Circadian glomerular function: from physiology to molecular and therapeutical aspects.

Life on earth is rhythmic by essence due to day/night alternation, and many biological processes are also cyclic. The kidney has a special role in the organism, controlling electrolytes and water balance, blood pressure, elimination of metabolic waste and xenobiotics and the production of several hormones. The kidney is submitted to changes throughout 24 h with periods of intense activity followed by calmer periods. Filtration, reabsorption and secretion are the three components determining renal function. Here, we review circadian changes related to glomerular function and proteinuria and emphasize the role of the clock in these processes.

Cancer chronotherapeutics: experimental, theoretical, and clinical aspects.

The circadian timing system controls cell cycle, apoptosis, drug bioactivation, and transport and detoxification mechanisms in healthy tissues. As a consequence, the tolerability of cancer chemotherapy varies up to several folds as a function of circadian timing of drug administration in experimental models. Best antitumor efficacy of single-agent or combination chemotherapy usually corresponds to the delivery of anticancer drugs near their respective times of best tolerability. Mathematical models reveal that such coincidence between chronotolerance and chronoefficacy is best explained by differences in the circadian and cell cycle dynamics of host and cancer cells, especially with regard circadian entrainment and cell cycle variability. In the clinic, a large improvement in tolerability was shown in international randomized trials where cancer patients received the same sinusoidal chronotherapy schedule over 24h as compared to constant-rate infusion or wrongly timed chronotherapy. However, sex, genetic background, and lifestyle were found to influence optimal chronotherapy scheduling. These findings support systems biology approaches to cancer chronotherapeutics. They involve the systematic experimental mapping and modeling of chronopharmacology pathways in synchronized cell cultures and their adjustment to mouse models of both sexes and distinct genetic background, as recently shown for irinotecan. Model-based personalized circadian drug delivery aims at jointly improving tolerability and efficacy of anticancer drugs based on the circadian timing system of individual patients, using dedicated circadian biomarker and drug delivery technologies.

Biological aspects of Harmonia axyridis in comparison with Cycloneda sanguinea and Hippodamia convergens

The objective of this work was to evaluate the development, survival, reproductive capacity, and longevity of the Asian ladybug Harmonia axyridis in comparison with Cycloneda sanguinea and Hippodamia convergens. Coccinellid larvae and adults were fed daily with Schizaphis graminum. Ten couples of each species were isolated for evaluation of the adult phase. The duration of the larval stage of H. axyridis is the longest (10.2 days) and its adults are the heaviest (29.7 mg) compared with C. sanguinea and H. convergens. The three species showed similar percentages of survival during the developmental stages. An average of 82% of C. sanguinea, H. axyridis, and H. convergens larvae reached adulthood, which indicates that temperature (25°C) and the offered prey are favorable to coccinellid development. Harmonia axyridis produces a higher total number of eggs per female (1,029.2) than the other evaluated species. However, H. axyridis, which lives for an average of 147.2 days, does not show a significantly greater longevity than C. sanguinea (87.2 days) and H. convergens (134.3 days).

DFMA- Analysis and Aspects of Applying Internet Based Collaborative Design for Axial Eccentric Oil-Pump Design

The integrated system of design for manufacturing and assembly (DFMA) and internet based collaborative design are presented to support product design, manufacturing process, and assembly planning for axial eccentric oil-pump design. The presented system manages and schedules group oriented collaborative activities. The design guidelines of internet based collaborative design & DFMA are expressed. The components and the manufacturing stages of axial eccentric oil-pump are expressed in detail. The file formats of the presented system include the data types of collaborative design of the product, assembly design, assembly planning and assembly system design. Product design and assembly planning can be operated synchronously and intelligently and they are integrated under the condition of internet based collaborative design and DFMA. The technologies of collaborative modelling, collaborative manufacturing, and internet based collaborative assembly for the specific pump construction are developed. A seven-security level is presented to ensure the security of the internet based collaborative design system.

Les aspects sanitaires du travail de la police auprès des consommateurs de drogues

Voir aussi version en allemand: Gesundheitliche Aspekte der Polizeiarbeit im Drogenbereich.

Topological aspects of DNA function and protein folding.

The Topological Aspects of DNA Function and Protein Folding international meeting provided an interdisciplinary forum for biological scientists, physicists and mathematicians to discuss recent developments in the application of topology to the study of DNA and protein structure. It had 111 invited participants, 48 talks and 21 posters. The present article discusses the importance of topology and introduces the articles from the meeting's speakers.

Harmonization ofsignificant environmental aspects and their risk assessment in UPM paper and pulp mills

Työn tavoite onharmonisoida yhtenäiset rakenteet UPM:n paperi- ja sellutehtaiden merkittävilleympäristönäkökohdille sekä niiden ympäristöriskienhallintajärjestelmille. Näin saavutetaan yhteneväiset tavoitteet ja analysointikeinot yrityksen yksiköille. Harmonisointiprosessi on osa koko yrityksen ympäristöhallintajärjestelmän kehittämistä. Ja konsernin EMS -prosessi puolestaan konvergoi konsernin integroidun johtamisjärjestelmän kehitystä. Lisäksi työn tapaustutkimuksessa selvitettiin riskienhallintajärjestelmien integroitumispotentiaalia. Sen avulla saavutettaisiin paremmin suuren yrityksen synergia-etuja ja vuorovaikutteisuutta toimijoiden kesken, sekä parannettaisiin riskienhallintajärjestelmän mukautuvuutta ja käytettävyyttä. Työssä käsitellään kolmea esimerkkiä, joiden pohjalta tehdään esitys harmonisoiduille merkittäville ympäristönäkökohdille sekä riskienhallintajärjestelmien parametreille. Tutkimusongelmaa lähestytään haastattelujen, kirjallisuuden, yrityksen PWC:llä teettämän selvityksen sekä omien päätelmien avulla. Lisäksi työssä esitetään ympäristöhallintajärjestelmän tehokkuuden todentaminen ympäristösuorituskyvyn muuttujiin suhteutettuna. Pohjana jatkuvan kehityksen päämäärälle on organisaatio-oppiminen, niin yksittäisen työntekijän, tiimien kuin eri yksiköiden kesken. Se antaa sysäyksen aineettoman omaisuuden, kuten ympäristö-osaamisen, hyödyntämiseen parhaalla mahdollisella tavalla. Tärkeimpinä lopputuloksina työssä ovat ehdotukset harmonisoiduille merkittäville ympäristönäkökohdille sekä ympäristöriskienhallintajärjestelmän määritetyille komponenteille. Niitä ovat määritelmät ja skaalat riskien todennäköisyydelle, seurauksille sekä riskiluokille. Työn viimeisenä osana luodaan pohja tapaustutkimuksen avulla Rauman tehtaan jätevedenpuhdistamon kahden erilaisen riskienhallintajärjestelmän integroitumiselle.

Evolutionary aspects of population structure for molecular and quantitative traits in the freshwater snail Radix balthica.

Detecting the action of selection in natural populations can be achieved using the QST-FST comparison that relies on the estimation of FST with neutral markers, and QST using quantitative traits potentially under selection. QST higher than FST suggests the action of directional selection and thus potential local adaptation. In this article, we apply the QST-FST comparison to four populations of the hermaphroditic freshwater snail Radix balthica located in a floodplain habitat. In contrast to most studies published so far, we did not detect evidence of directional selection for local optima for any of the traits we measured: QST calculated using three different methods was never higher than FST. A strong inbreeding depression was also detected, indicating that outcrossing is probably predominant over selfing in the studied populations. Our results suggest that in this floodplain habitat, local adaptation of R. balthica populations may be hindered by genetic drift, and possibly altered by uneven gene flow linked to flood frequency.

Unexplored aspects of bureaucratic autonomy: a state of the field and ways forward

This article first provides a selective overview of the literature on bureaucratic autonomy and identifies different approaches to this topic. The second section discusses three major sets of open questions, which will be tackled in the contributions to this special issue: the subjective, dynamic and relational nature of autonomy; the complex linkages between tasks, organizational forms, and national path dependencies on the one hand and autonomy and performance on the other hand; and the interplay between autonomy, accountability and democratic legitimacy.