Monodromy in the CMB: Gravity Waves and String Inflation

We present a simple mechanism for obtaining large-field inflation, and hence a gravitational wave signature, from string theory compactified on twisted tori. For Nil manifolds, we obtain a leading inflationary potential proportional to phi^(2/3) in terms of the canonically normalized field phi, yielding predictions for the tilt of the power spectrum and the tensor-to-scalar ratio, $n_s\approx 0.98$ and $r\approx 0.04$ with 60 e-foldings of inflation; we note also the possibility of a variant with a candidate inflaton potential proportional to phi^(2/5). The basic mechanism involved in extending the field range -- monodromy in D-branes as they move in circles on the manifold -- arises in a more general class of compactifications, though our methods for controlling the corrections to the slow-roll parameters require additional symmetries.Comment: 43 pages, latex. 4 figure

Uromodulin is expressed in renal primary cilia and UMOD mutations result in decreased ciliary uromodulin expression

Uromodulin (UMOD) mutations are responsible for three autosomal dominant tubulo-interstitial nephropathies including medullary cystic kidney disease type 2 (MCKD2), familial juvenile hyperuricemic nephropathy and glomerulocystic kidney disease. Symptoms include renal salt wasting, hyperuricemia, gout, hypertension and end-stage renal disease. MCKD is part of the ‘nephronophthisis-MCKD complex', a group of cystic kidney diseases. Both disorders have an indistinguishable histology and renal cysts are observed in either. For most genes mutated in cystic kidney disease, their proteins are expressed in the primary cilia/basal body complex. We identified seven novel UMOD mutations and were interested if UMOD protein was expressed in the primary renal cilia of human renal biopsies and if mutant UMOD would show a different expression pattern compared with that seen in control individuals. We demonstrate that UMOD is expressed in the primary cilia of renal tubules, using immunofluorescent studies in human kidney biopsy samples. The number of UMOD-positive primary cilia in UMOD patients is significantly decreased when compared with control samples. Additional immunofluorescence studies confirm ciliary expression of UMOD in cell culture. Ciliary expression of UMOD is also confirmed by electron microscopy. UMOD localization at the mitotic spindle poles and colocalization with other ciliary proteins such as nephrocystin-1 and kinesin family member 3A is demonstrated. Our data add UMOD to the group of proteins expressed in primary cilia, where mutations of the gene lead to cystic kidney diseas

Association of urinary uromodulin with kidney function decline and mortality: the health ABC study .

BackgroundUrine uromodulin (uUMOD) is a protein secreted by the kidney tubule. Recent studies have suggested that higher uUMOD may be associated with improved kidney and mortality outcomes.MethodsUsing a case-cohort design, we evaluated the association between baseline uUMOD levels and ≥ 30% estimated glomerular filtration rate (eGFR) decline, incident chronic kidney disease (CKD), rapid kidney function decline, and mortality using standard and modified Cox proportional hazards regression.ResultsThe median value of uUMOD was 25.8 µg/mL, mean age of participants was 74 years, 48% were women, and 39% were black. Persons with higher uUMOD had lower prevalence of diabetes and coronary artery disease (CAD), and had lower systolic blood pressure. Persons with higher uUMOD also had higher eGFR, lower urinary albumin to creatinine ratio (ACR), and lower C-reactive protein (CRP). There was no association of uUMOD with > 30% eGFR decline. In comparison to those in the lowest quartile of uUMOD, those in the highest quartile had a significantly (53%) lower risk of incident CKD (CI 73%, 18%) and a 51% lower risk of rapid kidney function decline (CI 76%, 1%) after multivariable adjustment. Higher uUMOD was associated with lower risk of mortality in demographic adjusted models, but not after multivariable adjustment.ConclusionHigher levels of uUMOD are associated with lower risk of incident CKD and rapid kidney function decline. Additional studies are needed in the general population and in persons with advanced CKD to confirm these findings.


The role of renal transporters and novel regulatory interactions in the TAL that control blood pressure

Hypertension (HTN), a major public health issue is currently the leading factor in the global burden of disease, where associated complications account for 9.4 million deaths worldwide every year (98). Excessive dietary salt intake is among the environmental factors that contribute to HTN, known as salt sensitivity. The heterogeneity of salt sensitivity and the multiple mechanisms that link high salt intake to increases in blood pressure are of upmost importance for therapeutic application. A continual increase in the kidney's reabsorption of sodium (Na+) relies on sequential actions at various segments along the nephron. When the distal segments of the nephron fail to regulate Na+, the effects on Na+ homeostasis are unfavourable. We propose that the specific nephron region where increased active uptake occurs as a result of variations in Na+ reabsorption is at the thick ascending limb of the loop of Henle (TAL). The purpose of this review is to urge the consideration of the TAL that contributes to the pathophysiology of salt sensitive HTN. Further research in this area will enable development of a therapeutic application for targeted treatment

Axions as Quintessence in String Theory

We construct a model of quintessence in string theory based on the idea of axion monodromy as discussed by McAllister, Silverstein and Westphal arXiv:0808.0706. In the model, the quintessence field is an axion whose shift symmetry is broken by the presence of 5-branes which are placed in highly warped throats. This gives rise to a potential for the axion field which is slowly varying, even after incorporating the effects of moduli stabilization and supersymmetry breaking. We find that the resulting time dependence in the equation of state of Dark Energy is potentially detectable, depending on the initial conditions. The model has many very light extra particles which live in the highly warped throats, but these are hard to detect. A signal in the rotation of the CMB polarization can also possibly arise.Comment: 41 pages, 1 figure, v2: references adde