Thinking small: zinc-sensing by the gut epithelium.

pre-print341 K

Yrityksen Tekes-rahoitteisen projektin tilintarkastus

Innovaatiorahoituskeskus Tekes rahoitti vuonna 2016 suomalaisten yritysten toteuttamia projekteja noin 467 miljoonalla eurolla. Useimpien Tekesin tarjoamien rahoituspalvelujen ehtona on rahoituksen tilityksen tarkistuttaminen auktorisoidulla tilintarkastajalla. Työn tavoitteena on tuottaa Tekes-rahoitteisten projektien tarkastusta varten osin tarkastusta ohjaava dokumentaatiopohja, tarjota opinnäytetyön raporttiosalla dokumentaatiopohjaa tukeva katsaus Tekes-rahoitteisten projektien tarkastukseen ja syventää kirjoittajan vielä kapeaa osaamista projektitarkastuksista. Opinnäytetyössä keskitytään Tekesin yrityksille tarjoamien rahoitusmuotojen tarkastuksen erityispiirteisiin eikä raporttia tai dokumentaatiopohjaa voida soveltaa julkisten toimijoiden projektien tarkastuksiin. Työ toteutettiin laatien teoriapohja tilintarkastuksen tavoitteista ja eri toimeksiannoista, julkisen rahoituksen ja Tekesin rooleista rahoittajana sekä niistä normeista ja sääntelyistä, jotka koskevat julkisen rahoituksen tilitysten tarkastusta. Teoriapohjan lisäksi tuotettiin luku Tekes-rahoitteisen projektin tarkastuksen teknisestä toteutuksesta osin Tekesin vuoden 2017 yleisten rahoitusehtojen ja tarkastusraporttipohjien sekä auktorisoidun tilintarkastajan ja Tekesin maksatuspalvelujohtajan haastattelujen pohjalta. Tämän osion rinnalla tuotettiin Tekes-rahoitteisten projektien tarkastuksia varten dokumentaatiopohja, joka koottiin kokonaisuudeksi raportin liitteisiin. Tekesin maksatuspalvelujohtaja Anne Kleemolan haastattelun tuloksena todettiin, etteivät Tekesin nykyiset tarkastusraporttipohjat huomioi erityisehtojen tarkastusta yhtä yksityiskohtaisesti, kuin tarkastusraporttipohjalla olevat muut tarkastuksessa huomioitavat seikat on huomioitu. Kleemola totesi tämän olevan hyödyllinen huomio ja tarkastusraporttipohjiin mahdollisesti kehitettävä asia. Koska toimeksiantajalle tuotetusta dokumentaatiopohjasta syntyi selkeä runko Tekes-rahoitteisen projektin tarkastukselle, projektitarkastuksien osalta koettiin oman osaamisen syventyneen ja yhteydenotto Tekesiin koettiin myös heidän osaltaan hyödylliseksi, opinnäytetyön voidaan todeta täyttäneen tavoitteensa

Treatment as Prevention: Should Hepatitis C Learn the Lessons from HIV?

Long-term experience in the treatment of HIV-infected individuals has shown indirect benefits of early initiation of antiretroviral therapy, particularly in preventing HIV transmission. With the advent of direct-acting antivirals for the treatment of hepatitis C, the strategy of treatment-as-prevention has become feasible. However, economic, clinical, ethical, and public health issues arise from the concept of using therapeutic interventions only as prevention strategies

The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis

Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P = 1.34×10<sup>−8</sup>, OR = 1.22, CI 95% = 1.14–1.30; rs2004640: P = 4.60×10<sup>−7</sup>, OR = 0.84, CI 95% = 0.78–0.90; rs10488631: P = 7.53×10<sup>−20</sup>, OR = 1.63, CI 95% = 1.47–1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P = 9.04×10<sup>−22</sup>, OR = 1.75, CI 95% = 1.56–1.97) better explained the observed association (likelihood P-value = 1.48×10<sup>−4</sup>), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that this association is not sub-phenotype-specific

Abnormal Vestibular Evoked Myogenic Potentials in Medial Medullary Infarction

Background The medial vestibulospinal tract (MVST), which descends in the medial longitudinal fasciculus (MLF), may mediate the vestibular evoked myogenic potentials (VEMPs) in the contracting sternocleidomastoid muscle. We report herein abnormal VEMPs in a patient with medial medullary infarction (MMI) that appeared to involve the MLF. Case Report A patient with infarction involving the right medial medulla showed decreased p13-n23 amplitude and increased p13/n23 latencies of the VEMPs on the right side. These abnormal VEMPs recorded in all MMI patient support the theory that VEMPs are mediated by the MVST contained within the MLF. Conclusions VEMPs may represent a valuable tool for investigating vestibular dysfunction originating from the saccule, even ill patients with central vestibulopathies, which is not readily defined by conventional vestibular function tests. J Clin Neurol 2009;5:101-103This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A080750). The authors thank Jong-Hee Lee for experimental assistance.Kim JS, 2005, NEUROLOGY, V65, P1294Welgampola MS, 2005, NEUROLOGY, V64, P1682Newlands SD, 2003, J COMP NEUROL, V466, P31, DOI 10.1002/cne.10876Chen CH, 2003, LARYNGOSCOPE, V113, P990Murofushi T, 1999, ARCH OTOLARYNGOL, V125, P660Murofushi T, 1996, ARCH OTOLARYNGOL, V122, P845WILSON VJ, 1995, J VESTIBUL RES-EQUIL, V5, P147MUROFUSHI T, 1995, EXP BRAIN RES, V103, P174ROBERTSON DD, 1995, J OTOLARYNGOL, V24, P3COLEBATCH JG, 1994, J NEUROL NEUROSUR PS, V57, P190COLEBATCH JG, 1992, NEUROLOGY, V42, P1635AKAIKE T, 1983, BRAIN RES, V259, P217FERNANDEZ C, 1976, J NEUROPHYSIOL, V39, P970POMPEIANO O, 1957, ARCH ITAL BIOL, V95, P166

Reasoning deficits among illicit drug users are associated with aspects of cannabis use

Background. Deficits in deductive reasoning have been observed among ecstasy/polydrug users. The present study seeks to investigate dose-related effects of specific drugs and whether these vary with the cognitive demands of the task. Methods. One hundred and five participants (mean age 21.33, S.D. 3.14; 77 females, 28 males) attempted to generate solutions for eight one-model syllogisms and one syllogism for which there was no valid conclusion (NVC). All of the one model syllogisms generated at least one valid conclusion and six generated two valid conclusions. In these six cases one of the conclusions was classified as common and the other as non-common. Results. The number of valid common inferences was negatively associated with aspects of short term cannabis use and with measures of IQ. The outcomes observed were more than simple post intoxication effects since cannabis use in the 10 days immediately before testing was unrelated to reasoning performance. Following adjustment for multiple comparisons, the number of non-common valid inferences was not significantly associated with any of the drug use measures. Conclusions. Recent cannabis use appears to impair the processes associated with generating valid common inferences while not affecting the production of non-common inferences. It is possible, therefore, that the two types of inference may recruit different executive resources which may differ in their susceptibility to cannabis-related effects

Pleiotropic functions of the tumor- and metastasis-suppressing Matrix Metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice

Matrix metalloproteinase-8 (MMP-8; neutrophil collagenase) is an important regulator of innate immunity which has onco-suppressive actions in numerous tumor types

A Small Conductance Calcium-Activated K⁺ Channel in C. elegans, KCNL-2, Plays a Role in the Regulation of the Rate of Egg-Laying

In the nervous system of mice, small conductance calcium-activated potassium (SK) channels function to regulate neuronal excitability through the generation of a component of the medium afterhyperpolarization that follows action potentials. In humans, irregular action potential firing frequency underlies diseases such as ataxia, epilepsy, schizophrenia and Parkinson's disease. Due to the complexity of studying protein function in the mammalian nervous system, we sought to characterize an SK channel homologue, KCNL-2, in C. elegans, a genetically tractable system in which the lineage of individual neurons was mapped from their early developmental stages. Sequence analysis of the KCNL-2 protein reveals that the six transmembrane domains, the potassium-selective pore and the calmodulin binding domain are highly conserved with the mammalian homologues. We used widefield and confocal fluorescent imaging to show that a fusion construct of KCNL-2 with GFP in transgenic lines is expressed in the nervous system of C. elegans. We also show that a KCNL-2 null strain, kcnl-2(tm1885), demonstrates a mild egg-laying defective phenotype, a phenotype that is rescued in a KCNL-2-dependent manner. Conversely, we show that transgenic lines that overexpress KCNL-2 demonstrate a hyperactive egg-laying phenotype. In this study, we show that the vulva of transgenic hermaphrodites is highly innervated by neuronal processes and by the VC4 and VC5 neurons that express GFP-tagged KCNL-2. We propose that KCNL-2 functions in the nervous system of C. elegans to regulate the rate of egg-laying. © 2013 Chotoo et al

Portfolio selection problems in practice: a comparison between linear and quadratic optimization models

Several portfolio selection models take into account practical limitations on the number of assets to include and on their weights in the portfolio. We present here a study of the Limited Asset Markowitz (LAM), of the Limited Asset Mean Absolute Deviation (LAMAD) and of the Limited Asset Conditional Value-at-Risk (LACVaR) models, where the assets are limited with the introduction of quantity and cardinality constraints. We propose a completely new approach for solving the LAM model, based on reformulation as a Standard Quadratic Program and on some recent theoretical results. With this approach we obtain optimal solutions both for some well-known financial data sets used by several other authors, and for some unsolved large size portfolio problems. We also test our method on five new data sets involving real-world capital market indices from major stock markets. Our computational experience shows that, rather unexpectedly, it is easier to solve the quadratic LAM model with our algorithm, than to solve the linear LACVaR and LAMAD models with CPLEX, one of the best commercial codes for mixed integer linear programming (MILP) problems. Finally, on the new data sets we have also compared, using out-of-sample analysis, the performance of the portfolios obtained by the Limited Asset models with the performance provided by the unconstrained models and with that of the official capital market indices