction of function mutations (P142L, G149R, C282Y) show at least a partial trafficking to the PM. Based on these findings we hypothesized that pendrin mutant isoforms are targeted for proteasomal degradation. Starting from this hypothesis we could show that pharmacological inhibition of proteasomal degradation with 10\ub5M MG132 was capable to recover (i) total and (ii) plasma membrane expression levels of pendrin variants and, most importantly, (iii) transport activity of specific pendrin variants (P142L, T183I, Q413R, L445W) was improved upon treatment. Such result allows for further development of possible rescuing approaches of pendrin transport activity as a potential treatment of pendrin-related pathologies. A second part of the present study focuses on the search of a specific ligand of pendrin, with the aim of modulating the activity of the transporter, especially in those cases of pathological over-expression and hyperactivity, such as asthma, COPD and hypertension. No specific, non-toxic and potent inhibitor of pendrin could be identified so far and the screening of large compound libraries failed in identifying potential inhibitors. We therefore adopted a more targeted selection of candidates for the screening. We selected compounds among (i) established anion exchangers inhibitors, (ii) inhibitors of the pendrin homologue DRA, (iii) common diuretics and antihypertensive agents, and (iv) via two bioinformatic tools: meta-analysis and SHED alignments. Meta-analysis is an approach aimed to the mathematical definition of a protein topology based on its primary aminoacidic sequence, with no knowledge of its three-dimensional structure. SHED profile allows for the mathematical definition of small compounds according to the intra-molecular distribution of specific atomic features. The effect of the candidates ligands on pendrin activity was evaluated by means of the same fluorometric assay mentioned earlier. In the present study we could (i) confirm the inhibitory effect of previously assessed active compounds, Niflumic acid and NPPB, (ii) define for the first time the inhibitory effect of the anti-inflammatory, anti-rheumatic drug tenidap. In a second screening phase on further compounds suggested by the alignment of the so far identified active compounds niflumic acid and tenidap, according to the SHED profilng, we were able to identify two further active compounds, N-(2-chlorophenyl)-2-(2,4-dibromophenoxy)acetamide and flufenamic acid

Single-stranded DNA : methods and application in nanotechnology

Basic molecular and cell research, production of recombinant proteins, diagnostic detection of genetic mutations, construction of nanostructures and high-throughput DNA sequencing are only a few examples of the diverse set of applications that are amenable thanks to the availability of synthetic DNA polymers in biomedicine. Strategic investments and technical progress together with the introduction of automation in the synthesis of DNA oligomers enabled to transform, in just a few decades, a process mastered only by a niche of biochemists into an affordable and available custom-made product to every scientific field. Despite such progress, innovation soon reached a plateau due to intrinsic limitations of the synthesis process, putting a barrier at two hundred nucleotides as the maximum length of synthetic DNA molecules. In the meanwhile, molecular biologists closed the gap thanks to a better understanding of polymerases and the mastering of directed evolution protocols making it possible to redesign processes that are more similar to what happens in nature, taking advantage of existing and improved enzymes for the generation of long and high-quality DNA molecules. This enabled to find novel applications for DNA such as gene editing or information storage. In this thesis I focused on the enzymatic production and functionalization of single stranded DNA. More specifically, in paper I we directed our attention to optimize the protocol for the templated enzymatic synthesis of oligonucleotides. We highlighted possible limitations of the technique and proposed a solution in employing a single stranded binding protein greatly decreasing double stranded DNA contaminants. In paper II we further extended the workflow. In here, we focused on continuing the previous protocol to accommodate the production of chimeric DNA-protein molecular tools needed in nanotechnology where DNA is considered more a building material rather than an information rich polymer while the actuation of a particular function is operated by proteins. We worked on a minimal bacteria-derived self-tagging domain that has the capacity to establish a covalent bond with a specific DNA sequence and some applications are suggested. Paper III represents the natural extension of this work even if, in this specific case, the earlier presented rational is reverted. More specifically, a biosensor for the detection of aquatic microorganisms was produced with the characterized bioconjugation technique where the chimeric protein was used as recognition moiety and the oligonucleotide as signal amplification device through its intrinsic DNAzyme activity. Finally, in Paper IV, we decided to use all the previously gathered knowledge – enzymatic DNA production and bioconjugation techniques – to conceive a novel basic biology investigation tool for the study of spatial organization of proteins. Here we took advantage of the possibility to grow a localized and unique DNA polymer with the ability to target proteins with DNA-protein chimeras. The resulting product is then recovered and decoded by next generation sequencing

A Bayesian approach to Mendelian randomization with multiple pleiotropic variants.

We propose a Bayesian approach to Mendelian randomization (MR), where instruments are allowed to exert pleiotropic (i.e. not mediated by the exposure) effects on the outcome. By having these effects represented in the model by unknown parameters, and by imposing a shrinkage prior distribution that assumes an unspecified subset of the effects to be zero, we obtain a proper posterior distribution for the causal effect of interest. This posterior can be sampled via Markov chain Monte Carlo methods of inference to obtain point and interval estimates. The model priors require a minimal input from the user. We explore the performance of our method by means of a simulation experiment. Our results show that the method is reasonably robust to the presence of directional pleiotropy and moderate correlation between the instruments. One section of the article elaborates the model to deal with two exposures, and illustrates the possibility of using MR to estimate direct and indirect effects in this situation. A main objective of the article is to create a basis for developments in MR that exploit the potential offered by a Bayesian approach to the problem, in relation with the possibility of incorporating external information in the prior, handling multiple sources of uncertainty, and flexibly elaborating the basic model

Dynamic information aggregation in asset prices

This thesis investigates how the information dispersed among market participants dynamically aggregates in asset prices, the extent to which prices reflect available information, and how such information affects investors’ decisions. The main model considers a population of investors with different absolute risk aversions and time-varying, diverse signals on the growth rate of an asset’s dividends. Each investor bids the asset based on the information in his private signal and in the asset price itself, which is determined in equilibrium by the market-clearing condition and partially reflects the signals of other market participants. The dividend stream is driven by a latent variable, which investors strive to estimate based on their individual, private information, and on the common knowledge revealed by prices. We find in closed form equilibrium prices and the optimal behaviour of the agents. Price volatility depends on the volatility of dividends and on the volatility of the estimate of the latent variable, which is revealed to all agents through prices. Equilibrium prices do not reveal all the private signals of market participants, but the same estimate of the state of the economy that an agent with all private signals would be able to obtain. Put differently, prices reveal not all information but all relevant information. The first chapter presents a baseline model, where the only noise in the market is on the stochastic dividend process. In the second chapter dividends become mean reverting to a state variable observed by all agents - the state of the economy - which fluctuates over time. The state of the economy is unobservable in the last chapter, but market participants have individual information, which jointly with asset prices, helps them to estimate the latent variable