Supersymmetry and Electroweak breaking from extra dimensions at the TeV-scale

We analyze some features of the role that extra dimensions, of radius $R$ in the TeV$^{-1}$ range, can play in the soft breaking of supersymmetry and the spontaneous breaking of electroweak symmetry. We use a minimal model where the gauge and Higgs sector of the MSSM are living in the bulk of five dimensions and the chiral multiplets in a four-dimensional boundary. Supersymmetry is broken in the bulk by the Scherk-Schwarz mechanism and transmitted to the boundary by radiative corrections. The particle spectrum is completely predicted as a function of a unique $R$-charge. The massless sector corresponds to the pure Standard Model and electroweak symmetry is radiatively broken with a light Higgs weighing \simlt 110 GeV. The $\mu$-problem is solved and Higgsinos, gauginos and heavy Higgses acquire masses $\sim 1/R$. Chiral sfermions acquire radiative squared-masses $\sim \alpha_i/R^2$. The effective potential is explicitly computed in the bulk of extra dimensions and some cosmological consequences can be immediately drawn from it. Gauge coupling running and unification is studied in the presence of Scherk-Schwarz supersymmetry breaking. The unification is similar to that in the supersymmetric theory.Comment: 27 pages, Latex, 7 figures. Minor change

Supersymmetry breaking on orbifolds from Wilson lines

We consider five dimensional theories compactified on the orbifold S^1/Z_2 and prove that spontaneous local supersymmetry breaking by Wilson lines and by the Scherk-Schwarz mechanism are equivalent. Wilson breaking is triggered by the SU(2)_R symmetry which is gauged in off-shell N=2 supergravity by auxiliary fields. The super-Higgs mechanism disposes of the would-be Goldstinos which are absorbed by the gravitinos to become massive. The breaking survives in the flat limit, where we decouple all gravitational interactions, and the theory becomes softly broken global supersymmetry.Comment: 9 pages, some comments in the discussion of the super-Higgs effect and some references adde

Modulation of γ-Secretase Reduces β-Amyloid Deposition in a Transgenic Mouse Model of Alzheimer's Disease

SummaryAlzheimer's disease (AD) is characterized pathologically by the abundance of senile plaques and neurofibrillary tangles in the brain. We synthesized over 1200 novel gamma-secretase modulator (GSM) compounds that reduced Aβ42 levels without inhibiting epsilon-site cleavage of APP and Notch, the generation of the APP and Notch intracellular domains, respectively. These compounds also reduced Aβ40 levels while concomitantly elevating levels of Aβ38 and Aβ37. Immobilization of a potent GSM onto an agarose matrix quantitatively recovered Pen-2 and to a lesser degree PS-1 NTFs from cellular extracts. Moreover, oral administration (once daily) of another potent GSM to Tg 2576 transgenic AD mice displayed dose-responsive lowering of plasma and brain Aβ42; chronic daily administration led to significant reductions in both diffuse and neuritic plaques. These effects were observed in the absence of Notch-related changes (e.g., intestinal proliferation of goblet cells), which are commonly associated with repeated exposure to functional gamma-secretase inhibitors (GSIs)

Phenomenology of Low Quantum Gravity Scale Models

We study some phenomenological implications of models where the scale of quantum gravity effects lies much below the four-dimensional Planck scale. These models arise from M-theory vacua where either the internal space volume is large or the string coupling is very small. We provide a critical analysis of ways to unify electroweak, strong and gravitational interactions in M-theory. We discuss the relations between different scales in two M-vacua: Type I strings and Ho\v rava-Witten supergravity models. The latter allows possibilities for an eleven-dimensional scale at TeV energies with one large dimension below separating our four-dimensional world from a hidden one. Different mechanisms for breaking supersymmetry (gravity mediated, gauge mediated and Scherk-Schwarz mechanisms) are discussed in this framework. Some phenomenological issues such as dark matter (with masses that may vary in time), origin of neutrino masses and axion scale are discussed. We suggest that these are indications that the string scale may be lying in the $10^{10} - 10^{14}$ GeV region.Comment: 32 pages, latex. Minor corrections and improved referencin

Supersymmetry: From the Fermi Scale to the Planck Scale

The physics of supersymmetry is reviewed from the perspective of physics at ever increasing energies. Starting from the minimal supersymmetric extension of the Standard Model at the electroweak scale, we proceed to higher energies seeking to understand the origin of the many model parameters. Supersymmetric grand unification, supergravity, and superstrings are introduced sequentially, and their contribution to the sought explanations is discussed. Typical low-energy supersymmetric models are also presented, along with their possible experimental consequences via direct and indirect processes at high-energy physics experimental facilities. Contents 1. Introduction 2. Low-energy Supersymmetry 3. Supersymmetric Grand Unification 4. Supergravity 5. Superstrings 6. Dynamics 7. Experimental Prospects 8. ConclusionsComment: 61 pages, LaTeX, 11 figures (included). To appear in Reports on Progress in Physic

Receptor-Associated Protein (RAP) Plays a Central Role in Modulating Aβ Deposition in APP/PS1 Transgenic Mice

BACKGROUND: Receptor associated protein (RAP) functions in the endoplasmic reticulum (ER) to assist in the maturation of several membrane receptor proteins, including low density lipoprotein receptor-related protein (LRP) and lipoprotein receptor 11 (SorLA/LR11). Previous studies in cell and mouse model systems have demonstrated that these proteins play roles in the metabolism of the amyloid precursor protein (APP), including processes involved in the generation, catabolism and deposition of beta-amyloid (Abeta) peptides. METHODOLOGY/PRINCIPAL FINDINGS: Mice transgenic for mutant APPswe and mutant presenilin 1 (PS1dE9) were mated to mice with homozygous deletion of RAP. Unexpectedly, mice that were homozygous null for RAP and transgenic for APPswe/PS1dE9 showed high post-natal mortality, necessitating a shift in focus to examine the levels of amyloid deposition in APPswe/PS1dE9 that were hemizygous null for RAP. Immunoblot analysis confirmed 50% reductions in the levels of RAP with modest reductions in the levels of proteins dependent upon RAP for maturation [LRP trend towards a 20% reduction ; SorLA/LR11 statistically significant 15% reduction (p<0.05)]. Changes in the levels of these proteins in the brains of [APPswe/PS1dE9](+/-)/RAP(+/-) mice correlated with 30-40% increases in amyloid deposition by 9 months of age. CONCLUSIONS/SIGNIFICANCE: Partial reductions in the ER chaperone RAP enhance amyloid deposition in the APPswe/PS1dE9 model of Alzheimer amyloidosis. Partial reductions in RAP also affect the maturation of LRP and SorLA/LR11, which are each involved in several different aspects of APP processing and Abeta catabolism. Together, these findings suggest a central role for RAP in Alzheimer amyloidogenesis

Intracellular Trafficking and Synaptic Function of APL-1 in Caenorhabditis elegans

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder primarily characterized by the deposition of b-amyloid plaques in the brain. Plaques are composed of the amyloid-b peptide derived from cleavage of the amyloid precursor protein (APP). Mutations in APP lead to the development of Familial Alzheimer’s Disease (FAD), however, the normal function of this protein has proven elusive. The organism Caenorhabditis elegans is an attractive model as the amyloid precursor-like protein (APL-1) is the single ortholog of APP, and loss of apl-1 leads to a severe molting defect and early larval lethality. Methodology/Principal Findings: We report here that lethality and molting can be rescued by full length APL-1, C-terminal mutations as well as a C-terminal truncation, suggesting that the extracellular region of the protein is essential for viability. RNAi knock-down of apl-1 followed by drug testing on the acetylcholinesterase inhibitor aldicarb showed that loss of apl-1 leads to aldicarb hypersensitivity, indicating a defect in synaptic function. The aldicarb hypersensitivity can be rescued by full length APL-1 in a dose dependent fashion. At the cellular level, kinesins UNC-104/KIF-1A and UNC-116/kinesin-1 are positive regulators of APL-1 expression in the neurons. Knock-down of the small GTPase rab-5 also leads to a dramatic decrease in the amount of apl-1 expression in neurons, suggesting that trafficking from the plasma membrane to the early endosome is important for apl-1 function. Loss of function of a different small GTPase, UNC-108, on the contrary, leads t