79 research outputs found

    Mutual information for symmetric rank-one matrix estimation: A proof of the replica formula

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    Factorizing low-rank matrices has many applications in machine learning and statistics. For probabilistic models in the Bayes optimal setting, a general expression for the mutual information has been proposed using heuristic statistical physics computations, and proven in few specific cases. Here, we show how to rigorously prove the conjectured formula for the symmetric rank-one case. This allows to express the minimal mean-square-error and to characterize the detectability phase transitions in a large set of estimation problems ranging from community detection to sparse PCA. We also show that for a large set of parameters, an iterative algorithm called approximate message-passing is Bayes optimal. There exists, however, a gap between what currently known polynomial algorithms can do and what is expected information theoretically. Additionally, the proof technique has an interest of its own and exploits three essential ingredients: the interpolation method introduced in statistical physics by Guerra, the analysis of the approximate message-passing algorithm and the theory of spatial coupling and threshold saturation in coding. Our approach is generic and applicable to other open problems in statistical estimation where heuristic statistical physics predictions are available

    Optimisation et simulation pour la gestion de disponibilite sous comportement d’achat

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    RÉSUMÉ: Nous nous intĂ©ressons dans ce doctorat Ă  l’optimisation de la disponibilitĂ© de l’offre au cours d’une pĂ©riode de rĂ©servation pendant laquelle des ressources pĂ©rissables sont vendues. Cette problĂ©matique appartient au domaine de la gestion de revenu plus communĂ©ment dĂ©signĂ© par le terme anglais de revenue management. Afin d’illustrer notre propos, considĂ©rons le siĂšge d’un train effectuant un trajet entre deux villes Ă  une certaine date et heure. Ce siĂšge est une ressource pĂ©rissable, car il ne peut pas ĂȘtre proposĂ© une fois le train parti. Cette ressource doit donc ĂȘtre vendue avant son terme durant une pĂ©riode de rĂ©servation. Des clients arrivent pendant cette pĂ©riode pour Ă©ventuellement rĂ©server cette ressource en achetant un des produits offerts. Les produits sont dĂ©finis Ă  l’avance par leur tarif et leurs conditions. Ces derniĂšres portent sur l’annulation, l’échange, l’accĂšs au wifi ou une offre de repas par exemple. Chaque client choisira Ă©ventuellement d’acheter l’un de ces produits en fonction d’un comportement d’achat qui lui est propre. Ce doctorat se rĂ©sume Ă  dĂ©terminer quels produits offrir Ă  chaque arrivĂ©e de client afin de maximiser le revenu gĂ©nĂ©rĂ© par l’ensemble des ventes rĂ©alisĂ©es au cours de la pĂ©riode de rĂ©servation. Pour se faire, les ressources et produits sont fixĂ©s ainsi que la demande qui est connue au moyen d’une prĂ©vision. L’optimisation des ressources et produits ainsi que la prĂ©vision de la demande ne font pas l’objet de ce doctorat et sont d’ailleurs presque toujours traitĂ©es sĂ©parĂ©ment dans le domaine de gestion de revenu. Le dilemme suivant est soulevĂ©. D’un cĂŽtĂ© en acceptant une requĂȘte, nous assurons un revenu, mais nous diminuons la capacitĂ© disponible pour des requĂȘtes futures Ă©ventuellement de meilleur revenu. Il peut donc y avoir de la dilution. D’un autre cĂŽtĂ©, en refusant une requĂȘte, nous rĂ©servons de la capacitĂ© pour d’éventuelles requĂȘtes futures Ă  meilleur revenu tout en perdant la requĂȘte prĂ©sente Ă  revenu sĂ»r. Il peut donc y avoir du gaspillage. Deux grandes Ă©volutions ont successivement changĂ© la modĂ©lisation de ce problĂšme et ont amĂ©liorĂ© la robustesse des solutions tout en le complexifiant. La premiĂšre a pris en compte les ressources dans leur ensemble plutĂŽt qu’individuellement. La deuxiĂšme a intĂ©grĂ© le comportement d’achat de clients lĂ  oĂč auparavant la demande Ă©tait considĂ©rĂ©e de façon indĂ©pendante par produit. Aujourd’hui, une formulation exacte intĂ©grant ces deux aspects existe, mais est trop rapidement insoluble. Des approximations ont donc Ă©tĂ© proposĂ©es. L’objectif est de retourner rapidement une politique de disponibilitĂ© gĂ©nĂ©rant le meilleur revenu espĂ©rĂ© une fois simuler. Dans un premier temps, nous prĂ©sentons une approximation pour un comportement d’achat non paramĂ©trique. Ce type de demande est abondamment utilisĂ© en pratique et modĂ©lise mieux les substitutions de produits que beaucoup de modĂšles paramĂ©triques. Il jouit aussi de plus en plus de recherches sur son estimation, mais de peu de travaux en gestion de la disponibilitĂ©. Nous introduisons alors un des trois concepts importants de ce doctorat qui est l’utilisation de temps de fermeture par produit comme politique de disponibilitĂ©. Cette derniĂšre s’adapte pleinement Ă  la logique d’achat non paramĂ©trique contrairement aux modĂšles existants. Nous arrivons Ă  un modĂšle Ă  nombres entiers dont les variables binaires rendent compte d’une hiĂ©rarchie de produit qui a un rĂ©el sens pratique. Cela nous permet de proposer de bonnes solutions initiales trĂšs facilement. La politique par temps de fermeture empĂȘche naturellement la rĂ©ouverture Ă  la vente de produits au cours de la pĂ©riode de rĂ©servation. Il faut savoir que cet aspect est souvent dĂ©sirĂ© en pratique et nĂ©cessite la complexification des approches existantes contrairement Ă  la nĂŽtre. Dans le cas de non-rĂ©ouverture, nous prouvons que notre approximation est une borne supĂ©rieure pour la formulation exacte et qu’elle est asymptotiquement optimale. Nous pouvons utiliser la politique retournĂ©e par notre approximation comme solution initiale de n’importe quelle approximation Ă  rĂ©ouverture. Des rĂ©sultats numĂ©riques sur des instances de petites Ă  grandes tailles montrent que notre approximation, par rapport aux approches existantes, retourne beaucoup plus rapidement une politique de disponibilitĂ© gĂ©nĂ©rant un revenu espĂ©rĂ© lĂ©gĂšrement supĂ©rieur. Ils mettent aussi en Ă©vidence l’accĂ©lĂ©ration des approximations existantes lorsque notre approche est utilisĂ©e comme solution de dĂ©part. Dans un second temps, poussĂ©s par les rĂ©sultats prĂ©cĂ©dents, nous cherchons Ă  gĂ©nĂ©raliser l’approche prĂ©cĂ©dente Ă  tout comportement d’achat. Nous reprĂ©sentons d’abord toute demande sous la forme de chemins d’achats formant ainsi un arbre de demande. Cet arbre de demande est le second concept important de ce doctorat. Nous utilisons le fait que chaque chemin d’achat est non paramĂ©trique pour construire une nouvelle approximation acceptant n’importe quel comportement d’achat. Notre nouvelle approximation hĂ©rite de la politique de disponibilitĂ© par temps de fermeture et donc de la non rĂ©ouverture. Nous utilisons alors la mĂȘme linĂ©arisation et nous Ă©tendons les rĂ©sultats thĂ©oriques prĂ©cĂ©dents. Les modĂšles paramĂ©triques retournent un arbre de demande immense qui rend notre approximation insoluble. Pour pallier cela, nous prĂ©sentons une mĂ©thode de rĂ©solution itĂ©rative basĂ©e sur une construction progressive de l’arbre de demande par un ajout successif de chemins d’achats. Nous proposons plusieurs heuristiques pour dĂ©terminer quel chemin d’achat ajouter. Chaque ajout raffine la modĂ©lisation du comportement d’achat. Nous menons ensuite des expĂ©riences numĂ©riques sur des instances Ă  comportement d’achat paramĂ©trique de petite Ă  grande taille. Les rĂ©sultats montrent des rĂ©sultats similaires Ă  ceux pour le non paramĂ©trique et la mĂ©thode itĂ©rative de rĂ©solution converge vers une bonne solution beaucoup plus rapidement que les autres approches. Dans un dernier temps, nous nous penchons sur la simulation pour la gestion de disponibilitĂ©. Nous proposons un nouvel estimateur Ă  arrivĂ©es fluides pour le calcul du revenu espĂ©rĂ©. Cette modĂ©lisation par arrivĂ©es fluides est le troisiĂšme concept important de ce doctorat. Notre modĂšle agrĂšge alors les diffĂ©rentes arrivĂ©es par segment, et ce pour toute la pĂ©riode de rĂ©servation. Il ne subit donc pas l’alĂ©atoire d’un ordre d’arrivĂ©es. Il nĂ©cessite alors une seule Ă©valuation et est invariant alors que l’estimateur traditionnel Ă  arrivĂ©es discrĂštes ne peut rĂ©duire la variance et donc augmenter la prĂ©cision qu’en augmentant le nombre d’évaluations. En contrepartie, nous montrons que notre estimateur prĂ©sente un biais, contrairement Ă  l’estimateur traditionnel, pouvant ĂȘtre arbitrairement grand mĂȘme si cela reste minime en pratique. Nous expĂ©rimentons alors des mĂ©thodes d’optimisation basĂ©es sur la simulation afin de rĂ©soudre le problĂšme de contrĂŽle de la disponibilitĂ©. Nous concluons rapidement que la bonne convergence de ces mĂ©thodes dĂ©pend largement du point de dĂ©part fourni par un modĂšle en programmation mathĂ©matique. Cette conclusion a Ă©tĂ© un moteur pour le dĂ©veloppement des approximations prĂ©cĂ©dentes. D’ailleurs, nous montrons que notre estimateur est Ă©quivalent Ă  la plupart des approximations pour le contrĂŽle de la disponibilitĂ©. En consĂ©quence, nous Ă©voquons quelques possibilitĂ©s de notre estimateur pour appuyer l’optimisation. Les rĂ©sultats numĂ©riques sur des instances de grandes tailles tĂ©moignent de la nette supĂ©rioritĂ© de notre estimateur en termes de temps de calcul. Nous constatons aussi peu de biais pour toutes les instances Ă©tudiĂ©es.----------ABSTRACT: This thesis focuses on the availability policy problem when selling perishable resources during a reservation period. This problem belongs to the revenue management topic. For example, a seat in a train between two cities at 9am on may 3rd 2018 is a perishable resource because it cannot be sold after the train departure. We must sell this resource through a reservation period before it expires and during which customers arrive to eventually buy a product. Many products can exist and are defined in advance by their terms and rates. For example, tickets for this seat can offer cancellation or exchange. A Meal or a wi-fi access can even be proposed at another cost. Each customer will then choose a product or not according to its own choice behaviour. This thesis aims to determinate which products to offer at each client arrival in order to maximize the income generated by the sales during the reservation period. Products and resources are fixed and demand is known. The products and resources optimization as well as the forecasting are not tackled in this thesis. Besides, they are almost always treated separately in revenue management. The following dilemma is raised. Accepting a request, provides an income, but removes one capacity for a future and potential higher request. This is called spillage. Whereas denying a request, protects a potential higher income but loses an immediate and safe income. This is named spoilage. Two major developments successively changed the model of this problem and improved the robustness of solutions while increasing the complexity. The first was to consider resources together rather than individually. The second is the integration of the customer choice behaviour rather than an independent demand by product. Today an exact formulation integrates both aspects but is too rapidly intractable. Approximations have therefore been proposed. The challenge is to quickly return an availability policy generating the best expected revenue when simulated. In a first part, we present an approximation for a non-parametric choice behaviour. This type of demand is widely used in practice and better accounts for products substitutions than many parametric models. It also benefits from recent research on its estimation and is rarely investigated for the availability policy problem. This approximation benefits from one of the three major concepts of this thesis which is an availability policy by closing times per product. This policy fully adapts to the non-parametric buying logic contrarily to existing models. The model is mixed integer with variables that account for a product hierarchy having a practical meaning. This allows us to easily offer good initial solutions in order to accelerate the resolution of our approximation. The closing time policy naturally prevents the reopening of products during the booking period. This aspect is often desired in practice. To force no reopening, existing approximations must be adapted and are thus more complex to solve. In the case of no reopening, we prove that our approximation is an upper bound for the exact formulation and that it is asymptotically optimal. We can use the policy returned by our approximation as an initial solution of any reopening approximation. Numerical results on small to large instances show that our approximation, compared to existing approaches, returns much faster an availability policy generating slightly higher expected revenue. They also highlight the acceleration of existing approximations when our approach is used as a starting solution. In a second part, driven by the previous results, we seek to generalize the previous approach to any choice behavior. We first represent any demand in the form of buying paths forming a demand tree. This demand tree is the second important concept of this thesis. Each buying path is non-parametric so that we extend previous results by introducing new approximation accepting any choice behavior. It inherits the closing time availability policy and by consequence the no reopening. We then use the same linearization and extend the previous theoretical results. Parametric choice models return huge and intractable demand tree. To overcome this, we present an iterative resolution method based on a progressive construction of the demand tree by a successive addition of buying paths. We propose several heuristics to determine which buying path to add. We then conduct numerical experiments on small to large instances with parametric choice behaviour. The results are similar to those for nonparametric and the iterative method of resolution converges much faster to a good solution than existing approximations. In the last part, we focus on simulation for the availability policy problem. We propose a new fluid arrivals estimator to determinate the expected revenue. This fluid arrivals aspect is the third major concept of this thesis. It aggregates the different arrivals by segment for the entire booking period. It thus does not suffer from the randomness of ordered arrivals. Consequently, it requires only one evaluation and is invariant whereas the traditional discrete arrivals estimator can only reduce the variance by increasing the number of evaluations. However, we show that our estimator has a bias, unlike the traditional estimator, which can be arbitrarily large even if remains minimal in practice. We then experiment optimization-based simulation methods to solve the availability policy problem. We quickly conclude that the good convergence of these methods highly depends on the starting point provided by a mathematical programming model. This conclusion has been a motivation for the development of the previous approximations. Moreover, we show that our estimator is equivalent to most of these approximations. As a result, we discuss some applications for our estimator to support optimization. The numerical results on large-scale instances highlight the superiority of our estimator in terms of computation time. We also found only a little bias for all instances studied

    Optimisation de la stratégie et du dimensionnement des systÚmes hybrides éoliens, diesel, batterie pour sites isolés

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    RÉSUMÉ : Imaginons que nous venons de dĂ©couvrir une ressource exploitable dans le nord du QuĂ©bec (Canada) Ă  environ 1000 km de tout rĂ©seau d'approvisionnement en Ă©lectricitĂ©. Nous allons rapidement nous demander comment fournir l'Ă©lectricitĂ© nĂ©cessaire Ă  son exploitation. La construction et l'entretien d'une ligne de transport jusqu'au rĂ©seau le plus proche rendrait le projet non rentable. La seule solution envisageable est de produire l'Ă©lectricitĂ© de maniĂšre locale et autonome. Ce besoin concerne de nombreux sites isolĂ©s dans le monde parmi lesquels des villages autochtones, stations de communication, sites d'extraction de matiĂšre premiĂšre ou encore camps militaires . Les experts prĂ©voient ainsi un marchĂ© de 10 milliards de dollars vers 2020 pour l'approvisionnement en Ă©nergie de ces sites isolĂ©s. Les sites isolĂ©s sont traditionnellement alimentĂ©s en Ă©lectricitĂ© par des gĂ©nĂ©ratrices diesel trĂšs coĂ»teuses en carburant et de par son acheminement. En plein essor et poussĂ© par une volontĂ© d'Ă©nergie renouvelable, l'Ă©olien a commencĂ© Ă  ĂȘtre implantĂ© dans les annĂ©es 1990. Quelques annĂ©es de mise au point ont Ă©tĂ© nĂ©cessaires pour que cette technologie soit maintenant parfaitement implantĂ©e dans quelques sites isolĂ©s. Avec les progrĂšs effectuĂ©s, le stockage par batteries devient une solution insistante pour palier Ă  l'intermittence de l'Ă©olien et donc rĂ©duire encore plus l'utilisation des gĂ©nĂ©ratrices diesel. De nombreux modĂšles de systĂšmes hybrides diesel - Ă©olien - batterie ont ainsi Ă©tĂ© dĂ©veloppĂ©s pour dĂ©terminer leur potentiel et leur faisabilitĂ©. A cause de l'hybridation, ces modĂšles exigent une stratĂ©gie de contrĂŽle pour dĂ©terminer Ă  chaque instant la rĂ©partition de la fourniture d'Ă©lectricitĂ© entre les trois Ă©lĂ©ments. Le dĂ©fi de l'optimisation des sites isolĂ©s est de de trouver simultanĂ©ment le dimensionnement et la stratĂ©gie de contrĂŽle. Dans notre approche nommĂ©e OGESO pour Off-Grid Electricity Supply Optimization, nous modĂ©lisons le systĂšme hybride Ă  l'aide de la programmation linĂ©aire en nombres entiers (PLNE). La rĂ©solution de ce modĂšle sur des donnĂ©es horaires dĂ©terministes d'un an de demande et de vent nous permet d'obtenir le dimensionnement et la rĂ©partition optimale pour cette annĂ©e de donnĂ©es sans avoir Ă  fixer de stratĂ©gie. Nous appliquons ensuite l'extraction de donnĂ©es (data mining) Ă  cette rĂ©partition optimale d'un an afin d'en extraire une stratĂ©gie appropriĂ©e. Notre approche couplant PLNE et data mining est nouvelle et permet de lier l'optimisation de la stratĂ©gie Ă  celle du dimensionnement. GrĂące Ă  cette stratĂ©gie adaptĂ©e, nous exploitons mieux le potentiel des systĂšmes hybrides et nos systĂšmes sont mieux optimisĂ©s que par les logiciels usuels de simulation comme HOMER.----------ABSTRACT : Imagine you have just discovered a workable resource in the north of QuĂ©bec (Canada), which is 1000 km away from any electrical grid. You will rapidly wonder how to supply electricity to exploit it. The high extension cost of the grid leaves only one alternative: to produce the energy locally and autonomously. As mining increases in remote areas in wide countries such as India or China, the number of such isolated sites will rise. Experts predict an energy market of \$10B for this type of site by 2020. Traditionally electricity was guaranteed by diesel generation. This technology is easy to implement but is also very expensive because of fuel price and transportation. Moreover it is in opposition to the objective of increased use of green energy. The use of wind turbines in remote areas in order to reduce fuel consumption by wind was proposed in 1990s. After some years of adjustment, this technology was mature and is now widely used in Alaska off-grid sites. Batteries have recently known great progress and are a solution against wind intermittency. Its may further reduce the use of diesel generators. Thus a lot of models composed of wind, diesel and batteries have been developed to determine their potential and feasibility. These hybrid systems can work only because of an operation strategy. This strategy is established by deciders and states the rules of the system: when and how dispatching energy from the 3 elements. The challenge in hybrid systems optimization is to find both optimal sizing and optimal strategy, which are linked and influence each other. Additionally the optimization is made through stochastic wind and load data’s. We use Mixed Integer Programming (MIP) in order to eliminate the need to choice a strategy. Because we give what the wind and load would be for a whole year, MILP find optimal sizing and optimal dispatch for this year. It is not a strategy but what we would have done at each hour in the year to have the perfect dispatch. One year optimal dispatch represents the reference from which data mining will be applied to get an appropriate strategy. Our approach of MIP and data mining coupling which we call OGESO for Off-Grid Optimization Electricity Supply Optimization is new and make hybrid system used more effectively with this more accurate strategy. Thus system works cheaper and project costs are better than simulation softwares usually used in hybrid system design like HOMER

    Product-Closing Approximation for Ranking-based Choice Network Revenue Management

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    Most recent research in network revenue management incorporates choice behavior that models the customers' buying logic. These models are consequently more complex to solve, but they return a more robust policy that usually generates better expected revenue than an independent-demand model. Choice network revenue management has an exact dynamic programming formulation that rapidly becomes intractable. Approximations have been developed, and many of them are based on the multinomial logit demand model. However, this parametric model has the property known as the independence of irrelevant alternatives and is often replaced in practice by a nonparametric model. We propose a new approximation called the product closing program that is specifically designed for a ranking-based choice model representing a nonparametric demand. Numerical experiments show that our approach quickly returns expected revenues that are slightly better than those of other approximations, especially for large instances. Our approximation can also supply a good initial solution for other approaches

    Loss of RNase J leads to multi-drug tolerance and accumulation of highly structured mRNA fragments in Mycobacterium tuberculosis

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    Despite the existence of well-characterized, canonical mutations that confer high-level drug resistance to Mycobacterium tuberculosis (Mtb), there is evidence that drug resistance mechanisms are more complex than simple acquisition of such mutations. Recent studies have shown that Mtb can acquire non-canonical resistance-associated mutations that confer survival advantages in the presence of certain drugs, likely acting as stepping-stones for acquisition of high-level resistance. Rv2752c/rnj, encoding RNase J, is disproportionately mutated in drug-resistant clinical Mtb isolates. Here we show that deletion of rnj confers increased tolerance to lethal concentrations of several drugs. RNAseq revealed that RNase J affects expression of a subset of genes enriched for PE/PPE genes and stable RNAs and is key for proper 23S rRNA maturation. Gene expression differences implicated two sRNAs and ppe50-ppe51 as important contributors to the drug tolerance phenotype. In addition, we found that in the absence of RNase J, many short RNA fragments accumulate because they are degraded at slower rates. We show that the accumulated transcript fragments are targets of RNase J and are characterized by strong secondary structure and high G+C content, indicating that RNase J has a rate-limiting role in degradation of highly structured RNAs. Taken together, our results demonstrate that RNase J indirectly affects drug tolerance, as well as reveal the endogenous roles of RNase J in mycobacterial RNA metabolism.Fil: Martini, MarĂ­a Carla. Worcester Polytechnic Institute; Estados Unidos. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas; ArgentinaFil: Hicks, Nathan D.. Harvard University. Harvard School of Public Health; Estados UnidosFil: Xiao, Junpei. Worcester Polytechnic Institute; Estados UnidosFil: Alonso, Maria Natalia. Worcester Polytechnic Institute; Estados Unidos. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas; ArgentinaFil: Barbier, Thibault. Harvard University. Harvard School of Public Health; Estados UnidosFil: Sixsmith, Jaimie. Harvard University. Harvard School of Public Health; Estados UnidosFil: Fortune, Sarah M.. Harvard University. Harvard School of Public Health; Estados UnidosFil: Shell, Scarlet S.. Worcester Polytechnic Institute; Estados Unido

    Glucose Oxidation to Pyruvate Is Not Essential for Brucella suis Biovar 5 Virulence in the Mouse Model

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    Brucella species cause brucellosis, a worldwide extended zoonosis. The brucellae are related to free-living and plant-associated alpha 2-Proteobacteria and, since they multiply within host cells, their metabolism probably reflects this adaptation. To investigate this, we used the rodent-associated Brucella suis biovar 5, which in contrast to the ruminant-associated Brucella abortus and Brucella melitensis and other B. suis biovars, is fast-growing and conserves the ancestral Entner-Doudoroff pathway (EDP) present in the plant-associated relatives. We constructed mutants in Edd (glucose-6-phosphate dehydratase; first EDP step), PpdK (pyruvate phosphate dikinase; phosphoenolpyruvate pyruvate), and Pyk (pyruvate kinase; phosphoenolpyruvate -> pyruvate). In a chemically defined medium with glucose as the only C source, the Edd mutant showed reduced growth rates and the triple Edd-PpdK-Pyk mutant did not grow. Moreover, the triple mutant was also unable to grow on ribose or xylose. Therefore, B. suis biovar 5 sugar catabolism proceeds through both the Pentose Phosphate shunt and EDP, and EDP absence and exclusive use of the shunt could explain at least in part the comparatively reduced growth rates of B. melitensis and B. abortus. The triple Edd-PpdK-Pyk mutant was not attenuated in mice. Thus, although an anabolic use is likely, this suggests that hexose/pentose catabolism to pyruvate is not essential for B. suis biovar 5 multiplication within host cells, a hypothesis consistent with the lack of classical glycolysis in all Brucella species and of EDP in B. melitensis and B. abortus. These results and those of previous works suggest that within cells, the brucellae use mostly 3 and 4 C substrates fed into anaplerotic pathways and only a limited supply of 5 and 6 C sugars, thus favoring the EDP loss observed in some species

    The Hepatokine TSK does not affect brown fat thermogenic capacity, body weight gain, and glucose homeostasis

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    Objectives Hepatokines are proteins secreted by the liver that impact the functions of the liver and various tissues through autocrine, paracrine, and endocrine signaling. Recently, Tsukushi (TSK) was identified as a new hepatokine that is induced by obesity and cold exposure. It was proposed that TSK controls sympathetic innervation and thermogenesis in brown adipose tissue (BAT) and that loss of TSK protects against diet-induced obesity and improves glucose homeostasis. Here we report the impact of deleting and/or overexpressing TSK on BAT thermogenic capacity, body weight regulation, and glucose homeostasis. Methods We measured the expression of thermogenic genes and markers of BAT innervation and activation in TSK-null and TSK-overexpressing mice. Body weight, body temperature, and parameters of glucose homeostasis were also assessed in the context of TSK loss and overexpression. Results The loss of TSK did not affect the thermogenic activation of BAT. We found that TSK-null mice were not protected against the development of obesity and did not show improvement in glucose tolerance. The overexpression of TSK also failed to modulate thermogenesis, body weight gain, and glucose homeostasis in mice
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