Extracellular-signal-regulated kinase 5 modulates the antioxidant response by transcriptionally controlling Sirtuin 1 expression in leukemic cells.

Cancer cell metabolism differs from that of non-transformed cells in the same tissue. This specific metabolism gives tumor cells growing advantages besides the effect in increasing anabolism. One of these advantages is immune evasion mediated by a lower expression of the mayor histocompatibility complex class I molecules. The extracellular-signal-regulated kinase-5 regulates both mayor histocompatibility complex class I expression and metabolic activity. However, the mechanisms underlying are largely unknown. We show here that extracellular-signal-regulated kinase-5 regulates the transcription of the NADH(+)-dependent histone deacetylase silent mating type information regulation 2 homolog 1 (Sirtuin 1) in leukemic Jurkat T cells. This involves the activation of the transcription factor myocyte enhancer factor-2 and its binding to the sirt1 promoter. In addition, extracellular-signal-regulated kinase-5 is required for T cell receptor-induced and oxidative stress-induced full Sirtuin 1 expression. Extracellular-signal-regulated kinase-5 induces the expression of promoters containing the antioxidant response elements through a Sirtuin 1-dependent pathway. On the other hand, down modulation of extracellular-signal-regulated kinase-5 expression impairs the anti-oxidant response. Notably, the extracellular-signal-regulated kinase-5 inhibitor BIX02189 induces apoptosis in acute myeloid leukemia tumor cells without affecting T cells from healthy donors. Our results unveil a new pathway that modulates metabolism in tumor cells. This pathway represents a promising therapeutic target in cancers with deep metabolic layouts such as acute myeloid leukemia.

Work Organization Practices for Lean Production: A Study in Spanish and Brazilian Manufacturers

This work aims to discuss particular work organization practices in human resources reported as successful by companies adopting lean production principles, and investigate them through real examples observed on manufacturing plants in Spain and Brazil. A set of work organization practices was previously established by one of the authors, through interviews with practitioners of lean production and review of the literature. A series of visits and informal interviews at Spanish and Brazilian automotive parts manufacturers that follow lean production were conducted to verify that the set of policies are indeed practiced.

RFID-tekniikan käyttö betonielementtien tunnistamiseen

RFID on 2000-luvulla yleisesti saatavilla tullut tekniikka erilaisten kohteiden tunnistamiseen. RFID-tekniikassa tunnistamiseen käytetään pienikokoisia tunnisteita, joiden tietosisältö pystytään lukemaan langattomasti ilman näköyhteyttä tarkoitukseen soveltuvalla lukulaitteella. Tunnisteet ovat halpoja ja yksinkertaisia. Yleensä ne eivät sisällä omaa virtalähdettä, vaan ne toimivat ainoastaan lukulaitteen luoman kentän voimalla. Tässä työssä tutkitaan RFID-tekniikan soveltuvuutta betonista valmistettujen rakennuselementtien tunnistamiseen. Ympäristön vaikutukset tekniikan käyttöön tutkitaan ja selvitetään, mitkä ovat parhaat toimintatavat elementtien tunnistamiseen nämä vaikutukset huomioon ottaen. Työssä esitellään ensin RFID-tekniikan toimintaperiaatteet sekä tunnisteiden ja lukulaitteiden rakenne. Tunnisteiden jaottelu erilaisten ominasisuuksien perusteella käydään läpi ja sovellusalan kannalta tärkeimmät standardit esitellään. Käytännön osuudessa esitellään RFID-tekniikan soveltamista betonista valmistettujen rakennuselementtien tunnistamiseen. Työssä esitellään saavutetut mittaustulokset sekä betonielementtien tunnistamiseen ja tietojen hallintaan toteutetun järjestelmän rakenne.

Important role of ventromedial hypothalamic carnitine palmitoyltransferase-1a in the control of food intake

Carnitine palmitoyltransferase-1 (CPT-1) liver isoform or CPT-1a is implicated in CNS control of food intake. However, the exact brain nucleus site(s) in mediating this action of CPT-1a has not been identified. In this report, we assess the role of CPT-1a in hypothalamic ventromedial nucleus (VMN). We stereotaxically injected an adenoviral vector containing CPT-1a coding sequence into the VMN of rats to induce overexpression and activation of CPT-1a. The VMN-selective activation of CPT-1a induced orexigenic effect, suggesting CPT-1a in the VMN is involved in the central control of feeding. Intracerebroventricular administration of etomoxir, a CPT-1 inhibitor, decreases food intake. Importantly, in the animals with VMN-overexpression of a CPT-1a mutant that antagonizes the CPT-1 inhibition by etomoxir, the anorectic response to etomoxir was attenuated. This suggests that VMN is involved in mediating the anorectic effect of central inhibition of CPT-1a. In contrast, Arc overexpression of the mutant did not alter etomoxir-induced inhibition of food intake, suggesting that Arc CPT-1a does not play significant roles in this anorectic action. Furthermore, in the VMN, CPT-1a appears to act downstream of hypothalamic malonyl-CoA action of feeding. Finally, we show that in the VMN, CPT-1 activity altered in concert with fasting and refeeding states, supporting a physiological role of CPT-1a in mediating the control of feeding. Taking together, CPT-1a in the hypothalamic VMN appears to play an important role in the central control of food intake. VMN-selective modulation of CPT-1a activity may therefore be a promising strategy in controlling food intake and maintaining normal body weight.

Determining, Balancing and Controlling of Pitch and White Pitch at Stora Enso Kabel Production Line 4

Työn ensimmäisenä tarkoituksena oli kartoittaa kiinteä-neste ja neste-neste uuttomenetelmillä pihkan ja valkopihkan määrä Stora Enso Kabelin tuotantolinja 4:llä. Työn kannalta oli myöstärkeää saada selvyys saostumien koostumuksesta. Lopullinen päämäärä oli automatisoida fiksatiivin annostelu uuden, jatkuvatoimisen märänpäänanalysaattorin avulla. Mäntyosuuden kasvattaminen hiokemassassa lisää hydrofobisten partikkeleiden lukumäärää, minkä uskotaan lisäävän saostumariskiä. Työtä varten kehitetty neste-neste uuttomenetelmä, jota ei ole liiemmin paperiteollisuudessa käytetty, voi olla hyvä menetelmä lipofiilisten komponenttien määrän arviointiin tietyssä määrässä massa- tai prosessivesinäytettä. Virtaussytometri-menetelmän avulla tutkittiin pihka- tai valkopihkapartikkeleiden määrää ja kokojakaumaa eri prosessinäytteissä. Virtaussytometri-menetelmällä mitattujen valkopihkapartikkeleiden lukumäärän ja päällystetyn hylyn saostimen suodoksen sameuden välille löytyiselvä korrelaatio. Fiksatiivimäärän vaikutusta päällystetyn hylyn saostimen suodoksen sameuteen tutkittiin koeajojaksolla, jossa fiksatiivin annostelua säädettiin käsin. Käytetyt annosmäärät eivät riittäneet sameuden pitämiseen tasaisena matalalla tasolla.

Characterization of rue extract and its potential for controlling rice blast

Abstract: The objective of this work was to purify and standardize the rue (Ruta graveolens) extract and evaluate its effect on Magnaporthe oryzae as an alternative to the integrated management of rice blast. The drug was characterized, the liquid extract was obtained, and the methodology for quantifying the standard markers psoralen and bergapten was validated. Rue extract and the markers, solely or in combination, were assayed in vitro, as well as in greenhouse conditions, for their ability to suppress leaf blast, by the evaluation of mycelial growth, conidial germination, and appressorium formation. Rue extract inhibited M. oryzae mycelial growth (100%), conidial germination (LD50=0.237 mg), and the appressorium formation (LD50=0.121 mg); besides, the extract reduced leaf blast severity by 80.84%. Fluorescence microscopy showed that rue extract did not damage M. oryzae cell wall and plasma membrane, indicating another mode of action. Rue extract has a great potential for controlling rice leaf blast.

In-line Monitoring of Precipitation Process using Raman Spectroscopy and ATR-FTIR

Polymorfian jatkuva seuranta saostuksessa on hyödyllistä suunnittelun ja kidetuotteen ominaisuuksien sekä kiteytystä seuraavan jatkoprosessoinnin kannalta. Tässä diplomityössä on tutkittu L-glutamiinihapon kahden (- ja ß) polymorfimuodon liukoisuuden riippuvuutta pH:sta ja lämpötilasta.Tulokseksi saatiin, että kummankin polymorfin liukoisuus kasvoi sekä pH:ta ettälämpötilaa kasvatettaessa. ¿¿muodon liukoisuus oli korkeampi kuin ß-muodon liukoisuus valituilla pH-arvoilla eri lämpötiloissa. Lisäksi seurattiin puolipanostoimisen saostuksen aikana 1-litraisella laboratoriokiteyttimellä muodostuvan kiteisen polymorfiseoksen koostumusta hyödyntäen in-line Raman-spektroskopiaa. Myös liuoksen pH-muutosta seurattiin sekä liuoksen koostumusta ATR FTIR-spektroskopian (Attenuated Total Reflection Fourier Transform Infrared Spectrometer) avulla. Tutkittavina muuttujina olivat mm. sekoitusintensiteetti, sekoitintyyppi, reaktanttien (natriumglutamaatti ja rikkihappo) konsentraatiot sekä syötetyn rikkihapon syöttökohta kiteyttimessä. Työhön sisältyi 36 koetta ja osa kokeista toistettiin tulosten oikeellisuuden tarkistamiseksi. Inline-mittaustulosten verifioimiseksi kidenäytteet analysoitiin myös käyttämällä konfokaali Raman-mikroskooppia. Kidemorfologiaa tutkittiin SEM-kuvien (Scanning Eletronic Microscope) avulla. Työ osoitti, että Raman-spektroskopia on joustava ja luotettava menetelmä saostusprosessin jatkuvaan seurantaan L-glutamiinihapolla. Alhaiset lähtöainepitoisuudet tuottivat pääasiassa ¿¿muotoa, kun taas alhainen sekoitusteho edisti ß-muodon muodostumista. Syöttökohta vaikutti merkittävästi polymorfiaan. Kun rikkihapon syöttökohta oli epäideaalisesti sekoitetulla vyöhykkeellä, nousi ylikylläisyystaso korkeaksi ja päätuote oli tällöin ß-muotoa. 6-lapainen vinolapaturbiini (nousukulma 45o) ja 6-lapainen levyturbiini eivät merkittävästi poikenneet toisistaan muodostuvien polymorfien osalta.

Causes of health expenditure growth : the predominance of changes in medical practices over population ageing

The increase in total health care expenditures in France can be explained by three distinct factors : the purely demographic effect (namely, the increase in the proportion of elderly people, given that health expenditure is an increasing function of age) ; the changes in morbidity at a given age ; the changes in practices, for a given age and morbidity level (e.g technological progress). The aim of this paper is basically to disentangle, evaluate and interpret the respective effects of these three factors. [Extrait introduction p. 3]

Project controlling and risk management in German machine and plant engineering industry

Tutkielman tavoitteena on määritellä projektikontrolloinnin ja - riskijohtamisen roolit ja toiminnot saksalaisissa kone- ja tehdassuunnitteluteollisuusyrityksissä. Tämä on kvalitatiivinen tutkielma, jossa käytetään voimakkaasti kuvailevia metodeita. Materiaali tutkimuksen empiiriseen osaan kerättiin kyselykaavakkeen avulla. Kyselykaavakkeiden tulokset käsiteltiin Microsoft Office Access- ohjelmalla ja analysoitiin Microsoft Office Excel- ohjelmalla ja Pivot table- työkalun avulla. Tutkimustulokset osoittavat, että asianmukaisessa projektikontrollointi- ja riskijohtamismetodien käytössä ja käyttötiheydessä esiintyy puutteita saksalaisissa kone- ja tehdassuunnitteluteollisuusyrityksissä. Tehostamalla ja keskittymällä enemmän projektikontrollointi- ja riskijohtamismetodeihin ja prosesseihin sekä projektien että yritysten suorituskyky paranisi.

Promoting good practices for handling nanomaterials : an international wiki project

As production and use of nanomaterials in commercial products grow it is imperative to ensure these materials are used safely with minimal unwanted impacts on human health or the environment. Foremost among the populations of potential concern are workers who handle nanomaterials in a variety of occupational settings, including university laboratories, industrial manufacturing plants and other institutions. Knowledge about prudent practices for handling nanomaterials is being developed by many groups around the world but may be communicated in a way that is difficult for practitioners to access or use. The GoodNanoGuide is a collaborative, open-access project aimed at creating an international forum for the development and discussion of prudent practices that can be used by researchers, workers and their representatives, occupational safety professionals, governmental officials and even the public. The GoodNanoGuide is easily accessed by anyone with access to a web browser and aims to become a living repository of good practices for the nanotechnology enterprise. Interested individuals are invited to learn more about the GoodNanoGuide at http://goodnanoguide.org.

Arabidopsis Basic Helix-Loop-Helix Transcription Factors MYC2, MYC3, and MYC4 Regulate Glucosinolate Biosynthesis, Insect Performance, and Feeding Behavior.

Arabidopsis thaliana plants fend off insect attack by constitutive and inducible production of toxic metabolites, such as glucosinolates (GSs). A triple mutant lacking MYC2, MYC3, and MYC4, three basic helix-loop-helix transcription factors that are known to additively control jasmonate-related defense responses, was shown to have a highly reduced expression of GS biosynthesis genes. The myc2 myc3 myc4 (myc234) triple mutant was almost completely devoid of GS and was extremely susceptible to the generalist herbivore Spodoptera littoralis. On the contrary, the specialist Pieris brassicae was unaffected by the presence of GS and preferred to feed on wild-type plants. In addition, lack of GS in myc234 drastically modified S. littoralis feeding behavior. Surprisingly, the expression of MYB factors known to regulate GS biosynthesis genes was not altered in myc234, suggesting that MYC2/MYC3/MYC4 are necessary for direct transcriptional activation of GS biosynthesis genes. To support this, chromatin immunoprecipitation analysis showed that MYC2 binds directly to the promoter of several GS biosynthesis genes in vivo. Furthermore, yeast two-hybrid and pull-down experiments indicated that MYC2/MYC3/MYC4 interact directly with GS-related MYBs. This specific MYC-MYB interaction plays a crucial role in the regulation of defense secondary metabolite production and underlines the importance of GS in shaping plant interactions with adapted and nonadapted herbivores.

Introducing Basic Systematic Requirements Engineering Practices in Small Organizations with an Easy to Adopt Method

Requirements-relatedissues have been found the third most important risk factor in software projects and as the biggest reason for software project failures. This is not a surprise since; requirements engineering (RE) practices have been reported deficient inmore than 75% of all; enterprises. A problem analysis on small and low maturitysoftware organizations revealed two; central reasons for not starting process improvement efforts: lack of resources and uncertainty; about process improvementeffort paybacks.; In the constructive part of the study a basic RE method, BaRE, was developed to provide an; easy to adopt way to introduce basic systematic RE practices in small and low maturity; organizations. Based on diffusion of innovations literature, thirteen desirable characteristics; were identified for the solution and the method was implemented in five key components:; requirements document template, requirements development practices, requirements; management practices, tool support for requirements management, and training.; The empirical evaluation of the BaRE method was conducted in three industrial case studies. In; this evaluation, two companies established a completely new RE infrastructure following the; suggested practices while the third company conducted continued requirements document; template development based on the provided template and used it extensively in practice. The; real benefits of the adoption of the method were visible in the companies in four to six months; from the start of the evaluation project, and the two small companies in the project completed; their improvement efforts with an input equal to about one person month. The collected dataon; the case studies indicates that the companies implemented new practices with little adaptations; and little effort. Thus it can be concluded that the constructed BaRE method is indeed easy to; adopt and it can help introduce basic systematic RE practices in small organizations.

The role of tributary relative timing and sequencing in controlling large floods

Hydrograph convolution is a product of tributary inputs from across the watershed. The time-space distribution of precipitation, the biophysical processes that control the conversion of precipitation to runoff and channel flow conveyance processes, are heterogeneous and different areas respond to rainfall in different ways. We take a subwatershed approach to this and account for tributary flow magnitude, relative timing, and sequencing. We hypothesize that as the scale of the watershed increases so we may start to see systematic differences in subwatershed hydrological response. We test this hypothesis for a large flood (T >100 years) in a large watershed in northern England. We undertake a sensitivity analysis of the effects of changing subwatershed hydrological response using a hydraulic model. Delaying upstream tributary peak flow timing to make them asynchronous from downstream subwatersheds reduced flood magnitude. However, significant hydrograph adjustment in any one subwatershed was needed for meaningful reductions in stage downstream, although smaller adjustments in multiple tributaries resulted in comparable impacts. For larger hydrograph adjustments, the effect of changing the timing of two tributaries together was lower than the effect of changing each one separately. For smaller adjustments synergy between two subwatersheds meant the effect of changing them together could be greater than the sum of the parts. Thus, this work shows that while the effects of modifying biophysical catchment properties diminishes with scale due to dilution effects, their impact on relative timing of tributaries may, if applied in the right locations, be an important element of flood management.