Smooth Initial Conditions from Weak Gravity

CMB measurements reveal an unnaturally smooth early universe. We propose a mechanism to make this smoothness natural by weakening the strength of gravity at early times, and therefore altering which initial conditions have low entropy.Comment: 14 pages, 5 figures. Minor changes, version appearing in PL

Cosmological Moduli Dynamics

Low energy effective actions arising from string theory typically contain many scalar fields, some with a very complicated potential and others with no potential at all. The evolution of these scalars is of great interest. Their late time values have a direct impact on low energy observables, while their early universe dynamics can potentially source inflation or adversely affect big bang nucleosynthesis. Recently, classical and quantum methods for fixing the values of these scalars have been introduced. The purpose of this work is to explore moduli dynamics in light of these stabilization mechanisms. In particular, we explore a truncated low energy effective action that models the neighborhood of special points (or more generally loci) in moduli space, such as conifold points, where extra massless degrees of freedom arise. We find that the dynamics has a surprisingly rich structure - including the appearance of chaos - and we find a viable mechanism for trapping some of the moduli.Comment: 35 pages, 14 figures, references adde

Families of Quintic Calabi-Yau 3-Folds with Discrete Symmetries

At special loci in their moduli spaces, Calabi-Yau manifolds are endowed with discrete symmetries. Over the years, such spaces have been intensely studied and have found a variety of important applications. As string compactifications they are phenomenologically favored, and considerably simplify many important calculations. Mathematically, they provided the framework for the first construction of mirror manifolds, and the resulting rational curve counts. Thus, it is of significant interest to investigate such manifolds further. In this paper, we consider several unexplored loci within familiar families of Calabi-Yau hypersurfaces that have large but unexpected discrete symmetry groups. By deriving, correcting, and generalizing a technique similar to that of Candelas, de la Ossa and Rodriguez-Villegas, we find a calculationally tractable means of finding the Picard-Fuchs equations satisfied by the periods of all 3-forms in these families. To provide a modest point of comparison, we then briefly investigate the relation between the size of the symmetry group along these loci and the number of nonzero Yukawa couplings. We include an introductory exposition of the mathematics involved, intended to be accessible to physicists, in order to make the discussion self-contained.Comment: 54 pages, 3 figure

Biomarkers of dementia in obstructive sleep apnea

Epidemiologic and mechanistic evidence is increasingly supporting the notion that obstructive sleep apnea is a risk factor for dementia. Hence, the identification of patients at risk of cognitive decline due to obstructive sleep apnea may significantly improve preventive strategies and treatment decisionmaking. Cerebrospinal fluid and blood biomarkers obtained through genomic, proteomic and metabolomic approaches are improving the ability to predict incident dementia. Therefore, fluid biomarkers have the potential to predict vulnerability to neurodegeneration in individuals with obstructive sleep apnea, as well as deepen our understanding of pathophysiological processes linking obstructive sleep apnea and dementia. Many fluid biomarkers linked to Alzheimer’s disease and vascular dementia show abnormal levels in individuals with obstructive sleep apnea, suggesting that these conditions share common underlying mechanisms, including amyloid and tau protein neuropathology, inflammation, oxidative stress, and metabolic disturbances. Markers of these processes include amyloid-β, tau proteins, inflammatory cytokines, acute-phase proteins, antioxydants and oxidized products, homocysteine and clusterin (apolipoprotein J). Thus, these biomarkers may have the ability to identify adults with obstructive sleep apnea at high risk of dementia and provide an opportunity for therapeutic intervention. Large cohort studies are necessary to establish a specific fluid biomarker panel linking obstructive sleep apnea to dementia risk

Conservation Laws in Doubly Special Relativity

Motivated by various theoretical arguments that the Planck energy (Ep - 10^19 GeV) - should herald departures from Lorentz invariance, and the possibility of testing these expectations in the not too distant future, two so-called "Doubly Special Relativity" theories have been suggested -- the first by Amelino-Camelia (DSR1) and the second by Smolin and Magueijo (DSR2). These theories contain two fundamental scales -- the speed of light and an energy usually taken to be Ep. The symmetry group is still the Lorentz group, but in both cases acting nonlinearly on the energy-momentum sector. Accordingly, since energy and momentum are no longer additive quantities, finding their values for composite systems (and hence finding the correct conservation laws) is a nontrivial matter. Ultimately it is these possible deviations from simple linearly realized relativistic kinematics that provide the most promising observational signal for empirically testing these models. Various investigations have narrowed the conservation laws down to two possibilities per DSR theory. We derive unique exact results for the energy-momentum of composite systems in both DSR1 and DSR2, and indicate the general strategy for arbitrary nonlinear realizations of the Lorentz group.Comment: V2: Extensive revisions: merged with gr-qc/0205093, new author added, references added, discussion amplified. 4 pages, revtex4; V3: Revised in response to referee comments; no physics changes; version to appear in Physical Review

Dynamic amyloid and metabolic signatures of delayed recall performance within the clinical spectrum of Alzheimer’s disease

Associations between pathophysiological events and cognitive measures provide insights regarding brain networks affected during the clinical progression of Alzheimer’s disease (AD). In this study, we assessed patients’ scores in two delayed episodic memory tests, and investigated their associations with regional amyloid deposition and brain metabolism across the clinical spectrum of AD. We assessed the clinical, neuropsychological, structural, and positron emission tomography (PET) baseline measures of participants from the Alzheimer’s Disease Neuroimaging Initiative. Subjects were classified as cognitively normal (CN), or with early (EMCI) or late (LMCI) mild cognitive impairment, or AD dementia. The memory outcome measures of interest were logical memory 30 min delayed recall (LM30) and Rey Auditory Verbal Learning Test 30 min delayed recall (RAVLT30). Voxel-based [18F]florbetapir and [18F]FDG uptake-ratio maps were constructed and correlations between PET images and cognitive scores were calculated. We found that EMCI individuals had LM30 scores negatively correlated with [18F]florbetapir uptake on the right parieto-occipital region. LMCI individuals had LM30 scores positively associated with left lateral temporal lobe [18F]FDG uptake, and RAVLT30 scores positively associated with [18F]FDG uptake in the left parietal lobe and in the right enthorhinal cortex. Additionally, LMCI individuals had LM30 scores negatively correlated with [18F]florbetapir uptake in the right frontal lobe. For the AD group, [18F]FDG uptake was positively correlated with LM30 in the left temporal lobe and with RAVLT30 in the right frontal lobe, and [18F]florbetapir uptake was negatively correlated with LM30 scores in the right parietal and left frontal lobes. The results show that the association between regional brain metabolism and the severity of episodic memory deficits is dependent on the clinical disease stage, suggesting a dynamic relationship between verbal episodic memory deficits, AD pathophysiology, and clinical disease stages

Cerebellar tRNA methyltransferases: A development study

Developmental patterns of homologous and heterologous tRNA methylation by cerebellar tRNA methyltransferases are described. The study revealed that: (a) homologous tRNA methylation results in the predominant formation of N2-methyl-guanine and 1-methyladenine; (b) tRNA methyltransferases of bulk-isolated Purkinje and granule cells methylate E. coli tRNAglu2 in vitro in a characteristic manner, and (c) the methylation of 8-day-old cerebellar, cortical and hepatic tRNA in vivo yields tRNAs containing different proportions of methylated bases. The findings suggest that the presumably cell-specific populations of cerebellar tRNA methyltransferases continue to alter their substrate recognition characteristics up to and beyond the first month of post-natal life.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23318/1/0000257.pd

The Comprehensive Assessment of Neurodegeneration and Dementia: Canadian Cohort Study.

BackgroundThe Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort study of the Canadian Consortium on Neurodegeneration in Aging (CCNA) is a national initiative to catalyze research on dementia, set up to support the research agendas of CCNA teams. This cross-country longitudinal cohort of 2310 deeply phenotyped subjects with various forms of dementia and mild memory loss or concerns, along with cognitively intact elderly subjects, will test hypotheses generated by these teams.MethodsThe COMPASS-ND protocol, initial grant proposal for funding, fifth semi-annual CCNA Progress Report submitted to the Canadian Institutes of Health Research December 2017, and other documents supplemented by modifications made and lessons learned after implementation were used by the authors to create the description of the study provided here.ResultsThe CCNA COMPASS-ND cohort includes participants from across Canada with various cognitive conditions associated with or at risk of neurodegenerative diseases. They will undergo a wide range of experimental, clinical, imaging, and genetic investigation to specifically address the causes, diagnosis, treatment, and prevention of these conditions in the aging population. Data derived from clinical and cognitive assessments, biospecimens, brain imaging, genetics, and brain donations will be used to test hypotheses generated by CCNA research teams and other Canadian researchers. The study is the most comprehensive and ambitious Canadian study of dementia. Initial data posting occurred in 2018, with the full cohort to be accrued by 2020.ConclusionAvailability of data from the COMPASS-ND study will provide a major stimulus for dementia research in Canada in the coming years

The dementia-associated APOE ε4 allele is not associated with rapid eye movement sleep behavior disorder

The present study aimed to examine whether the APOE ε4 allele, associated with dementia with Lewy bodies (DLB), and possibly with dementia in Parkinson's disease (PD), is also associated with idiopathic rapid eye movement sleep behavior disorder (RBD). Two single nucleotide polymorphisms, rs429358 and rs7412, were genotyped in RBD patients (n = 480) and in controls (n = 823). APOE ε4 allele frequency was 0.14 among RBD patients and 0.13 among controls (OR = 1.11, 95% CI: 0.88-1.40, p = 0.41). APOE ε4 allele frequencies were similar in those who converted to DLB (0.14) and those who converted to Parkinson's disease (0.12) or multiple system atrophy (0.14, p = 1.0). The APOE ε4 allele is neither a risk factor for RBD nor it is associated with conversion from RBD to DLB or other synucleinopathies