New pool of cortical interneuron precursors in the early postnatal dorsal white matter.

The migration of cortical γ-aminobutyric acidergic interneurons has been extensively studied in rodent embryos, whereas few studies have documented their postnatal migration. Combining in vivo analysis together with time-lapse imaging on cortical slices, we explored the origin and migration of cortical interneurons during the first weeks of postnatal life. Strikingly, we observed that a large pool of GAD65-GFP-positive cells accumulate in the dorsal white matter region during the first postnatal week. Part of these cells divides and expresses the transcription factor paired box 6 indicating the presence of local transient amplifying precursors. The vast majority of these cells are immature interneurons expressing the neuronal marker doublecortin and partly the calcium-binding protein calretinin. Time-lapse imaging reveals that GAD65-GFP-positive neurons migrate from the white matter pool into the overlying anterior cingulate cortex (aCC). Some interneurons in the postnatal aCC express the same immature neuronal markers suggesting ongoing migration of calretinin-positive interneurons. Finally, bromodeoxyuridine incorporation experiments confirm that a small fraction of interneurons located in the aCC are generated during the early postnatal period. These results altogether reveal that at postnatal ages, the dorsal white matter contains a pool of interneuron precursors that divide and migrate into the aCC.

Changes in activity of the regulatory glycolytic enzymes and of the pyruvate-dehydrogenase complex during the development of Xenopus laevis.

In this study we investigated the variations of the maximal activities of the rate-controlling glycolytic enzymes (i.e., hexokinase, HK; phosphofructokinase, PFK; pyruvate kinase, PK) and of the pyruvate-dehydrogenase complex (PDHc) during the early embryogenesis of Xenopus laevis (from cleavage through hatching). All the enzymatic assays, using different coupled reactions, were performed spectrophotometrically on cytosolic and mitochondrial fractions. The maximal HK activity increases markedly from neurulation onwards, PFK activity presents a peak around gastrulation, PK activity remains relatively constant throughout the period studied and the highest PDHc activity is observed during cleavage. The specific activities display the same temporal pattern. Furthermore, in the sequence of reactions by which glucose is degraded to form acetyl-CoA, the maximal activities of PFK and PK are not limiting while those of HK and PDHc could be rate-limiting at relatively late developmental stages (hatching).

Water, energy and early postnatal growth in preterm infants.

Non-invasive methods, including stable isotope techniques, indirect calorimetry, nutritional balance and skinfold thickness, have given a new insight into early postnatal growth in neonates. Neonates and premature infants in particular, create an unusual opportunity to study the fluid and metabolic adaptation to extrauterine life because their physical environment can be controlled, fluid and energy balance can be measured and the link between metabolism and the energetics of their postnatal growth can be assessed accurately. Thus the postnatal time course of total body water, heat production, energy cost of growth and composition of weight gain have been quantified in a series of "healthy" low-birth-weight premature infants. These results show that total body water is remarkably stable between postnatal days 3-21. Energy expenditure and heat production rates increase postnatally from mean values of 40 kcal/kg/day during the first week to 60 kcal/kg/day in the third week. An apparent energy balance deficit of 180 kcal/kg can be ascribed to premature delivery. The cost of protein metabolism is the highest energy demanding process related to growth. The fact that nitrogen balance becomes positive within 72 h after birth places the newborn in a transitional situation of dissociated balance between energy and protein metabolism during early postnatal growth: skinfold thickness, dry body mass and fat decrease, while there is a gain in protein and increase in supine length. This particular situation ends during the second postnatal week and soon thereafter the rate of weight gain matches statural growth. The goals of the following review are to summarize data on total body water and energy metabolism in premature infants and to discuss how they correlate with physiological aspects of early postnatal growth.

Personality traits, behavioral and psychological symptoms and cognitive decline in patients at an early stage of Alzheimer's disease

The aim of this doctoral thesis was to study personality characteristics of patients at an early stage of Alzheimer's disease (AD), and more specifically to describe personality and its changes over time, and to explore its possible links with psychological and symptoms (BPS) and cognitive level. The results were compared to those of a group of participants without cognitive disorder through three empirical studies. In the first study, the findings showed significant personality changes that follow a specific trend in the clinical group. The profil of personality changes showed an increase in Neuroticism and a decrease in Extraversion, Openess to experiences, and Conscientiousness over time. The second study highlighted that personality and BPS occur early in the cours of AD. Recognizing them as possible precoce signs of neurodegeneration may prove to be a key factor for early detection and intervention. In the third study, a significant association between personality changes and cognitive status was observed in the patients with incipient AD. Thus, changes in Neuroticism and Conscientiousness were linked with cognitive deterioration, whereas decreased Openness to experiences and Conscientiousness over time predicted loss of independence in daily functioning. Other well-known factors such as age, education level or civil status were taken into account to predict cognitive decline. The three studies suggested five important implications: (1) cost-effective screening should take into account premorbid and specific personality changes; (2) psycho-educative interventions should provide information on the possible personality changes and BPS that may occur at the beginning of the disease; (3) using personality traits alongside other variables in the future studies on prevention might help to better understand AD's etiology; (4) individual treatment plans (psychotherapeutic, social, and pharmacological) might be adapted to the specific changes in personality profiles; (5) more researches are needed to study the impact of social-cultural and lifestyle variables on the development of AD.

Planning and control of internal development projects in a fast changing environment: Case study

Tutkimuksen tarkoituksena on kuvata ja ymmärtää kuinka sisäisiä kehityshankkeita voidaan hallita onnistuneesti kun toimitaan nopeasti muuttuvassa ympäristössä. Tutkimus kuvailee etenkin projekteille tärkeitä menestymistekijöitä, kuten suunnittelu, kontrollointi ja päätöksenteko. Tutkimus selvittää yleisimmät ongelma-alueet case-organisaation sisäisten kehityshankkeiden hallinnassa. Tutkimus on luonteeltaan laadullinen tutkimus, jossa tutkimusmenetelmänä on käytetty tapaustutkimusta. Empiirisessa osassa käsittellään case-organisaation sisäisiä informaatioteknologia-hankkeita (IT) ja uusien konseptien kehityshankkeita (NCD). iSisäisten kehityshankkeiden erilaisuuden ymmärtäminen oli tutkimuksen tärkein tulos. Tutkimuksen empiirinen osio osoitti sen, että epävarmuudella on erittäin suuri vaikutus projektihallintaan sekä projektin kontrollointiin. Case-organisaation IT-projektien onnistuminen riippuu organisaatiomuu-toksen onnistumisesta. Asiakkaisiin ja markkinoihin liittyvät epävarmuudet ovat vaikuttavimmat NCD projektien epävarmuuksista. Näillä epävarmuuk-sil­la on vaikutusta projektihallintaan jonka myötä NCD projektit juuttuvat useim­mi­ten noidankehiin tai ne lopetetaan jo aikaisessa vaiheessa.

L'immunoscintigraphie par les anticorps monoclonaux radiomarqués. Evolution d'une méthode de diagnostic du cancer et espoir d'une nouvelle forme de thérapie [Immunoscintigraphy using radio-labeled monoclonal antibodies. Development of a method of cancer diagnosis and hopes for a new form of therapy].

Personal results are presented to illustrate the development of immunoscintigraphy for the detection of cancer over the last 12 years, from the early experimental results in nude mice grafted with human colon carcinoma to the most modern form of immunoscintigraphy applied to patients, using I123 labeled Fab fragments from monoclonal anti-CEA antibodies detected by single photon emission computerized tomography (SPECT). The first generation of immunoscintigraphy used I131 labeled, immunoadsorbent purified, polyclonal anti-CEA antibodies and planar scintigraphy, as the detection system. The second generation used I131 labeled monoclonal anti-CEA antibodies and SPECT, while the third generation employed I123 labeled fragments of monoclonal antibodies and SPECT. The improvement in the precision of tumor images with the most recent forms of immunoscintigraphy is obvious. However, we think the usefulness of immunoscintigraphy for routine cancer management has not yet been entirely demonstrated. Further prospective trials are still necessary to determine the precise clinical role of immunoscintigraphy. A case report is presented on a patient with two liver metastases from a sigmoid carcinoma, who received through the hepatic artery a therapeutic dose (100 mCi) of I131 coupled to 40 mg of a mixture of two high affinity anti-CEA monoclonal antibodies. Excellent localisation in the metastases of the I131 labeled antibodies was demonstrated by SPECT and the treatment was well tolerated. The irradiation dose to the tumor, however, was too low at 4300 rads (with 1075 rads to the normal liver and 88 rads to the bone marrow), and no evidence of tumor regression was obtained. Different approaches for increasing the irradiation dose delivered to the tumor by the antibodies are considered.

Epigenetic alterations and constitutive Wnt signaling are early events in the progression from Barrett's esophagus to esophageal adenocarcinoma

SUMMARY Barrett's esophagus (BE) is an acquired condition in which the normal squamous epithelium in the distal esophagus is replaced by a metaplastic columnar epithelium, as a complication of chronic gastroesophageal reflux. The clinical significance of this disease is its associated predisposition to esophageal adenocarcinoma (EAC). EAC is a highly lethal disease. Better understanding of the pathogenesis of columnar metaplasia and its progression to cancer might allow the identification of biomarkers that can be used for early diagnosis, which will improve the patient survival. In this study, an improved protocol for methylation-sensitive single-strand conformation analysis, which is used to analyze promoter methylation, is proposed and a methylation-sensitive dot blot assay is described, which allows a rapid, easy, and sensitive detection of promoter methylation. Both methods were applied to study the methylation pattern of the APC promoter in histologically normal appearing gastric mucosa. The APC promoter showed monoallelic methylation, and because the methylated allele differed between the different gastric cell types, this corresponded to allelic exclusion. The APC methylation pattern was frequently altered in noimal gastric mucosa associated with neoplastic lesions, indicating that changes in the pattern of promoter methylation might precede the development of neoplasia, without accompanying histological manifestations. An epigenetic profile of 10 genes important in EAC was obtained in this study; 5 promoter genes (APC, TIMP3, TERT, CDKN2A and SFRP1) were found to be hypermethylated in the tumors. Furthermore, the promoter of APC, TIMP3 and TERT was frequently methylated in BE samples from EAC patients, but rarely in BE samples that did not progress to EAC. These three biomarkers might therefore be considered as potential predictive markers for increased EAC risk. Analysis of Wnt pathway alterations indicated that WNT2 ligand is overexpressed as early as the low-grade dysplastic stage and downregulation by promoter methylation of the SFRP1 gene occurrs already in the metaplastic lesions. Moreover, loss of APC expression is not the only factor involved in the activation of the Wnt pathway. These results indicate that a variety of biologic, mostly epigenetic events occurs very early in the carcinogenesis of BE. This new information might lead to improved early diagnosis of EAC and thus open the way to a possible application of these biomarkers in the prediction of increased EAC risk progression. RESUME L'oesophage de Barrett est une lésion métaplasique définie par le remplacement de la muqueuse malpighienne du bas oesophage par une muqueuse cylindrique glandulaire, suite à une agression chronique par du reflux gastro-esophagien. La plus importante signification clinique de cette maladie est sa prédisposition au développement d'un adénocarcinome. Le pronostic de l'adénocarcinome sur oesophage de Barrett est sombre. Seule une meilleure compréhension de la pathogenèse de l'épithélium métaplasique et de sa progression néoplasique permettrait l'identification de biomarqueurs pouvant être utilisés pour un diagnostic précoce ; la survie du patient serait ainsi augmentée. Dans cette étude, un protocole amélioré pour l'analyse de la méthylation par conformation simple brin est proposé. De plus, une technique d'analyse par dot blot permettant une détection rapide, facile et sensible de la méthylation d'un promoteur est décrite. Les deux méthodes ont été appliquées à l'étude de la méthylation du promoteur du gène APC dans des muqueuses gastriques histologiquement normales. Le promoteur APC a montré une méthylation monoallélique et, parce que les allèles méthylés différaient entre les différents types de cellules gastriques, celle-ci correspondait à une méthylation allélique exclusive. La méthylation d'APC a été trouvée fréquemment altérée dans la muqueuse gastrique normale associée à des lésions néoplasiques. Ceci indique que des changements dans la méthylation d'un promoteur peuvent précéder le développement d'une tumeur, et cela sans modification histologique. Un profil épigénétique des adénocarcinomes sur oesophage de Barrett a été obtenu dans cette étude. Cinq promoteurs (APC, TIMP3, TERT, CDKN2A et SFRP1) ont été trouvés hyperméthylés dans les tumeurs. Les promoteurs d'APC, TIMP3 et TERT étaient fréquemment méthylés dans l'épithélium métaplasique proche d'un adénocarcinome et rarement dans l'épithélium sans évolution néoplasique. Ces trois biomarkers pourraient par conséquent être considérés comme marqueur prédicatif d'un risque accru de développer une tumeur. L'analyse des altérations de la voie Wnt a montré que WNT2 est surexprimé déjà dans des dysplasies de bas-grade et que la dérégulation de SFRP1 par méthylation de son promoteur intervenait dans les lésions métaplasiques. Une perte d'expression d'APC n'est pas le seul facteur impliqué dans l'activation de cette voie. Ces résultats montrent qu'une grande diversité d'événements biologiques, principalement épigénétiques, surviennent très tôt lors de la carcinogenèse de l'oesophage de Barrett. Ces nouveaux éléments pourraient améliorer le diagnostic précoce et rendre possible l'application de ces biomarqueurs dans la prédiction d'un risque accru de développer un adénocarcinome sur un oesophage de Barrett.

Russian transition in the early 21st century

Tässä tutkimuksessa käsitellään Venäjän talouden kehitystä uudella vuosituhannella. Kylmän sodan aikaan Neuvostoliitto oli suurvalta, jonka asema perustui sotilasmahtiin. Sotateollisuuden konversio palvelemaan nykytarpeita ei ole ollut helppo tehtävä. Vuoden 1998 talouskriisin jälkeen elintaso on toipunut verraten nopeasti, mikä on nähtävissä tarkastellessa kotitalouksien kulutusrakenteita, joita käsitellään tarkemmin luvussa 2. Siirtymätalouksissa vaihtotaseen vajeet ovat yleisiä, mutta luonnonrikkauksiensa ansiosta Venäjän vaihtotaseet ovat olleet huomattavan ylijäämäisiä, mitä pohditaan luvussa 3. Vaihtotaseen ylijäämien heijatusvaikutus on ollut Venäjän rooli pääomien nettoviejänä. Venäjän investointikertymä onedelleen erittäin vaatimaton suhteutettuna maan kehitysvaiheeseen. Jokaisessa menestyksekkäässä taloudessa investoinnit ovat pitkän aikavälintaloudellisen menestyksen avaintekijä. Venäjän erityispiirteitä tähän liittyen on kuvattu luvussa 4. Raportti päättyy talouden nykytilanteen analyysiin (luvut 5 ja 6).

Supporting knowledge creation and sharing in the early phases of the strategic innovation process

The driving forces of technology and globalization continuously transform the business landscape in a way which undermines the existing strategies and innovations of organizations. The challenge for organizations is to establish such conditions where they are able to create new knowledge for innovative business ideas in interaction between other organizations and individuals. Innovation processes continuously need new external stimulations and seek new ideas, new information and knowledge locating more and more outside traditional organizational boundaries. In several studies, the early phases of the innovation process have been considered as the most critical ones. During these phases, the innovation process can emerge or conclude. External knowledge acquirement and utilization are noticed to be important at this stage of the innovation process giving information about the development of future markets and needs for new innovative businessideas. To make it possible, new methods and approaches to manage proactive knowledge creation and sharing activities are needed. In this study, knowledge creation and sharing in the early phases of the innovation process has been studied, and the understanding of knowledge management in the innovation process in an open and collaborative context advanced. Furthermore, the innovation management methods in this study are combined in a novel way to establish an open innovation process and tested in real-life cases. For these purposes two complementary and sequentially applied group work methods - the heuristic scenario method and the idea generation process - are examined by focusing the research on the support of the open knowledge creation and sharing process. The research objective of this thesis concerns two doctrines: the innovation management including the knowledge management, and the futures research concerning the scenario paradigm. This thesis also applies the group decision support system (GDSS) in the idea generation process to utilize the converged knowledge during the scenario process.

Peduncle and fruit yield, in six cropping seasons, of early dwarf cashew tree clones irrigated with different water regimes

The objective of this work was to evaluate peduncle and fruit yield in clone MS 076 and in a clonal population of drip-irrigated, early dwarf cashew trees propagated by layering, in six cropping seasons. In order to meet the increased water requirements of the crop resulting from plant growth and development, irrigation during the dry season was performed daily according to the following water regime: 15 min/plant/day during the 1st year, 30 min/plant/day during the 2nd year, 45 min/plant/day during the 3rd year and 60 min/plant/day during all subsequent years. Water was supplied by one drip emitter/plant, at an (adjustable) flow rate of 36 L/h.The research was carried out in Fortaleza-Ceará, Brazil, and a random block design was utilized, with five replicates and split-plots. The clones were assigned to plots and the cropping seasons were considered as subplots. The clonal population was superior to the clone only with regard to number of nut shells (NNS), and solely in the first season. The clone was superior to the population as to NNS and peduncle yield (PY) in the second season, and also with regard to the three evaluated traits - NNS, PY, and nut shell yield, in the last three cropping seasons.

Differences in phasic development rate amongst wheat cultivars independent of responses to photoperiod and vernalization. A viewpoint of the intrinsic earliness hypothesis

Differences amongst wheat cultivars in the rate of reproductive development are largely dependent on differences in their sensitivity to photoperiod and vernalization. However, when these responses are accounted for, by growing vernalized seedlings under long photoperiods, cultivars can still differ markedly in time to ear emergence. Control of rate of development by this ‘third factor’ has been poorly understood and is variously referred to as intrinsic earliness, earliness in the narrow sense, basic vegetative period, earliness per se, and basic development rate. Certain assumptions are made in the concept of intrinsic earliness. They are that differences in intrinsic earliness (i) are independent of the responses of the cultivars to photoperiod and vernalization, (ii) apply only to the length of the vegetative period up to floral initiation (as suggested by several authors), (iii) are maintained under different temperatures, measured either in days or degree days. As a consequence of this, the ranking of cultivars (from intrinsically early to intrinsically late) must be maintained at different temperatures. This paper, by the re-analysis of published data, examines the extent to which these assumptions can be supported. Although it is shown that intrinsic earliness operates independently of photoperiod and vernalization responses, the other assumptions were not supported. The differences amongst genotypes in time to ear emergence, grown under above-optimum vernalization and photoperiod (that is when the response to these factors is saturated), were not exclusively due to parallel differences in the length of the vegetative phase, and the length of the reproductive phase was independent of that of the vegetative phase. Thus, it would be possible to change the relative allocation of time to vegetative and reproductive periods with no change in the full period to ear emergence. The differences in intrinsic earliness between cultivars were modified by the temperature regime under which they were grown, i.e. the difference between cultivars (both considering the full phase to ear emergence or some sub-phases) was not a constant amount of time or thermal time at different temperatures. In addition, in some instances genotypes changed their ranking for ‘intrinsic earliness’ depending on the temperature regime. This was interpreted to mean that while all genotypes are sensitive to temperature they differ amongst themselves in the extent of that sensitivity. Therefore, ‘intrinsic earliness’ should not be considered as a static genotypic characteristic, but the result of the interaction between the genotype and temperature. Intrinsic earliness is therefore likely to be related to temperature sensitivity. Some implications of these conclusions for plant breeding and crop simulation modelling are discussed.

Modelling leaf development in Oxalis latifolia

This study was carried to develop functions that could explain the growth of Oxalis latifolia, in both early stages and throughout the season, contributing to the improvement of its cultural control. Bulbs of the Cornwall form of O. latifolia were buried at 1 and 8 cm in March 1999 and 2000. Samples were destructive at fixed times, and at each time the corresponding BBCH scale codes as well as the absolute number of growing and adult leaves were noted. Using the absolute number of adult leaves (transformed to percentages), a Gaussian curve of three parameters that explains the growth during the season (R2=0.9355) was developed. The BBCH scale permitted the fit of two regression lines that were accurately adjusted for each burial depth (R2=0.9969 and R2=0.9930 respectively for 1 and 8 cm). The best moment for an early defoliation in Northern Spain could be calculated with these regression lines, and was found to be the second week of May. In addition, it was observed that a burial depth of 8 cm does not affect the growing pattern of the weed, but it affects the number of leaves they produce, which decreases to less than a half of those produced at 1 cm.

Selected Aspects Related to Pre-development Stages of International Software projects. Case of Finland and Russia

The question of Pilot Project creation, due to support pre-development stage of software product elaboration, nowadays might be used as an approach, which allows improving the whole scheme of information technology project running. This subject is not new, but till now no model has been presented, which gives deep description of this important stage on the early phase of project. This Master's Thesis represents the research's results and findings concerning the pre-development study from the Software Engineering point of view. The aspects of feasibility study, pilot prototype developments are analyzed in this paper. As the result, the technique of Pilot Project is formulated and scheme has been presented. The experimental part is focused on particular area Pilot Project scheme's implementation- Internationally Distributed Software projects. The specific characteristic, aspects, obstacles, advantages and disadvantages are considered on the example of cross border region of Russia and Finland. The real case of Pilot Project technique implementation is given.

Physical layer development in third generation protocol software architecture

Diplomityön tavoitteena oli kehittää kolmannen sukupolven fyysistä protokollakerrosta matkapuhelimen ohjelmistoarkkitehtuurille. Kolmannen sukupolven matkapuhelinjärjestelmät ovat aikaisempia järjestelmiä monimutkaisempia. Ohjelmiston koon ja monimutkaisuuden sekä aikataulujen kiireellisyyden vuoksi on tullut tarve ottaa käyttöön formaaleja menetelmiä ohjelmiston kehitystyöhön. Formaalit kuvauskielet mahdollistavat tarkan, yksiselitteisen ja simuloitavissa olevan järjestelmäkuvauksen muodostamisen. Fyysinen protokollakerros tarjoaa tiedon siirtoa ylemmille protokollakerroksille. Tämän tiedonsiirron hallinta vaatii protokollakerrosten välistä viestinvälitystä. Formaaleja kuvauskieliä käyttämällä voidaan viestinvälityksen toteutusta automatisoida ja siinä tarvittavaa logiikkaa havainnollistaa. Työssä suunniteltiin, toteutettiin ja testattiin ylempien protokollakerrosten kanssa kommunikoivaa osaa fyysisestä protokollakerroksesta. Tuloksena saatiin solunvalintatoiminnallisuuden vaatiman kommunikoinnin ja tilakoneen toteutus ohjelmistoarkkitehtuurissa. Ohjelmistonkehityksen alkuvaiheiden havaittiin olevan fyysisen kerroksen suorituskyvyn kannalta merkittävässä asemassa, koska tällöin viestinvälityksen optimointi on helpointa. Formaalit kuvauskielet eivät ole sellaisenaan täysin soveltuvia tarkoin määritellyn ohjelmistoarkkitehtuurin osien kehitykseen.

Rapid Sequestration of Leishmania mexicana by Neutrophils Contributes to the Development of Chronic Lesion.

The protozoan Leishmania mexicana parasite causes chronic non-healing cutaneous lesions in humans and mice with poor parasite control. The mechanisms preventing the development of a protective immune response against this parasite are unclear. Here we provide data demonstrating that parasite sequestration by neutrophils is responsible for disease progression in mice. Within hours of infection L. mexicana induced the local recruitment of neutrophils, which ingested parasites and formed extracellular traps without markedly impairing parasite survival. We further showed that the L. mexicana-induced recruitment of neutrophils impaired the early recruitment of dendritic cells at the site of infection as observed by intravital 2-photon microscopy and flow cytometry analysis. Indeed, infection of neutropenic Genista mice and of mice depleted of neutrophils at the onset of infection demonstrated a prominent role for neutrophils in this process. Furthermore, an increase in monocyte-derived dendritic cells was also observed in draining lymph nodes of neutropenic mice, correlating with subsequent increased frequency of IFNγ-secreting T helper cells, and better parasite control leading ultimately to complete healing of the lesion. Altogether, these findings show that L. mexicana exploits neutrophils to block the induction of a protective immune response and impairs the control of lesion development. Our data thus demonstrate an unanticipated negative role for these innate immune cells in host defense, suggesting that in certain forms of cutaneous leishmaniasis, regulating neutrophil recruitment could be a strategy to promote lesion healing.