Pasture characteristics of Italian ryegrass and milk production under different management strategies

The objective of this work was to assess the effects of the sward structure of Italian ryegrass (Lolium multiflorum), during the first grazing cycle, on its morphological and bromatological characteristics throughout the growing season, and on the performance of dairy cows. The treatments consisted of two structures obtained as a function of canopy-light interception: high-light interception (HLI) and low-light interception (LLI), with different pre-grazing heights in the first grazing cycle. Pasture was managed under rotational grazing with a herbage allowance not below 30 kg dry matter (DM) per cow per day. Three grazing cycles, with a grazing interval of 30 days, were evaluated. Pre-grazing herbage mass was greater (2,240 vs. 1,656 kg ha-1 DM), but the proportion of leaf blades was smaller (0.35 vs. 0.43) for HLI swards. Neutral detergent fiber (NDF) content and organic matter digestibility (OMD) were similar between treatments in the first grazing cycle, but in the second and third ones NDF was greater, and OMD lower, for the HLI swards. Milk yields were greater for cows grazing LLI swards (19.4 vs. 21.1 kg per day). Initial grazing with 90% of light interception promotes greater nutritional value in the subsequent cycles.

Studies toward new anti-cancer strategies based on alpha-mannosidase inhibition.

Changes in the glycosylation pattern of cellular glycoproteins constitute a hallmark in human cancer and influence tumor progression, suggesting that inhibitors of selected glycosidases may control cancer progression. Following the studies on swainsonine, a natural inhibitor of Golgi alpha-mannosidase II, which highlighted the inhibition of cellular mannosidases as a potential innovative approach for the treatment of cancer, several dihydroxylated pyrrolidines and analogues were developed as new potent inhibitors of alpha-mannosidases II able to induce antiproliferative effects in human cancer cells.

Feeding strategies and energy to protein ratio on tambaqui performance and physiology

The objective of this work was to evaluate the effect of feed deprivation and refeeding with diets containing different energy to protein ratios (E/P) on the performance and physiology of juvenile tambaqui (Colossoma macropomum). A 4x2 factorial arrangement with three replicates was used, with four E/P ratios (11.5, 10.5, 9.5, and 8.5 kcal g-1 digestible energy per protein) and two feeding regimens (with and without deprivation), during 60 days. Fish from the food-deprived group were fasted for 14 days and refed from the fifteenth to the sixtieth day, whereas the remaining fish were fed for 60 days. At the end of the experimental period, weight of fish subjected to food deprivation was lower than that of those continuously fed; however, this condition did not influence the physiological parameters analyzed. Tambaqui fed 11.5 kcal g-1 achieved lower final weight than those fed with the other diets, in both regimens. Among the physiological parameters, only plasma protein presented significant increase in fish fed 8.5 kcal g-1, in both feeding regimens, probably due to the higher dietary protein concentration. These results indicate that fish show a partial compensatory growth, and that 10.5 kcal g-1 can be recommended for the diet of juvenile tambaqui.

Stocking densities and feeding strategies in shrimp and tilapia polyculture in tanks

The objective of this work was to evaluate the performance of Pacific marine shrimp (Litopenaeus vannamei) and tilapia (Oreochromis niloticus), in a polyculture in tanks subjected to different stocking densities and feeding strategies, in comparison with monoculture. Two experiments were performed, at the same time, in a completely randomized design with three treatments and four replicates each. Treatments for experiment I were: monoculture with 10 shrimp per m² (10S:0T); polyculture with 10 shrimp and 0.5 tilapia per m² (10S:0.5T); and polyculture with 10 shrimp and 1 tilapia per m² (10S:1T). Shrimp was the main crop, and feed was provided based on shrimp biomass. Treatments for experiment II were: monoculture with 2 tilapia per m² (2T:0S); polyculture with 2 tilapia and 2.5 shrimp per m² (2T:2.5S); and polyculture with 2 tilapia and 5 shrimp per m² (2T:5S). Tilapia was the main crop, and feed was provided based on fish requirements. In the experiment I, tilapia introduction to shrimp culture resulted in lower shrimp growth and poor feed conversion rate. In experiment II, shrimp introduction to tilapia culture did not interfere with fish performance. Polyculture is more efficient with the combination of 2 tilapia and 2.5 or 5 shrimp per m² and feed based on fish requirements.

Investigating the relationship between pollination strategies and the size-advantage model in zoophilous plants using the reproductive biology of Arum cylindraceum and other European Arum species as case studies

The size-advantage model (SAM) explains the temporal variation of energetic investment on reproductive structures (i.e. male and female gametes and reproductive organs) in long-lived hermaphroditic plants and animals. It proposes that an increase in the resources available to an organism induces a higher relative investment on the most energetically costly sexual structures. In plants, pollination interactions are known to play an important role in the evolution of floral features. Because the SAM directly concerns flower characters, pollinators are expected to have a strong influence on the application of the model. This hypothesis, however, has never been tested. Here, we investigate whether the identity and diversity of pollinators can be used as a proxy to predict the application of the SAM in exclusive zoophilous plants. We present a new approach to unravel the dynamics of the model and test it on several widespread Arum (Araceae) species. By identifying the species composition, abundance and spatial variation of arthropods trapped in inflorescences, we show that some species (i.e. A. cylindraceum and A. italicum) display a generalist reproductive strategy, relying on the exploitation of a low number of dipterans, in contrast to the pattern seen in the specialist A. maculatum (pollinated specifically by two fly species only). Based on the model presented here, the application of the SAM is predicted for the first two and not expected in the latter species, those predictions being further confirmed by allometric measures. We here demonstrate that while an increase in the female zone occurs in larger inflorescences of generalist species, this does not happen in species demonstrating specific pollinators. This is the first time that this theory is both proposed and empirically tested in zoophilous plants. Its overall biological importance is discussed through its application in other non-Arum systems.

Targeting Toll-Like Receptors: Promising Therapeutic Strategies for the Management of Sepsis-Associated Pathology and Infectious Diseases.

Toll-like receptors (TLRs) are pattern recognition receptors playing a fundamental role in sensing microbial invasion and initiating innate and adaptive immune responses. TLRs are also triggered by danger signals released by injured or stressed cells during sepsis. Here we focus on studies developing TLR agonists and antagonists for the treatment of infectious diseases and sepsis. Positioned at the cell surface, TLR4 is essential for sensing lipopolysaccharide of Gram-negative bacteria, TLR2 is involved in the recognition of a large panel of microbial ligands, while TLR5 recognizes flagellin. Endosomal TLR3, TLR7, TLR8, TLR9 are specialized in the sensing of nucleic acids produced notably during viral infections. TLR4 and TLR2 are favorite targets for developing anti-sepsis drugs, and antagonistic compounds have shown efficient protection from septic shock in pre-clinical models. Results from clinical trials evaluating anti-TLR4 and anti-TLR2 approaches are presented, discussing the challenges of study design in sepsis and future exploitation of these agents in infectious diseases. We also report results from studies suggesting that the TLR5 agonist flagellin may protect from infections of the gastrointestinal tract and that agonists of endosomal TLRs are very promising for treating chronic viral infections. Altogether, TLR-targeted therapies have a strong potential for prevention and intervention in infectious diseases, notably sepsis.

Strategies and tools for preventing neurotoxicity: to test, to predict and how to do it

A change in paradigm is needed in the prevention of toxic effects on the nervous system, moving from its present reliance solely on data from animal testing to a prediction model mostly based on in vitro toxicity testing and in silico modeling. According to the report published by the National Research Council (NRC) of the US National Academies of Science, high-throughput in vitro tests will provide evidence for alterations in"toxicity pathways" as the best possible method of large scale toxicity prediction. The challenges to implement this proposal are enormous, and provide much room for debate. While many efforts address the technical aspects of implementing the vision, many questions around it need also to be addressed. Is the overall strategy the only one to be pursued? How can we move from current to future paradigms? Will we ever be able to reliably model for chronic and developmental neurotoxicity in vitro? This paper summarizes four presentations from a symposium held at the International Neurotoxicology Conference held in Xi"an, China, in June 2011. A. Li reviewed the current guidelines for neurotoxicity and developmental neurotoxicity testing, and discussed the major challenges existing to realize the NCR vision for toxicity testing. J. Llorens reviewed the biology of mammalian toxic avoidance in view of present knowledge on the physiology and molecular biology of the chemical senses, taste and smell. This background information supports the hypothesis that relating in vivo toxicity to chemical epitope descriptors that mimic the chemical encoding performed by the olfactory system may provide a way to the long term future of complete in silico toxicity prediction. S. Ceccatelli reviewed the implementation of rodent and human neural stem cells (NSCs) as models for in vitro toxicity testing that measures parameters such as cell proliferation, differentiation and migration. These appear to be sensitive endpoints that can identify substances with developmental neurotoxic potential. C. Sun ol reviewed the use of primary neuronal cultures in testing for neurotoxicity of environmental pollutants, including the study of the effects of persistent exposures and/or in differentiating cells, which allow recording of effects that can be extrapolated to human developmental neurotoxicity.

Growth strategies of international companies in the emerging markets of South-East Europe

Työn tarkoituksena oli tutkia niitä tekijöitä jotka ovat vaikuttaneet kansainvälisten yritysten myynnin kasvuun Romaniassa, Bulgariassa, Serbiassa ja Sloveniassa. Tutkimusta varten haastateltiin neljää kansainvälisen yrityksen edustajaa sekä 16 kansainvälisen kaupan ammattilaista. Työn akateemisena viitekehyksenä käytettiin keskeisiä kansainvälisen liiketoiminnan teorioita sekä myynnin strategista viitekehystä. Johtopäätöksenä katsotaan, että menestyvillä yrityksillä on selvä kansainvälistymis-strategia, kansainvälinen organisaatio, konsultoiva myyntityyli ja resursseja investoida koulutukseen. Tarkastelun alla olevista maista etenkin Romaniasta ja Bulgarista löytyy liiketoiminta potentiaalia. Tutkimuksen johtopäätökset perustuvat laadullisiin ja määrällisiin tutkimusmenetelmiin ja ne on tarkoitettu palvemaan Tikkurila Oy:tä. Tutkimustuloksia on myös mahdollista soveltaa laajemmin samanlaisessa tutkimusympäristössä, kunhan tutkittavan liiketoimintaympäristön erityispiirteet ovat otetttu huomioon

Successful business strategies during periods of crisis

Treball Final de Carrera ( TFC ) consistent en l'anàlisi de diferents tipus d'estratègies que les empreses poden aplicar centrant-se en les idees de Michael Porter i el desenvolupament d'aquestes idees per part de diferents professionals. El TFC està dividit en dos blocs, un de teòric i un de pràctic. El primer bloc consisteix en l'anàlisi dels diferents tipus d'estratègies derivades de les idees de Michael Porter. En aquest primer bloc, hem analitzat com a través del model de les cinc forces, Porter va arribar a les estratègies genèriques. Després hem analitzat les tres estratègies genèriques conjuntament amb l'estratègia híbrida i amb l'Estratègia de l'Oceà Blau. El segon bloc està format per diversos casos pràctics d'empreses que han aconseguit l'èxit durant l'actual període de crisi en els diferents sectors de l'economia. Aquestes empreses són Yoigo com a exemple de baix cost , Starbucks com implementació d'una estratègia de diferenciació i Ryan Air exemplificant una estratègia de segmentació enfocada als baixos costos. Finalment, hem analitzat a Toyota degut a la seva estratègia híbrida i Graphenea com una companyia que implementa Estratègia de l'Oceà Blau. Totes aquestes companyies han aconseguit l'èxit durant l'actual període de crisi. El motiu és que aquestes empreses van escollir un tipus d'estratègia d'acord amb l'estructura de la indústria en la qual operen. No obstant això, la implementació d'aquestes estratègies no assegura resultats d'èxit. L'adequada aplicació d'aquestes estratègies suposa per a les empreses una demostració de que aconseguir l'èxit durant períodes de recessió econòmica és possible, vinculat a una bona gestió estratègica.

Comparaison de stratégies thérapeutiques dans la prise en charge de l'hypertension artérielle [Comparison of therapeutic strategies in the management of hypertension]

Guidelines for the treatment of hypertension recommend reducing blood pressure to below 140/90 mmHg. However, there is little to guide the clinician on which pharmacological strategy to pursue: monotherapy with stepped-care, sequential monotherapy, or the initial use of combination therapy. The STRATHE study was designed to clarify this issue by comparing the three strategies. A low-dose combination of perindopril/indapamide was significantly superior to either stepped-care or sequential monotherapy in terms of reducing systolic blood pressure and in the percentage of patients achieving normalisation without adverse effects. Pulse pressure showed a trend to greater reductions with the low-dose combination. Although there must be caution about extrapolating these results to other combinations, which may not have the same pharmacological properties, the STRATHE study has shown that initiating antihypertensive therapy with a low-dose combination has advantages over the two other classical therapeutic strategies.

The Effectiveness of Currency Hedging Strategies. Case: Imatra Boards Business Unit of Stora Enso Corp.

Tutkimus tarkastelee vaihtoehtoisia termiinisuojaustrategioita metsäteollisuuden alan tulosyksikössä. Jälkitestauksen tarkoituksena on arvioida vaihtoehtoisten strategioiden tuloksellisuutta suojata case-yrityksen kassavirtoja seuraavan kolmen arviointikriteerin avulla: yksittäisten vieraan valuutan määräisten kassavirtojen vaihtelu; koko vieraan valuutan määräisen kassavirran vaihtelu; suojausvoitot ja -tappiot. Tutkimuksen teoreettinen viitekehys tarkastelee yrityksen päätöksentekoa, valuuttariskien suojausprosessia sekä esittelee yrityksen vaihtoehtoisia suojausstrategioita. Tutkimuksen empiirinen aineisto pohjautuu case- yrityksen historiallisiin myyntilukuihin ja on kerätty yrityksen tietojärjestelmästä. Muu tutkimuksessa käytetty dataon kerätty eri tietokannoista. Tutkimuksen tulokset osoittavat, että suojaaminen vähentää kassavirtojen vaihtelua. Suojaamisen taloudelliset tulokset ovat kuitenkin erittäin riippuvaisia valitusta suojausstrategiasta, joka voi johtaa merkittäviin suojausvoittoihin, mutta yhtä hyvin myos merkittäviin tappioihin. Johdon näkemykset ja riskitoleranssi määrittelevät mitä strategiaa yrityksessä tullaan viime kädessä noudattamaan.

Magazine publishers and their online strategies

It seems as if magazine publishers have only haphazardly listed multiple goals for their websites, and have not carefully reflectedon how to achieve them. We present a framework for defining a magazine's onlinestrategy based on previous studies and on secondary data from the industry. We identify three steps in the strategy process. The first is to determine whether the magazine would actually benefit from online presence: although most magazines will never make money from their websites, a web presence may still be justified. The second step is to choose an optimal online strategy that matches the magazine's competitive strategy. Finally, we argue that magazine publishers should carefully consider to what extent they should allow their readers to be involvedin the web pages. This interactivity could be seen as a key factor in exploiting the unique nature of the Internet. It is our understanding that virtual communities could, at best, be a way of creating more value for a magazine's readers, advertisers and editors, alike. We formulate a typology of five different onlinebusiness concepts for magazines based on these three strategic steps.

Glutathione deficit in schizophrenia: strategies to increase glutathione levels in " in vitro " and clinical studies

Summary: Decrease in glutathione (GSH) levels was observed in cerebrospinal fluid, prefrontal cortex and post-mortem striatum of schizophrenia patients. Evidences suggest a defect in GSH synthesis at the levels of the rate-limiting synthesizing enzyme, glutamate cysteine ligase (GCL). Indeed, polymorphisms in the gene of the modifier subunit of GCL (GCLM) was shown to be associated with the disease in three different populations, GCLM gene expression is decreaséd in fibroblasts from patients and the increase in GCL activity induced by an oxidative stress is lower in patients' fibroblasts compared to controls. GSH being a major antioxydant and redox regulator, its presence is of high importance for protecting cells against oxidative stress. The aim of the present work was to use various substances to increase GSH levels by diverse strategies. Since the synthesizing enzyme GCL is defective, bypassing this enzyme was the first strategy we used. GSH ethyl ester (GSHEE), a membrane permeable analog of GSH, succeeded in replenishing GSH levels in cultured neurons and astrocytes previously depleted in GSH by L-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of GCL. GSHEE also abolished dopamine-induced decrease of NMDA-mediated calcium response observed in BSO-treated neurons. y-Glutamylcysteine ethyl ester (GCSE), a membrane permeable analog of the product of GCL, increased GSH levels only in astrocytes. The second strategy was to boost the defective enzyme GCL. While quercetin (flavonoid) could increase GSH levels only in astrocytes, curcumin (polyphenol) and tertbutylhydroquinone (quinone) were successful in both neurons and astrocytes, via an increase in the gene expression of the two subunits of GCL and, consequently, an increase in the activity of the enzyme. However, FK506, an immunosupressant, was unefficient. Treating astrocytes from GCLM KO mice showed that the modulatory subunit is necessary for the action of the substances. Finally, since cysteine is the limiting precursor in the synthesis of GSH, we hypothesized that we could increase GSH levels by providing more of this precursor. N-acetyl-cysteine (NAC), a cysteine donor, was administered to schizophrenia patients, using adouble-blind and cross-over protocol. NAC significantly improved the mismatch negativity (MMN), a component of the auditory evoked potentials, thought to reflect selective current flowing through open, unblocked NMDA channels. Considering that NMDA function is reduced when GSH levels are low, increasing these levels with NAC could improve NMDA function as reflected by the improvement in the generation of the MMN. Résumé: Les taux de glutathion (GSH) dans le liquide céphalo-rachidien, le cortex préfrontal ainsi que le striatum post-mortem de patients schizophrènes, sont diminués. L'enzyme limitante dans la synthèse du GSH, la glutamyl-cysteine ligase (GCL), est défectueuse. En effet, des polymorphismes dans le gène de la sous-unité modulatrice de GCL (GCLM) sont associés à la maladie, l'expression du gène GCLM est diminuée dans les fibroblastes de patients et, lors d'un stress oxidative, l'augmentation de l'activité de GCL est plus faible chez les patients que chez les contrôles. Le GSH étant un important antioxydant et régulateur du status redox, sa présence est primordiale afin de protéger les cellules contre les stress oxydatifs. Au cours du présent travail, une variété de substances ont été utilisées dans le but d'augmenter les taux de GSH. Passer outre l'enzyme de synthèse GCL qui est défectueuse fut la première stratégie utilisée. L'éthylester de GSH (GSHEE), un analogue du GSH qui pénètre la membrane cellulaire, a augmenté les taux de GSH dans des neurones et des astrocytes déficitaires en GSH dû au L-buthionine-(S,R)-sulfoximine (BSO), un inhibiteur du GCL. Dans ces neurones, le GSHEE a aussi aboli la diminution de la réponse NMDA, induite parla dopamine. L'éthyl-ester de y-glutamylcysteine (GCEE), un analogue du produit de la GCL qui pénètre la membrane cellulaire, a augmenté les taux de GSH seulement dans les astrocytes. La seconde stratégie était d'augmenter l'activité de l'enzyme GCL. Tandis que la quercétine (flavonoïde) n'a pu augmenter les taux de GSH que dans les astrocytes, la curcumin (polyphénol) et le tert-butylhydroquinone (quinone) furent efficaces dans les deux types de cellules, via une augmentation de l'expression des gènes des deux sous-unités de GCL et de l'activité de l'enzyme. Le FK506 (immunosupresseur) n' a démontré aucune efficacité. Traiter des astrocytes provenant de souris GCLM KO a permis d'observer que la sous-unité modulatoire est nécessaire à l'action des substances. Enfin, puisque la cysteine est le substrat limitant dans la synthèse du GSH, fournir plus de ce présurseur pourrait augmenter les taux de GSH. Nacétyl-cystéine (NAC), un donneur de cystéine, a été administrée à des schizophrènes, lors d'une étude en double-aveugle et cross-over. NAC a amélioré le mismatch negativity (MMN), un composant des potentials évoqués auditifs, qui reflète le courant circulant via les canaux NMDA. Puisque la fonctionnalité des R-NMDA est diminuée lorsque les taux de GSH sont bas, augmenter ces taux avec NAC pourrait améliorer la fonction des R-NMDA, réflété par une augmentation de l'amplitude du MMN.