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The Sir2 deacetylase modulates organismal life-span in various species. However, the molecular mechanisms by which Sir2 increases longevity are largely unknown. We show that in mammalian cells, the Sir2 homolog SIRT1 appears to control the cellular response to stress by regulating the FOXO family of Forkhead transcription factors, a family of proteins that(More)
We formulate a dynamic mathematical model that describes the interaction of the immune system with the human immunodeficiency virus (HIV) and that permits drug "cocktail " therapies. We derive HIV therapeutic strategies by formulating and analyzing an optimal control problem using two types of dynamic treatments representing reverse transcriptase (RT) in(More)
About NRDC NRDC (Natural Resources Defense Council) is a national nonprofit environmental organization with more than 1.2 million members and online activists. Since 1970, our lawyers, scientists, and other environmental specialists have worked to protect the world's natural resources, public health, and the environment. NRDC has offices in The nation's(More)
Alzheimer's disease (AD) is a neurodegenerative disorder characterized pathologically by progressive neuronal loss, extracellular plaques containing the amyloid-β (Aβ) peptides, and neurofibrillary tangles composed of hyperphosphorylated tau proteins. Aβ is thought to act upstream of tau, affecting its phosphorylation and therefore aggregation state. One of(More)
The signaling pathway from phosphoinositide 3-kinase to the protein kinase Akt controls organismal life-span in invertebrates and cell survival and proliferation in mammals by inhibiting the activity of members of the FOXO family of transcription factors. We show that mammalian FOXO3a also functions at the G2 to M checkpoint in the cell cycle and triggers(More)
State-dependent Riccati equation (SDRE) techniques are rapidly emerging as general design and synthesis methods of nonlinear feedback controllers and estimators for a broad class of nonlinear regulator problems. In essence, the SDRE approach involves mimicking standard linear quadratic regulator (LQR) formulation for linear systems. In particular, the(More)
We present an overview of some concepts and methodologies we believe useful in model-ing HIV pathogenesis. After a brief discussion of motivation for and previous efforts in the development of mathematical models for progression of HIV infection and treatment, we discuss mathematical and statistical ideas relevant to Structured Treatment Interruptions(More)
The FOXO family of transcription factors constitute an evolutionarily conserved subgroup within the larger family known as winged helix or Forkhead transcriptional regulators. Building upon work in the nematode, researchers have uncovered a role for these proteins in a diverse set of cellular responses that include glucose metabolism, stress response, cell(More)
Repetitive mild or "concussive" traumatic brain injury (TBI) can cause substantial neurologic impairment, but the pathological features of this type of injury are not fully understood. We report an experimental model of TBI in which the closed skulls of anesthetized male C57BL/6J mice are struck with an electromagnetically controlled rubber impactor twice(More)