Kassanhallintak��yt��nn��t Suomen kunnissa

Kassanhallintakirjallisuus on pitk��lti normatiivista tai yksitt��isi�� kohteita ja niiden kassanhallinnanosa-alueita tarkastelevaa case-tutkimusta. Sen sijaan kassanhallintaa laajalla tutkimuskohdejoukolla strategia- ja j��rjestelm��valintojen n��k��kulmasta tarkastelevia tutkimuksia on tehty vain v��h��n. T��m�� suomalaista kuntakentt���� tarkastelevaeksploratiivinen tutkimus antaa kuvan rakenne-, strategia- ja j��rjestelm��valinnoista, joita kunnat ovat painottaneet kassanhallinnassaan vuosina 2000 - 2002. Tutkimuksen metodologisena viitekehyksen�� k��ytetty kontingenssil��hestymistapaan pohjautuva konfiguratiivinen systeemimalli mahdollisti suuren tutkimuskohdejoukonstrategia- ja j��rjestelm��k��yt��nt��jen erojen kvantitatiivisen analysoinnin. Ryhmittelyanalyysin avulla tutkimusdatasta muodostui nelj�� strategia- ja j��rjestelm��painotuksiltaan toisistaan eroavaa kuntaryhm����, ja tutkimustulokset osoittivat kuntien kassanhallintak��yt��nt��jen olevan hyvin samankaltaisia yksityissektorin vastaaviin k��yt��nt��ihin verrattuna; my��s julkissektorin kassanhallinnassa painotetaan kustannustehokkuutta. Kustannustehokkuusstrategian rinnalla vastaajakunnat painottivat sijoitus-, lainanhoito- ja riskienhallintastrategioita sek�� em. strategioiden toteuttamista tukevia rakenne- ja j��rjestelm��valintoja. My��s pienempienkuntien havaittiin tukeutuneen samoihin strategia- ja j��rjestelm��painotuksiin kuin isommat kunnat, vaikka esim. j��rjestelmien k��yt��nn��n tietohallintaratkaisuissa saattaa esiinty�� kuntakoosta johtuvia eroja. Lis��ksi joustavuusstrategian painoarvo osana kuntien kassanhallintastrategioita oli suuri. T��m�� on johdonmukaista, sill�� kassapositioiden ennakoimattomat muutokset edellytt��v��t nopeaa p����t��ksentekoa. Kustannustehokkuusajattelulla, kassanhoitokokonaisuuden ymm��rt��misell�� ja uusien kassanhoitotekniikoiden sek�� rahoitusinstrumenttien selektiivisell�� k��yt��ll�� on mahdollista vaikuttaa kuntien rahoituksenhoidon nettokustannuksiin.

Els assentaments de les edats del bronze, ib��rica i romana d"Els Llirians del Mas i Les Torres (Sal��s de Pallars, Pallars Juss��)

[cat] En els anys 2003 i 2004 una intervenci�� arqueol��gica preventiva en el terme de Sal��s de Pallars va permetre documentar seixanta estructures excavades al subs��l. La majoria de les estructures foren identificades com a sitges, per�� tamb�� es documentaren cubetes i fosses de diversa funci��, algunes utilitzades com a sepultures. L"estudi dels materials recuperats, complementats per datacions radiocarb��niques, indiquen dos per��odes cronol��gics: el bronze inicial i l"etapa ib��rica plena, als quals s"ha d"afegir una ��nica estructura que pertany a comen��aments de l"Imperi rom��. Les dades obtingudes informen sobre les pr��ctiques de les comunitats agr��coles assentades en el sector meridional de la comarca del Pallars Juss�� en tres moments hist��rics diferents. [eng]In 2003 and 2004 a Preventive Archaeological Excavation was done in the locality of Sal��s de Pallars. This allowed to catalogue the sixty structures found in the subsoil. Most of the structures were identified as silos, but we also documented basins and pits with different functions, some used as graves. The study of the recovered materials, supported by a radiocarbon analysis technique, ages this around two chronological periods: the Early Bronze Age and Iberian Period. We must add a third period to classify a single structure that belongs to the Early Roman Empire. The obtained results provide us information about the farming methods used by the communities placed in the southern Region of the Pallars Juss�� during the three different historical moments.

Tiedon strateginen johtaminen viranomaisessa. Case: Rahoitustarkastu

Tutkimuksen tarkoituksena oli selvitt���� tiedon strategista johtamista Rahoitustarkastuksessa. Tavoitteena oli muodostaa k��sitys siit��, mitk�� ovat ne kriittiset tekij��t ja n��k��kohdat, jotka ovat hyv��n tietojohtamisen edellytyksi��. Tutkimus toteutettiin kvalitatiivisena tapaustutkimuksena, ja siin�� perehdyttiin mm. Rahoitustarkastuksen johdon dokumentoituihin tietojohtamisen linjauksiin. Tutkimus osoitti, ett�� tiedon strategisessa johtamisessa on t��rke����, ett�� tietostrategia on kytketty tiiviisti toimintastrategiaan. Lis��ksi organisaation tulisi m����ritell�� tietojohtamisen prosessinsa ja tukea n��it�� mm. tarjoamalla oikeat olosuhteet, resurssit ja tekniikat ja infrastruktuuri. Kumppanuuksien ja verkostojen hallitsemiseksi tulisi olla selke��t periaatteet. Tutkimuksen tuloksena kehitettiin Rahoitustarkastukselle ennakoivan tietojohtamisen malli. Tutkimustuloksista tehtiin my��s se johtop����t��s, ett�� tietostrategian voisi koostaa er����nlaiseksi kokoomastrategiaksi tai sateenvarjoksi organisaation johtamisk��yt��nn��ille. Kokoomastrategia kytkisi nykyisin irrallaan olevat tietojohtamiseenkin vaikuttavat alastrategiat yhdeksi kokonaisuudeksi ja pakottaisi tarkastelemaan n��it�� alastrategioita my��s tietojohtamisen n��k��kulmasta.

Elinkaarianalyysin soveltaminen k��ytt��kustannuslaskennassa ja kilpailijavertailussa

The aim of this master���s thesis is to develop a calculation form that can be utilized in studying life cycle costs of different products. This research will especially focus on competing products with different cost structures. The calculation form introduced here will then be applied to calculate the operation costs of green mowers in terms of the life cycle method.The research contains an introduction to the field of study and its specific features. The main questions are how to construct a frame of reference and how to find an effective way to combine life cycle assessment and calculation with management accounting. The empirical part of the research concentrated on studying operation costs of green mowers in different working situations. The results were critically analyzed and the effectivity of the new calculation form was estimated.The present study shows that this new method is effective in giving information on life cycle costs. The results concerning the green mowers were not simple but depended on several factors. In any case it is possible to say that the new type of the green mower is very competitive against the traditional green mowers.

Analysis of SKI-1/S1P prodomain provides insight on maturation and activation of SKI-1/S1P zymogen

SKI-l/SlP protease is a member of the proprotein convertase family, with several functions in cellular metabolism and homeostasis. It is responsible for the processing of several cellular substrates, including ATF6, SREBPs, and GlcNAc-1- phosphotranspherase. Furthermore, SKI-1/SlP is also responsible for maturation of arenavirus surface glycoprotein into GP1 and GP2 subunits. This processing is a strict requirement in order to achieve fully mature and fusion-competent virions. Furthermore, SKI-1/SlP itself is synthesized as an inactive zymogen, requiring sequential autocatalytic processing at several sites (B'/B and C) in its prodomain in order to mature and become fully active. Our project focused on the analysis of SKI- 1/S1P prodomain in the biogenesis of the active enzyme. In this context we have additionally developed and characterized a novel cell-based sensor for assessment of cellular activity of the enzyme, with a potential application in screening for novel SKI- 1/S1P inhibitors. In a first aim we have analysed the relevance of cleavage motifs found in the enzyme prodomain. Using molecular and biochemistry tools we have identified and characterized a novel C' maturation site. Furthermore, we found that SKI-1/SlP autoprocessing results in intermediates whose catalytic domain remains associated with prodomain fragments of different lengths. Contrasting with other proprotein convertases, incompletely matured intermediates of SKI-1/SlP exhibit full catalytic activity toward selected substrates. In a second aim, we turned our attention to the structural basis of SKI-1/SlP N- terminus assisted folding. Studying the folding and activity of prodomain-truncated forms of the enzyme we found that a minimal folding unit is contained in the AB region. Deletion of the BC sequence affected auto-maturation but not folding, and partial activity was retained. However, the BC region seemed required for complete and full activity. Phylogenetic analyses showed that the AB sequence is highly conserved, while the BC fragment is variable in sequence and length. Specifically, replacement of the human prodomain with that of Drosophila, resulted in a fully mature and active chimeric enzyme, suggesting an evolution process of SKI-1/SlP prodomain towards a more complex arrangement and steps of activation. Overall, the additional data we have produced might provide fundamental knowledge crucial for the development of novel SKI-1/SlP inhibitors while also providing new SKI- 1/S1P variants with potential use in crystallization purpose. -- SKI-l/SlP est une prot��ase membre de la famille des proprot��ines convertases (PCs), avec plusieurs fonctions dans le m��tabolisme cellulaire et de l'hom��ostasie. Il est responsable pour la maturation de plusieurs substrats cellulaires, y compris ATF6, SREBPs et GlcNAc-1-phosphotranspherase. SKI-l/SlP est ��galement responsable pour la maturation de la glycoprot��ine des ar��navirus, une exigence stricte pour atteindre des virions infectieuse. Synth��tis�� comme un zymog��ne inactif, SKI-l/SlP n��cessite d'un traitement autocatalytique s��quentiel sur plusieurs sites (B'/B et C) de son prodomaine afin de devenir pleinement active. Notre projet ��tait ax�� sur l'analyse de SKI-l/SlP prodomaine dans la biogen��se de l'enzyme. Dans ce contexte, nous avons d��velopp�� un nouveau senseur-cellulaire pour l'��valuation de l'activit�� de l'enzyme. Ce dernier pourrait avoir une potentielle application dans l'identification de nouveaux inhibiteurs de SKI-l/SlP. Premi��rement, nous avons analys�� la pertinence des motifs de clivage trouv��s dans le prodomaine de l'enzyme. En utilisant des outils mol��culaires et biochimiques, nous avons identifi�� et caract��ris�� un nouveau site de maturation (C'). Aussi, nous avons constat�� que la maturation de SKI-l/SlP a des interm��diaires dont le domaine catalytique reste associ�� �� des fragments du prodomaine de diff��rentes longueurs. Contrastant avec d'autres PCs, les interm��diaires partiellement matures de SKI-1 / SIP pr��sentent une activit�� catalytique compl��te envers des substrats sp��cifiques. Dans un deuxi��me but nous avons tourn�� notre attention sur la base structurelle du pliage de SKI-l/SlP assist�� par son N-terminus: En ��tudiant l'activit�� et pliage des formes tronqu��es dans le prodomaine de l'enzyme, nous avons constat�� qu'une unit�� de pliage minimale est contenue dans la r��gion de l'AB. La suppression de la s��quence d'auto-BC affecte la maturation mais pas le pliage, et l'activit�� partielle est maintenue. Cependant, la r��gion BC semble n��cessaire pour une activit�� compl��te. Les analyses phylog��n��tiques ont montr�� que la s��quence AB est fortement conserv��e, tandis que le fragment de BC est variable en longueur et en s��quence. En particulier, le remplacement du prodomaine humain avec celui de la drosophile, a donn�� lieu �� une enzyme chim��rique compl��tement mature et active. Sugg��rant un processus d'��volution du prodomaine vers un arrangement et des mesures d'activation plus complexe. Globalement, ces donnees suppl��mentaires augment les connaissances fondamentales cruciales pour le d��veloppement de nouveaux inhibiteurs de SKI-1/ SIP, tout en offrant de nouvelles variantes SKI-1 / SIP dans le but d'obtenir la structure cristallographique de l'enzyme.

Microtubule Associated Protein 1b (MAP1B) Is a Marker of the Microtubular Cytoskeleton in Podocytes but Is Not Essential for the Function of the Kidney Filtration Barrier in Mice.

Podocytes are essential for the function of the kidney glomerular filter. A highly differentiated cytoskeleton is requisite for their integrity. Although much knowledge has been gained on the organization of cortical actin networks in podocyte's foot processes, less is known about the molecular organization of the microtubular cytoskeleton in primary processes and the cell body. To gain an insight into the organization of the microtubular cytoskeleton of the podocyte, we systematically analyzed the expression of microtubule associated proteins (Maps), a family of microtubules interacting proteins with known functions as regulator, scaffold and guidance proteins. We identified microtubule associated protein 1b (MAP1B) to be specifically enriched in podocytes in human and rodent kidney. Using immunogold labeling in electron microscopy, we were able to demonstrate an enrichment of MAP1B in primary processes. A similar association of MAP1B with the microtubule cytoskeleton was detected in cultured podocytes. Subcellular distribution of MAP1B HC and LC1 was analyzed using a double fluorescent reporter MAP1B fusion protein. Subsequently we analyzed mice constitutively depleted of MAP1B. Interestingly, MAP1B KO was not associated with any functional or structural alterations pointing towards a redundancy of MAP proteins in podocytes. In summary, we established MAP1B as a specific marker protein of the podocyte microtubular cytoskeleton.

Vitaminas lipossol��veis em alimentos: uma abordagem anal��tica

This study concerns certain problems inherent to the determination of fat-soluble vitamins in food, from extraction methods to identification and quantification. The discussion involves the main official and unofficial extraction methods coupled with spectrophotometric and HPLC techniques in which vitamins samples are obtained through liquid-liquid-solid and liquid-liquid-solid-solid extraction, indispensable to the analytical separation of different chemical compounds with vitamin functions. A saponification stage, possibly coupled with supercritical fluid extraction appears to be mandatory in the determination of vitamins A and E in their alcoholic forms. Alternative identification and quantification procedures are outlined: biological and chemical assays, analytical separations by HPLC (normal and reversed-phase), UV detection (all fat-soluble vitamins) and fluorescence detection (retinoids and tocopherols). Automation from sample preparation to quantification stages increases the data acquisition rate.

Virtualitzaci�� de servidors. Avantatges. Implantaci�� en una PIME real

En la societat d���avui dia, les empreses depenen en gran part dels seus recursos inform��tics. La seva capacitat de superviv��ncia i innovaci�� en el mercat actual, on la competitivitat ��s cada dia m��s forta, passa per una infraestructura inform��tica que els permeti, no nom��s desplegar i implantar ordinadors i servidors de manera r��pida i eficient sin�� que tamb�� les protegeixi contra parades del sistema inform��tic, problemes amb servidors, caigudes o desastres f��sics de hardware. Per evitar aquests problemes inform��tics susceptibles de poder parar el funcionament d���una empresa es va comen��ar a treballar en el camp de la virtualitzaci�� inform��tica amb l���objectiu de poder trobar solucions a aquests problemes a la vegada que s���aprofitaven els recursos de hardware existents d���una manera m��s ��ptim a i eficient, reduint aix�� tamb�� el cost de la infraestructura inform��tica. L���objectiu principal d���aquest treball ��s veure en primer pla la conversi�� d���una empresa real amb una infraestructura inform��tica del tipus un servidor f��sic -una funci�� cap a una infraestructura virtual del tipus un servidor f��sic -varis servidors virtual -v��ries funcions. Analitzarem l���estat actual de l���empresa, servidors i funcions, adquirirem el hardware necessari i farem la conversi�� de tots els seus servidors cap a una nova infraestructura virtual. Faig especial atenci�� a les explicacions de perqu�� utilitzo una opci�� i no un altre i tamb�� procuro sempre donar v��ries opcions. Igualment remarco en quadres verds observacions a tenir en compte complement��ries al que estic explicant en aquell moment, i en quadres vermells temes en els que s���ha de posar especial atenci�� en el moment en que es fan. Finalment, un cop feta la conversi��, veurem els molts avantatges que ens ha reportat aquesta tecnologia a nivell de fiabilitat, estabilitat, capacitat de toler��ncia a errades, capacitat de r��pid desplegament de noves m��quines, capacitat de recuperaci�� del sistema i aprofitament de recursos f��sics

Role and regulatory mechanisms of heat shock factor 2

Protein homeostasis is essential for cells to prosper and survive. Various forms of stress, such as elevated temperatures, oxidative stress, heavy metals or bacterial infections cause protein damage, which might lead to improper folding and formation of toxic protein aggregates. Protein aggregation is associated with serious pathological conditions such as Alzheimer���s and Huntington���s disease. The heat shock response is a defense mechanism that protects the cell against protein-damaging stress. Its ancient origin and high conservation among eukaryotes suggest that the response is crucial for survival. The main regulator of the heat shock response is the transcription factor heat shock factor 1 (HSF1), which induces transcription of genes encoding protective molecular chaperones. In vertebrates, a family of four HSFs exists (HSF1-4), with versatile functions not only in coping with acute stress, but also in development, longevity and cancer. Thus, knowledge of the HSFs will aid in our understanding on how cells survive suboptimal circumstances, but will also provide insights into normal physiological processes as well as diseaseassociated conditions. In this study, the function and regulation of HSF2 have been investigated. Earlier gene inactivation experiments in mice have revealed roles for HSF2 in development, particularly in corticogenesis and spermatogenesis. Here, we demonstrate that HSF2 holds a role also in the heat shock response and influences stress-induced expression of heat shock proteins. Intriguingly, DNA-binding activity of HSF2 upon stress was dependent on the presence of intact HSF1, suggesting functional interplay between HSF1 and HSF2. The underlying mechanism for this phenomenon could be configuration of heterotrimers between the two factors, a possibility that was experimentally verified. By changing the levels of HSF2, the expression of HSF1-HSF2 heterotrimer target genes was altered, implementing HSF2 as a modulator of HSF-mediated transcription. The results further indicate that HSF2 activity is dependent on its concentration, which led us to ask the question of how accurate HSF2 levels are achieved. Using mouse spermatogenesis as a model system, HSF2 was found to be under direct control of miR-18, a miRNA belonging to the miR-17~92 cluster/Oncomir-1 and whose physiological function had remained unclear. Investigations on spermatogenesis are severely hampered by the lack of cell systems that would mimic the complex differentiation processes that constitute male germ cell development. Therefore, to verify that HSF2 is regulated by miR-18 in spermatogenesis, a novel method named T-GIST (Transfection of Germ cells in Intact Seminiferous Tubules) was developed. Employing this method, the functional consequences of miR-18-mediated regulation in vivo were demonstrated; inhibition of miR- 18 led to increased expression of HSF2 and altered the expression of HSF2 target genes Ssty2 and Speer4a. Consequently, the results link miR-18 to HSF2-mediated processes such as germ cell maturation and quality control and provide miR-18 with a physiological role in gene expression during spermatogenesis.Taken together, this study presents compelling evidence that HSF2 is a transcriptional regulator in the heat shock response and establishes the concept of physical interplay between HSF2 and HSF1 and functional consequences thereof. This is also the first study describing miRNA-mediated regulation of an HSF.

���IT���S ALL RIGHT���. Multimodal rightward spatial bias modified by age and praxis

The general goal of the present work was to study whether spatial perceptual asymmetry initially observed in linguistic dichotic listening studies is related to the linguistic nature of the stimuli and/or is modality-specific, as well as to investigate whether the spatial perceptual/attentional asymmetry changes as a function of age and sensory deficit via praxis. Several dichotic listening studies with linguistic stimuli have shown that the inherent perceptual right ear advantage (REA), which presumably results from the left lateralized linguistic functions (bottom-up processes), can be modified with executive functions (top-down control). Executive functions mature slowly during childhood, are well developed in adulthood, and decline as a function of ageing. In Study I, the purpose was to investigate with a cross-sectional experiment from a lifespan perspective the age-related changes in top-down control of REA for linguistic stimuli in dichotic listening with a forced-attention paradigm (DL). In Study II, the aim was to determine whether the REA is linguistic-stimulus-specific or not, and whether the lifespan changes in perceptual asymmetry observed in dichotic listening would exist also in auditory spatial attention tasks that put load on attentional control. In Study III, using visual spatial attention tasks, mimicking the auditory tasks applied in Study II, it was investigated whether or not the stimulus-non-specific rightward spatial bias found in auditory modality is a multimodal phenomenon. Finally, as it has been suggested that the absence of visual input in blind participants leads to improved auditory spatial perceptual and cognitive skills, the aim in Study IV was to determine, whether blindness modifies the ear advantage in DL. Altogether 180-190 right-handed participants between 5 and 79 years of age were studied in Studies I to III, and in Study IV the performance of 14 blind individuals was compared with that of 129 normally sighted individuals. The results showed that only rightward spatial bias was observed in tasks with intensive attentional load, independent of the type of stimuli (linguistic vs. non-linguistic) or the modality (auditory vs. visual). This multimodal rightward spatial bias probably results from a complex interaction of asymmetrical perceptual, attentional, and/or motor mechanisms. Most importantly, the strength of the rightward spatial bias changed as a function of age and augmented praxis due to sensory deficit. The efficiency of the performance in spatial attention tasks and the ability to overcome the rightward spatial bias increased during childhood, was at its best in young adulthood, and decreased as a function of ageing. Between the ages of 5 and 11 years probably at first develops movement and impulse control, followed by the gradual development of abilities to inhibit distractions and disengage attention. The errors especially in bilateral stimulus conditions suggest that a mild phenomenon resembling extinction can be observed throughout the lifespan, but especially the ability to distribute attention to multiple targets simultaneously decreases in the course of ageing. Blindness enhances the processing of auditory bilateral linguistic stimuli, the ability to overcome a stimulus-driven laterality effect related to speech sound perception, and the ability to direct attention to an appropriate spatial location. It was concluded that the ability to voluntarily suppress and inhibit the multimodal rightward spatial bias changes as a function of age and praxis due to sensory deficit and probably reflects the developmental level of executive functions.

Muutoksen toteuttaminen suuressa teollisuusyrityksess�� - Case Hartwall Lahti

Muutos on kiinte�� osa t��m��n p��iv��n organisaatioiden toimintaa. T��m�� asettaa haasteita niin muutoksen johtamiselle kuin esimiesten osaamiselle. T��m��n ty��n tavoitteena oli selvitt����, kuinka suuressa teollisessa tuotanto-organisaatiossa toteutettuun toimintatapamuutokseen vaikutetaan johtamisen keinoin ja miten eri henkil��st��ryhm��t kokevat muutoksen. N��iden pohjalta tunnistettiin ne johtamisen osa-alueet ja muut tekij��t, joita tulee kehitt���� seuraavassa muutosprosessissa ja sen suunnittelussa. Ty��ss�� tutkitaan toteutettua muutosta viiden eri n��k��kulman kautta suorittamalla teemahaastattelut johdon, esimiesten ja ty��ntekij��iden edustajille. Teemat, joihin t��m�� tutkimus pureutui olivat; uuden toimintamallin merkitt��vin sis��lt��, muutoksen v��ltt��m��tt��myys, muutosviestint��, muutoksen toteuttaminen ja muutoksen seuranta. Ty��n johtop����t��ksin�� ja yhteenvetona voidaan todeta, ett�� muutoksen suunnitteluun kannattaa panostaa runsaasti ajallisia resursseja ja sitouttaa henkil��it�� eri organisaatiotasoilta. Muutosviestint�� on oleellinen osa muutoksen onnistumisessa ja sen osaamista tulisi kehitt����, sek�� luoda ymm��rryst�� viestinn��n t��rkeydest�� muutoksessa. Keskijohto sek�� ty��ntekij��iden suorat esimiehet ovat ne ryhm��t, joiden ymm��rrys toteutettavasta muutoksesta on kriittinen tekij�� ja joille t��ytyy erityisesti varmistaa riitt��v�� muutosjohtamisen osaaminen.

Herpes simplex virus type 1 (HSV-1) pathogenesis and HSV gene therapy of experimental autoimmune encephalomyelitis

The aim of this thesis was to develop new herpes simplex virus (HSV) vectors for gene therapy of experimental autoimmune encephalomyelitis (EAE), the principal model of multiple sclerosis (MS), and to study the pathogenesis of wild-type HSV-1 and HSV-1 vectors in vivo. By introducing potential immunomodulatory factors into mice with EAE we strived to develop therapies and possibly find molecules improving recovery from EAE. We aimed at altering the immune response by inducing favorable Th2-type cytokines, thus shifting the immune response from a Th1- or a Th17-response. Our HSV vector expressing interleukin (IL)-5 modulated the cytokine responses, decreased inflammation and alleviated EAE. The use of a novel method, bacterial artificial chromosome (BAC), for engineering recombinant HSV facilitated the construction of a new vector expressing leukemia inhibitory factor (LIF). LIF is a neurotropic cytokine with broad functions in the central nervous system (CNS). LIF promotes oligodendrocyte maturation and decreases demyelination and oligodendrocyte loss. The BAC-derived HSV-LIF vector alleviated the clinical symptoms, induced a higher number of oligodendrocytes and modulated T cell responses. By administering HSV via different infection routes, e.g. peripherally via the nose or eye, or intracranially to the brain, the effect of the immune response on HSV spread at different points of the natural infection route was studied. The intranasal infection was an effective delivery route of HSV to the trigeminal ganglion and CNS, whereas corneal infection displayed limited spread. The corneal and intranasal infections induced different peripheral immune responses, which might explain the observed differences in viral spread.

Stochastic approximation methods in stochastic optimization

Stochastic approximation methods for stochastic optimization are considered. Reviewed the main methods of stochastic approximation: stochastic quasi-gradient algorithm, Kiefer-Wolfowitz algorithm and adaptive rules for them, simultaneous perturbation stochastic approximation (SPSA) algorithm. Suggested the model and the solution of the retailer's profit optimization problem and considered an application of the SQG-algorithm for the optimization problems with objective functions given in the form of ordinary differential equation.

Conditioned medium from activated spleen cells supports the survival of rat retinal cells in vitro

Cytokines are a heterogeneous group of molecules that have been associated with several functions in the nervous system, such as survival and differentiation of neuronal and glial cells. In the present study, we demonstrated that conditioned medium from spleen cells activated with concanavalin A increased neuritogenesis and survival of retinal cells, as measured by biochemical and morphological criteria. Our data showed that conditioned medium induced a five-fold increase in the amount of protein after 120 h in vitro. This effect was not inhibited by the blockade of voltage-dependent L-type calcium channels with 5.0 ��M nifedipine. However, the use of an intracellular calcium chelator (15.0 ��M BAPTA-AM) inhibited this effect. Our results support the idea that factors secreted by activated lymphocytes, such as cytokines, can modulate the maintenance and the differentiation of rat retinal cells in vitro, indicating a possible role of these molecules in the development of retinal cells, as well as in its protection against pathological conditions

Protein folding: a perspective for biology, medicine and biotechnology

At the present time, protein folding is an extremely active field of research including aspects of biology, chemistry, biochemistry, computer science and physics. The fundamental principles have practical applications in the exploitation of the advances in genome research, in the understanding of different pathologies and in the design of novel proteins with special functions. Although the detailed mechanisms of folding are not completely known, significant advances have been made in the understanding of this complex process through both experimental and theoretical approaches. In this review, the evolution of concepts from Anfinsen's postulate to the "new view" emphasizing the concept of the energy landscape of folding is presented. The main rules of protein folding have been established from in vitro experiments. It has been long accepted that the in vitro refolding process is a good model for understanding the mechanisms by which a nascent polypeptide chain reaches its native conformation in the cellular environment. Indeed, many denatured proteins, even those whose disulfide bridges have been disrupted, are able to refold spontaneously. Although this assumption was challenged by the discovery of molecular chaperones, from the amount of both structural and functional information now available, it has been clearly established that the main rules of protein folding deduced from in vitro experiments are also valid in the cellular environment. This modern view of protein folding permits a better understanding of the aggregation processes that play a role in several pathologies, including those induced by prions and Alzheimer's disease. Drug design and de novo protein design with the aim of creating proteins with novel functions by application of protein folding rules are making significant progress and offer perspectives for practical applications in the development of pharmaceuticals and medical diagnostics.