Pob1 participates in the Cdc42 regulation of fission yeast actin cytoskeleton.

Rho GTPases regulate the actin cytoskeleton in all eukaryotes. Fission yeast Cdc42 is involved in actin cable assembly and formin For3 regulation. We isolated cdc42-879 as a thermosensitive strain with actin cable and For3 localization defects. In a multicopy suppressor screening, we identified pob1(+) as suppressor of cdc42-879 thermosensitivity. Pob1 overexpression also partially restores actin cables and localization of For3 in the mutant strain. Pob1 interacts with Cdc42 and this GTPase regulates Pob1 localization and/or stability. The C-terminal pleckstrin homology (PH) domain of Pob1 is required for Cdc42 binding. Pob1 also binds to For3 through its N-terminal sterile alpha motif (SAM) domain and contributes to the formin localization at the cell tips. The previously described pob1-664 mutant strain (Mol. Biol. Cell. 10, 2745-2757, 1999), which carries a mutation in the PH domain, as well as pob1 mutant strains in which Pob1 lacks the N-terminal region (pob1DeltaN) or the SAM domain (pob1DeltaSAM), have cytoskeletal defects similar to that of cdc42-879 cells. Expression of constitutively active For3DAD* partially restores actin organization in cdc42-879, pob1-664, pob1DeltaN, and pob1DeltaSAM. Therefore, we propose that Pob1 is required for For3 localization to the tips and facilitates Cdc42-mediated relief of For3 autoinhibition to stimulate actin cable formation.

ORMDL proteins are a conserved new family of endoplasmic reticulum membrane proteins

Background: Annotations of completely sequenced genomes reveal that nearly half of the genes identified are of unknown function, and that some belong to uncharacterized gene families. To help resolve such issues, information can be obtained from the comparative analysis of homologous genes in model organisms. Results: While characterizing genes from the retinitis pigmentosa locus RP26 at 2q31-q33, we have identified a new gene, ORMDL1, that belongs to a novel gene family comprising three genes in humans (ORMDL1, ORMDL2 and ORMDL3), and homologs in yeast, microsporidia, plants, Drosophila, urochordates and vertebrates. The human genes are expressed ubiquitously in adult and fetal tissues. The Drosophila ORMDL homolog is also expressed throughout embryonic and larval stages, particularly in ectodermally derived tissues. The ORMDL genes encode transmembrane proteins anchored in the endoplasmic reticulum (ER). Double knockout of the two Saccharomyces cerevisiae homologs leads to decreased growth rate and greater sensitivity to tunicamycin and dithiothreitol. Yeast mutants can be rescued by human ORMDL homologs. Conclusions: From protein sequence comparisons we have defined a novel gene family, not previously recognized because of the absence of a characterized functional signature. The sequence conservation of this family from yeast to vertebrates, the maintenance of duplicate copies in different lineages, the ubiquitous pattern of expression in human and Drosophila, the partial functional redundancy of the yeast homologs and phenotypic rescue by the human homologs, strongly support functional conservation. Subcellular localization and the response of yeast mutants to specific agents point to the involvement of ORMDL in protein folding in the ER.

Yrityksen jakelutoimintojen kehittäminen

Diplomityön tavoitteena oli turkiseläinrehun valmistajan, E - P:n Minkinrehu Oy:n, jakelutoimintojen nykytilan analysointi, kehityskohteiden etsiminen ja kehitystoimenpiteiden luominen. Logististen toimintojen nykytilaa pyrittiin selvittämään haastattelujen, tutustumiskäyntien sekä kerätyn aineiston avulla. Mukaan tarkasteluun otettiin myös alan kirjallisuutta. Tutkimuksen perusteella yrityksen suurimmat jakeluongelmat liittyivät puutteelliseen jakelun ja kuljetusten suunnitteluun, penis- ja lisäarvopalveluiden puuttumiseen sekä epämääräiseen jakeluhinnoittelumenetelmään. Osa ongelmista aiheutui toimialan ominaispiirteistä, kuten sesonkiluontoisuudesta, erikoisjakelukaluston käytöstä, kalliista varastointimenetelmistä ja tuotteiden pilaantumisherkkyydestä. Jakeluun liittyviä ongelmia olivat jakelun kohdistamisongelma ja paluukuormien puuttuminen. Edellä mainituista ominaispiirteistä ja ongelmista johtuen jakelu- ja kuljetuskustannukset olivat noin 4,5 miljoonaa euroa eli lähes 20 prosenttia yrityksen liikevaihdosta vuonna 2003. Toimenpide-ehdotusten mukaan yrityksen tulisi lisätä yhteistyötä sekä toimittajien että turkistarhojen eli yrityksen osakkeenomistajien kanssa. Lähitulevaisuudessa olisi paikallaan investoiminen asianmukaiseen ja tehokkaaseen jakelun ja kuljetusten suunnittelu- ja seurantajärjestelmään. Itse jakelussa tulisi siirtyä jakelureittien optimointiin ja naiden optimaalisten jakelureittien käyttöön. Tutkimuksen mukaan jakelussa tulee siirtyä joko asiakaskohtaiseen tai osareittien mukaiseen jakeluvalin harvennukseen sesonkiaikavälillä kesäkuu - joulukuu. Jakeluhinnoittelussa on unohdettava nykyinen vyöhykehinnoittelu ja otettava käyttöön tutkimuksen perusteella jakelun todellisia kustannuksia paremmin vastaava ja asiakkaita tasapuolisesti kohteleva hinnoittelumenetelmä. Yrityksen tulisi jatkossa sisäistää jatkuvan kehityksen periaatteet sekä liiketoiminnassaan että jakelutoiminnoissaan.

Pankin arvot päivittäisessä pankkityössä-tapaustutkimus Handelsbanken Suomen aluepankista

Tämän tutkimuksen tavoitteena on selvittää, miten kansainvälisen pankkikonsernin arvoihin perustuva toimintatapa näkyy päivittäisessä pankkityössä Suomen aluepankin alueella. Handelsbankenin toiminta-ajatus perustuu vahvaan yrityskulttuuriin ja arvoihin. Yrityskulttuuri ja arvot ovat yli 30 vuotta vanhoja ja niiden mukaan toimitaan edelleen. Tutkimus sisältää henkilökunnan, asiakkaiden ja pankin johtoryhmään kuuluvan henkilön näkökulmat siitä, mitkä arvot ovat ryhmille tärkeitä ja miten arvoihin perustuva toiminta näkyy päivittäisessä pankkityössä. Rahoitusmarkkinoiden muutos Suomessa mahdollisti ulkomaisten pankkien tulon Suomen pankkimarkkinoille. Handelsbanken tuli markkinoille omalla, kotimaisten pankkien toimintatavasta poikkeavalla toimintamallilla. Paikallisuuteen ja kustannustehokkuuteen perustuva malli on toiminut Ruotsissa jo 1970-luvulta lähtien. 1990-luvulla pankki laajensi toimintaansa muihin pohjoismaihin ja 2000-luvulla ympäri maailman.

Balanced Scorecardin tuottama lisäarvo strategian implementoinnissa

The objective of this study was to define the benefits of using the Balanced Scorecard in strategy implementation in general and evaluate its suitability and potential benefits for a case organization. In the theoretical part of the study, a framework for the benefits of using the Balanced Scorecard in strategy implementation was constructed on the basis of several earlier studies. The framework was also used to assist in the evaluation in the empirical part of the study. The case organization was one business area of a Finnish industrial corporation. The study was carried out before implementing the Balanced Scorecard in the case organization. This study revealed that the Balanced Scorecard can generally benefit the strategy implementation in several ways. It could also be applied to the case organization. The potential benefits that the system can bring to the case organization are to assist standardizing operating methods, to intensify communication and steering and to concretize goal-setting and tracking. Some specific demands were also revealed for the implementation of the Balanced Scorecard.

Sähköisten kuljetustietojen vaikutukset päivittäistavarakaupan pitkässä arvoketjussa

Tutkielman tavoitteena on esittää kustannustehokkaita tapoja lähetystoimintojen ja kuljetustietojen käsittelyyn päivittäistavarakaupan logistiikkakeskuksessa. Tutkielmassa kuvataan case-yrityksen lähettämö- ja kuljetustoimintojen sekä lähtevän tavaravirran seurannan ja rahtilaskutuksen nykytilanne. Tutkimusmenetelmänä on käytetty case-yrityksen avainhenkilöiden teemahaastatteluja sekä erillistä haastattelututkimusta kahdeksalle suurimmalle case-yrityksen käyttämälle kuljetusliikkeelle. Työssä esitellään keskeisimpien kuljetustietojen ja lähettämötoimintojen sähköistämisen edellytyksiä sekä niiden toteutusmahdollisuuksia. Koska lähtevän tavaravirran käsittely manuaalisesti aiheuttaa ylimääräisiä virheitä ja tehottomuutta pitkän arvoketjun eri vaiheissa työllistäen lähettämön, kuljetusliikkeiden, terminaalien ja myymälöiden työntekijöitä, on tutkielmassa esitelty keskeisimmät keinot tehostaa ja automatisoida lähtevien kuljetusyksiköiden käsittelyä. Ratkaisut pohjautuvat lähtevien kuljetusyksiköiden yksilöintiin ja seurantaan. Yksiköiden käsittelyä tehostetaan automatisoimalla yksiköiden tunnistamista ja tiedonsiirtoa. Käytettäviksi työkaluiksi on valittu viivakoodit ja tarvittavat lukijat yksiköiden tunnistamiseen. Sähköisellä rahtikirjalla pyritään paperittomaan lähettämötoimintaan ja sitä kautta automatisoimaan rahtilaskutusta ottamalla käyttöön laskuton maksu. Kuljetustietojen sähköistämisellä voidaan saavuttaa mittavat kustannussäästöt pitkässä arvoketjussa.

Visual performance in preterm infants with brain injuries compared with low-risk preterm infants

Background: Neonatal brain injuries are the main cause of visual deficit produced by damage to posterior visual pathways.While there are several studies of visual function in low-risk preterm infants or older children with brain injuries, research in children of early age is lacking. Aim: To assess several aspects of visual function in preterm infants with brain injuries and to compare them with another group of low-risk preterm infants of the same age. Study design and subjects: Forty-eight preterm infants with brain injuries and 56 low-risk preterm infants. Outcome measures: The ML Leonhardt Battery of Optotypes was used to assess visual functions. This test was previously validated at a post-menstrual age of 40 weeks in newborns and at 30-plus weeks in preterm infants. Results: The group of preterminfants with brain lesions showed a delayed pattern of visual functions in alertness, fixation, visual attention and tracking behavior compared to infants in the healthy preterm group. The differences between both groups, in the visual behaviors analyzed were around 30%. These visual functions could be identified from the first weeks of life. Conclusion: Our results confirm the importance of using a straightforward screening test with preterminfants in order to assess altered visual function, especially in infants with brain injuries. The findings also highlight the need to provide visual stimulation very early on in life.

Análise da distribuição espacial de dose absorvida em próton terapia ocular

OBJETIVO: Propõe-se avaliar os perfis de dose em profundidade e as distribuições espaciais de dose para protocolos de radioterapia ocular por prótons, a partir de simulações computacionais em código nuclear e modelo de olho discretizado em voxels. MATERIAIS E MÉTODOS: As ferramentas computacionais empregadas foram o código Geant4 (GEometry ANd Tracking) Toolkit e o SISCODES (Sistema Computacional para Dosimetria em Radioterapia). O Geant4 é um pacote de software livre, utilizado para simular a passagem de partículas nucleares com carga elétrica através da matéria, pelo método de Monte Carlo. Foram executadas simulações computacionais reprodutivas de radioterapia por próton baseada em instalações pré-existentes. RESULTADOS: Os dados das simulações foram integrados ao modelo de olho através do código SISCODES, para geração das distribuições espaciais de doses. Perfis de dose em profundidade reproduzindo o pico de Bragg puro e modulado são apresentados. Importantes aspectos do planejamento radioterápico com prótons são abordados, como material absorvedor, modulação, dimensões do colimador, energia incidente do próton e produção de isodoses. CONCLUSÃO: Conclui-se que a terapia por prótons, quando adequadamente modulada e direcionada, pode reproduzir condições ideais de deposição de dose em neoplasias oculares.

Simulação e análise dosimétrica de protonterapia e íons de carbono no tratamento do melanoma uveal

OBJETIVO: Este artigo apresenta a avaliação dosimétrica da radioterapia por íons de carbono em comparação à protonterapia. MATERIAIS E MÉTODOS: As simulações computacionais foram elaboradas no código Geant4 (GEometry ANd Tracking). Um modelo de olho discretizado em voxels implementado no sistema Siscodes (sistema computacional para dosimetria em radioterapia) foi empregado, em que perfis de dose em profundidade e curvas de isodose foram gerados e superpostos. Nas simulações com feixe de íons de carbono, distintos valores de energia do feixe foram adotados, enquanto nas simulações com feixe de prótons os dispositivos da linha de irradiação foram incluídos e diferentes espessuras do material absorvedor foram aplicadas. RESULTADOS: As saídas das simulações foram processadas e integradas ao Siscodes para gerar as distribuições espaciais de dose no modelo ocular, considerando alterações do posicionamento de entrada do feixe. Os percentuais de dose foram normalizados em função da dose máxima para um feixe em posição de entrada específica, energia da partícula incidente e número de íons de carbono e de prótons incidentes. CONCLUSÃO: Os benefícios descritos e os resultados apresentados contribuem para o desenvolvimento das aplicações clínicas e das pesquisas em radioterapia ocular por íons de carbono e prótons.

Visual SLAM for 3D large-scale seabed acquisition employing underwater vehicles

This paper presents a novel technique to align partial 3D reconstructions of the seabed acquired by a stereo camera mounted on an autonomous underwater vehicle. Vehicle localization and seabed mapping is performed simultaneously by means of an Extended Kalman Filter. Passive landmarks are detected on the images and characterized considering 2D and 3D features. Landmarks are re-observed while the robot is navigating and data association becomes easier but robust. Once the survey is completed, vehicle trajectory is smoothed by a Rauch-Tung-Striebel filter obtaining an even better alignment of the 3D views and yet a large-scale acquisition of the seabed

Reliability of intraoperative ultrasound in margin status assessment in women undergoing breast conserving surgery

Background: Effective treatment for breast cancer requires accurate preoperative planning, developing and implementing a consistent definition of margin clearance, and using tools that provide detailed real-time intraoperative information on margin status. Intraoperative ultrasound (IOUS) may fulfil these requirements and may offer few advantages that other preoperative localization and intraoperative margin assessment techniques may notPurpose: The goal of the present work is to determine how accurate the intraoperative ultrasound should be to acquire complete surgical excision with negative histological margins in patients undergoing Breast Conservative SurgeryDesign: A diagnostic test study with a cross-sectional design carried out in a tertiary referral hospital in Girona within a Breast Pathology UnitParticipants: Women diagnosed with breast cancer undergoing a Breast Conservative Surgery in the Breast Pathology Unit at Hospital Universitari de Girona Dr. Josep Trueta

Production planning development in global manufacturing company

Larox Corporation is a provider of full service filtration in solid and liquid separation. Larox develops, designs, manufactures and supplies industrial filters. By Larox’s continuous development principle, a project for more efficient production was started. At the same time production planning was taken under review. Aim for this Master’s thesis was to find software designed for production planning purposes replacement for old Microsoft Excel based method. In this Master’s thesis current way of production planning was thoroughly analyzed and improvement targets were specified and also requirements for new software were assigned. Primary requirements for new software were possibility to production scheduling, planning, follow-up and also for long-time capacity planning and tracking. Also one demand was that new software should have data link to Larox’s current ERP-system. Result of this Master’s thesis was to start using Larox’s ERP-system also for production planning purposes. New mode of operation fulfils all requirements which were placed to new system. By using new method of production planning, production planners can get more easier and reliable data than from current system.

Laatukustannusten sisäisen raportoinnin kehittäminen Metso Rautpohjan paperi- ja kartonkikonetehtaassa

Tässä diplomityössä on tarkasteltu Metso Rautpohjan laatukustannustiedon sisäisiä raportointitarpeita ja -mahdollisuuksia päätöksenteon tueksi. Tehty tarkastelu liittyy aiemmin Rautpohjassa luotuun laaduttomuuden kustannusten kirjaus- ja seurantajärjestelmään, jonka avulla kyseisiä kustannuksia on organisaatiossa eritelty muista kustannuksista Baan-tietojärjestelmää käyttäen. Tämän työn tavoitteena oli löytää tapaustutkimuksen keinoin laaduttomuuden kustannuksiin liittyviä sisäisiä tietotarpeita, joihin voitaisiin löytää ratkaisuja Data Warehouse (DW) -tietovarastointi- ja raportointitekniikkaa sekä olemassa olevaa laaduttomuuden kustannustietomassaa 2008 hyödyntäen. Tutkimusta varten Rautpohjan organisaatiosta valittiin kullekin toiminnolle niitä edustavat vastuuhenkilöt, joita haastattelemalla pyrittiin selvittämään sisäisiä tietotarpeita laaduttomuuden kustannuksiin liittyen. Työn tuloksena jokaiselle tutkimukseen osallistuneelle toiminnolle luotiin vähintään yksi raporttipohja, jonka avulla niille voidaan jatkossa tuottaa tarvittavaa, kohdennettua laaduttomuuden kustannustietoa omaan toimintaan liittyen. Laaduttomuuden kustannusten rinnalla tässä työssä tutkittiin myös mahdollisia kehitystarpeita Rautpohjan ympäristökustannuksien seurantaan liittyen. Suuremmassa mittakaavassa tällä työllä on pyritty tukemaan laaduttomuuden kustannusten minimointia paitsi Rautpohjassa, mutta myös Metson linjaorganisaatiossa yleisesti. Raportoinnin perimmäisenä tarkoituksena oli mahdollistaa laaduttomuuden kustannusten taustalla olevien syiden ja tapahtumien analysointi, ja sitä kautta edesauttaa laaduttomuuden kustannusten minimoimiseen tähtäävää kehitystyötä. Metso Rautpohjassa toimiviksi havaittuja laaduttomuuden kustannusten seurantaan ja analysointiin käytettyjä menetelmiä voidaan haluttaessa soveltaa myös muissa Metso-yksiköissä.

RAPD analysis of genetic variability in a multiprovenance base population of Eucalyptus grandis hill ex maiden

This study aimed to evaluate the genetic variability among individuals of a base population of Eucalyptus grandis and to build a molecular marker database for the analyzed populations. The Eucalyptus grandis base population comprised 327 individuals from Coff's Harbour, Atherton and Rio Claro. A few plants came from other sites (Belthorpe MT. Pandanus, Kenilworth, Yabbra, etc.). Since this base population had a heterogeneous composition, the groups were divided according to geographic localization (latitude and longitude), and genetic breeding level. Thus, the influence of those two factors (geographic localization and genetic breeding level) on the genetic variability detected was discussed. The RAPD technique allowed the evaluation of 70 loci. The binary matrix was used to estimate the genetic similarity among individuals using Jaccard's Coefficient. Parametric statistical tests were used to compare within-group similarity of the means. The obtained results showed that the base population had wide genetic variability and a mean genetic similarity of 0.328. Sub-group 3 (wild materials from the Atherton region) showed mean genetic similarity of 0.318. S.P.A. (from Coff's Harbour region) had a mean genetic similarity of 0.322 and was found to be very important for maintenance of variation in the base population. This can be explained since the individuals from those groups accounted for most of the base population (48.3% for it). The base population plants with genetic similarity higher than 0.60 should be phenotypically analyzed again in order to clarify the tendency of genetic variability during breeding programs.

Application of Computational Fluid Dynamics in Modeling Blood Flow in Human Thoracic Aorta

The aim of this study was to simulate blood flow in thoracic human aorta and understand the role of flow dynamics in the initialization and localization of atherosclerotic plaque in human thoracic aorta. The blood flow dynamics in idealized and realistic models of human thoracic aorta were numerically simulated in three idealized and two realistic thoracic aorta models. The idealized models of thoracic aorta were reconstructed with measurements available from literature, and the realistic models of thoracic aorta were constructed by image processing Computed Tomographic (CT) images. The CT images were made available by South Karelia Central Hospital in Lappeenranta. The reconstruction of thoracic aorta consisted of operations, such as contrast adjustment, image segmentations, and 3D surface rendering. Additional design operations were performed to make the aorta model compatible for the numerical method based computer code. The image processing and design operations were performed with specialized medical image processing software. Pulsatile pressure and velocity boundary conditions were deployed as inlet boundary conditions. The blood flow was assumed homogeneous and incompressible. The blood was assumed to be a Newtonian fluid. The simulations with idealized models of thoracic aorta were carried out with Finite Element Method based computer code, while the simulations with realistic models of thoracic aorta were carried out with Finite Volume Method based computer code. Simulations were carried out for four cardiac cycles. The distribution of flow, pressure and Wall Shear Stress (WSS) observed during the fourth cardiac cycle were extensively analyzed. The aim of carrying out the simulations with idealized model was to get an estimate of flow dynamics in a realistic aorta model. The motive behind the choice of three aorta models with distinct features was to understand the dependence of flow dynamics on aorta anatomy. Highly disturbed and nonuniform distribution of velocity and WSS was observed in aortic arch, near brachiocephalic, left common artery, and left subclavian artery. On the other hand, the WSS profiles at the roots of branches show significant differences with geometry variation of aorta and branches. The comparison of instantaneous WSS profiles revealed that the model with straight branching arteries had relatively lower WSS compared to that in the aorta model with curved branches. In addition to this, significant differences were observed in the spatial and temporal profiles of WSS, flow, and pressure. The study with idealized model was extended to study blood flow in thoracic aorta under the effects of hypertension and hypotension. One of the idealized aorta models was modified along with the boundary conditions to mimic the thoracic aorta under the effects of hypertension and hypotension. The results of simulations with realistic models extracted from CT scans demonstrated more realistic flow dynamics than that in the idealized models. During systole, the velocity in ascending aorta was skewed towards the outer wall of aortic arch. The flow develops secondary flow patterns as it moves downstream towards aortic arch. Unlike idealized models, the distribution of flow was nonplanar and heavily guided by the artery anatomy. Flow cavitation was observed in the aorta model which was imaged giving longer branches. This could not be properly observed in the model with imaging containing a shorter length for aortic branches. The flow circulation was also observed in the inner wall of the aortic arch. However, during the diastole, the flow profiles were almost flat and regular due the acceleration of flow at the inlet. The flow profiles were weakly turbulent during the flow reversal. The complex flow patterns caused a non-uniform distribution of WSS. High WSS was distributed at the junction of branches and aortic arch. Low WSS was distributed at the proximal part of the junction, while intermedium WSS was distributed in the distal part of the junction. The pulsatile nature of the inflow caused oscillating WSS at the branch entry region and inner curvature of aortic arch. Based on the WSS distribution in the realistic model, one of the aorta models was altered to induce artificial atherosclerotic plaque at the branch entry region and inner curvature of aortic arch. Atherosclerotic plaque causing 50% blockage of lumen was introduced in brachiocephalic artery, common carotid artery, left subclavian artery, and aortic arch. The aim of this part of the study was first to study the effect of stenosis on flow and WSS distribution, understand the effect of shape of atherosclerotic plaque on flow and WSS distribution, and finally to investigate the effect of lumen blockage severity on flow and WSS distributions. The results revealed that the distribution of WSS is significantly affected by plaque with mere 50% stenosis. The asymmetric shape of stenosis causes higher WSS in branching arteries than in the cases with symmetric plaque. The flow dynamics within thoracic aorta models has been extensively studied and reported here. The effects of pressure and arterial anatomy on the flow dynamic were investigated. The distribution of complex flow and WSS is correlated with the localization of atherosclerosis. With the available results we can conclude that the thoracic aorta, with complex anatomy is the most vulnerable artery for the localization and development of atherosclerosis. The flow dynamics and arterial anatomy play a role in the localization of atherosclerosis. The patient specific image based models can be used to diagnose the locations in the aorta vulnerable to the development of arterial diseases such as atherosclerosis.