Higher Semiadditive Algebraic K-Theory and Redshift

We define higher semiadditive algebraic K-theory, a variant of algebraic K-theory that takes into account higher semiadditive structure, as enjoyed for example by the $K(n)$- and $T(n)$-local categories. We prove that it satisfies a form of the redshift conjecture. Namely, that if $R$ is a ring spectrum of height $\leq n$, then its semiadditive K-theory is of height $\leq n+1$. Under further hypothesis on $R$, which are satisfied for example by the Lubin-Tate spectrum $E_n$, we show that its semiadditive algebraic K-theory is of height exactly $n+1$. Finally, we connect semiadditive K-theory to $T(n+1)$-localized K-theory, showing that they coincide for any $p$-invertible ring spectrum and for the completed Johnson-Wilson spectrum $\widehat{E(n)}$.Comment: v2: Added Theorem D and E concerning the higher semiadditive K-theory of completed Johnson-Wilson at any height, and other small improvements. v1: 44 pages, comments are welcome

Descent and Cyclotomic Redshift for Chromatically Localized Algebraic K-theory

We prove that $T(n+1)$-localized algebraic $K$-theory satisfies descent for $\pi$-finite $p$-group actions on stable $\infty$-categories of chromatic height up to $n$, extending a result of Clausen-Mathew-Naumann-Noel for $p$-groups. Using this, we show that it sends $T(n)$-local Galois extensions to $T(n+1)$-local Galois extensions. Furthermore, we show that it sends cyclotomic extensions of height $n$ to cyclotomic extensions of height $n+1$, extending a result of Bhatt-Clausen-Mathew for $n=0$. As a consequence, we deduce that $K(n+1)$-localized $K$-theory satisfies hyperdescent along the cyclotomic tower of any $T(n)$-local ring. Counterexamples to such cyclotomic hyperdescent for $T(n+1)$-localized $K$-theory were constructed by Burklund, Hahn, Levy and the third author, thereby disproving the telescope conjecture.Comment: 66 pages, comments are welcom

Change of Scale and Forecasting with the Control-Function Method in Logit Models

Endogeneity is a model misspecification that precludes the consistent estimation of the model parameters. The control-function method is the most suitable tool to address endogeneity for several discrete choice models that are relevant in transportation research. However, the estimators obtained with the control-function method are consistent only up to a scale. In this paper, we first depict the determinants of this change of scale by adapting an existing result for omitted orthogonal attributes in logit models. Then, we study the problem of forecasting under these circumstances. We show that a procedure proposed in previous literature may lead to significant biases, and we suggest novel alternatives to be used with synthetic populations. We use Monte Carlo experimentation and real data on residential location choice to illustrate these results. The paper finishes by summarizing the findings of this investigation and suggesting future lines of research in this area.MIT-Portugal Progra

Regulation of per and cry Genes Reveals a Central Role for the D-Box Enhancer in Light-Dependent Gene Expression

Light serves as a key environmental signal for synchronizing the circadian clock with the day night cycle. The zebrafish represents an attractive model for exploring how light influences the vertebrate clock mechanism. Direct illumination of most fish tissues and cell lines induces expression of a broad range of genes including DNA repair, stress response and key clock genes. We have previously identified D- and E-box elements within the promoter of the zebrafish per2 gene that together direct light-induced gene expression. However, is the combined regulation by E- and D-boxes a general feature for all light-induced gene expression? We have tackled this question by examining the regulation of additional light-inducible genes. Our results demonstrate that with the exception of per2, all other genes tested are not induced by light upon blocking of de novo protein synthesis. We reveal that a single D-box serves as the principal light responsive element within the cry1a promoter. Furthermore, upon inhibition of protein synthesis D-box mediated gene expression is abolished while the E-box confers light driven activation as observed in the per2 gene. Given the existence of different photoreceptors in fish cells, our results implicate the D-box enhancer as a general convergence point for light driven signaling

Thioredoxin-mimetic peptide CB3 lowers MAPKinase activity in the Zucker rat brain

AbstractDiabetes is a high risk factor for dementia. High glucose may be a risk factor for dementia even among persons without diabetes, and in transgenic animals it has been shown to cause a potentiation of indices that are pre-symptomatic of Alzheimer′s disease. To further elucidate the underlying mechanisms linking inflammatory events elicited in the brain during oxidative stress and diabetes, we monitored the activation of mitogen-activated kinsase (MAPKs), c-jun NH2-terminal kinase (JNK), p38 MAP kinases (p38MAPK), and extracellular activating kinsae1/2 (ERK1/2) and the anti-inflammatory effects of the thioredoxin mimetic (TxM) peptides, Ac-Cys-Pro-Cys-amide (CB3) and Ac-Cys-Gly-Pro-Cys-amide (CB4) in the brain of male leptin-receptor-deficient Zucker diabetic fatty (ZDF) rats and human neuroblastoma SH-SY5Y cells. Daily i.p. injection of CB3 to ZDF rats inhibited the phosphorylation of JNK and p38MAPK, and prevented the expression of thioredoxin-interacting-protein (TXNIP/TBP-2) in ZDF rat brain. Although plasma glucose/insulin remained high, CB3 also increased the phosphorylation of AMP-ribose activating kinase (AMPK) and inhibited p70S6K kinase in the brain. Both CB3 and CB4 reversed apoptosis induced by inhibiting thioredoxin reductase as monitored by decreasing caspase 3 cleavage and PARP dissociation in SH-SY5Y cells. The decrease in JNK and p38MAPK activity in the absence of a change in plasma glucose implies a decrease in oxidative or neuroinflammatory stress in the ZDF rat brain. CB3 not only attenuated MAPK phosphorylation and activated AMPK in the brain, but it also diminished apoptotic markers, most likely acting via the MAPK–AMPK–mTOR pathway. These results were correlated with CB3 and CB4 inhibiting inflammation progression and protection from oxidative stress induced apoptosis in human neuronal cells. We suggest that by attenuating neuro-inflammatory processes in the brain Trx1 mimetic peptides could become beneficial for preventing neurological disorders associated with diabetes