Resonant and Non-Resonant Modulated Amplitude Waves for Binary Bose-Einstein Condensates in Optical Lattices

We consider a system of two Gross-Pitaevskii (GP) equations, in the presence of an optical-lattice (OL) potential, coupled by both nonlinear and linear terms. This system describes a Bose-Einstein condensate (BEC) composed of two different spin states of the same atomic species, which interact linearly through a resonant electromagnetic field. In the absence of the OL, we find plane-wave solutions and examine their stability. In the presence of the OL, we derive a system of amplitude equations for spatially modulated states which are coupled to the periodic potential through the lowest-order subharmonic resonance. We determine this averaged system's equilibria, which represent spatially periodic solutions, and subsequently examine the stability of the corresponding solutions with direct simulations of the coupled GP equations. We find that symmetric (equal-amplitude) and asymmetric (unequal-amplitude) dual-mode resonant states are, respectively, stable and unstable. The unstable states generate periodic oscillations between the two condensate components, which is possible only because of the linear coupling between them. We also find four-mode states, but they are always unstable. Finally, we briefly consider ternary (three-component) condensates.Comment: 16 pages, 4 figures (some of which have multiple parts), to appear in Physica D; streamlined paper; added some references and discussion concerning experimental realizations of this work; higher-resolution copies of a couple figures are available on the version of the document downloadable from http://www.math.gatech.edu/~mason

Tracing protons through the Galactic magnetic field: a clue for charge composition of ultra-high energy cosmic rays

We reconstruct the trajectories of ultra-high energy cosmic rays (UHECR) - observed by the AGASA experiment - in the Galactic magnetic field assuming that all particles have the same charge. We then study correlations between the reconstructed events and BL Lacs. The correlations have significance below 10^{-3} in the case of particles with charge +1. In the case of charge -1 the correlations are absent. We interpret this as evidence that protons are present in the flux of UHECR. Observed correlation provides an independent evidence that BL Lacs emit UHECR.Comment: 6 pages, 3 figures, LaTe

Effective interaction between helical bio-molecules

The effective interaction between two parallel strands of helical bio-molecules, such as deoxyribose nucleic acids (DNA), is calculated using computer simulations of the "primitive" model of electrolytes. In particular we study a simple model for B-DNA incorporating explicitly its charge pattern as a double-helix structure. The effective force and the effective torque exerted onto the molecules depend on the central distance and on the relative orientation. The contributions of nonlinear screening by monovalent counterions to these forces and torques are analyzed and calculated for different salt concentrations. As a result, we find that the sign of the force depends sensitively on the relative orientation. For intermolecular distances smaller than $6\AA$ it can be both attractive and repulsive. Furthermore we report a nonmonotonic behaviour of the effective force for increasing salt concentration. Both features cannot be described within linear screening theories. For large distances, on the other hand, the results agree with linear screening theories provided the charge of the bio-molecules is suitably renormalized.Comment: 18 pages, 18 figures included in text, 100 bibliog

Systems genetics identifies a role for Cacna2d1 regulation in elevated intraocular pressure and glaucoma susceptibility

Glaucoma is a multi-factorial blinding disease in which genetic factors play an important role. Elevated intraocular pressure is a highly heritable risk factor for primary open angle glaucoma and currently the only target for glaucoma therapy. Our study helps to better understand underlying genetic and molecular mechanisms that regulate intraocular pressure, and identifies a new candidate gene, Cacna2d1, that modulates intraocular pressure and a promising therapeutic, pregabalin, which binds to CACNA2D1 protein and lowers intraocular pressure significantly. Because our study utilizes a genetically diverse population of mice with kno

Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r =-0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r =-0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation

Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations

Primary open angle glaucoma (POAG) is a complex disease with a major genetic contribution. Its prevalence varies greatly among ethnic groups, and is up to five times more frequent in black African populations compared to Europeans. So far, worldwide efforts to elucidate the genetic complexity of POAG in African populations has been limited. We conducted a genome-wide association study in 1113 POAG cases and 1826 controls from Tanzanian, South African and African American study samples. Apart from confirming evidence of association at TXNRD2 (rs16984299; OR[T] 1.20; P = 0.003), we found that a genetic risk score combining the effects of the 15 previously reported POAG loci was significantly associated with POAG in our samples (OR 1.56; 95% CI 1.26–1.93; P = 4.79 × 10−5). By genome-wide association testing we identified a novel candidate locus, rs141186647, harboring EXOC4 (OR[A] 0.48; P = 3.75 × 10−8), a gene transcribing a component of the exocyst complex involved in vesicle transport. The low frequency and high degree of genetic heterogeneity at this region hampered validation of this finding in predominantly West-African replication sets. Our results suggest that established genetic risk factors play a role in African POAG, however, they do not explain the higher disease load. The high heterogeneity within Africans remains a challenge to identify the genetic commonalities for POAG in this ethnicity, and demands studies of extremely large size

Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

The association between circulating antibodies against domain I of beta2-glycoprotein I and thrombosis: an international multicenter study

BACKGROUND: Diagnosis of the antiphospholipid syndrome (APS) is difficult as a result of limited specificity of existing assays for detecting clinically relevant antiphospholipid antibodies. Anti-beta2-glycoprotein I (beta 2GPI) antibodies play a central role in the disease process of APS. OBJECTIVES: We have investigated the relation between antiphospholipid antibodies with specificity for domain I of beta 2GPI and thrombosis/pregnancy morbidity in an international multicenter study. PATIENTS/METHODS: Four hundred and seventy-seven patients derived from nine different centres met the inclusion criterion of having anti-beta 2GPI antibodies in their plasma/serum. Clinical data and results of tests for lupus anticoagulant, anti-cardiolipin antibodies and anti-beta 2GPI antibodies were established at the different centres of inclusion. After being re-tested for the presence of IgG and/or IgM anti-beta 2GPI antibodies, the samples were tested for the presence of IgG-directed against domain I of beta 2GPI and results were correlated with the thrombotic and obstetric history. RESULTS: Re-testing for the presence of anti-beta 2GPI antibodies resulted in inclusion of 442/477 patients. IgG class anti-domain I antibodies were present in plasma of 243/442 patients (55%). 201/243 (83%) had a history of thrombosis. This resulted in an odds ratio of 3.5 (2.3-5.4, 95% confidence interval) for thrombosis. Anti-domain I IgG antibodies were also significantly correlated with obstetric complications [odds ratio: 2.4 (1.4-4.3, 95% confidence interval)]. CONCLUSION: In this multicenter study, the detection of IgG antibodies that are directed against domain I of beta 2GPI proved to be more strongly associated with thrombosis and obstetric complications than those detected using the standard anti-beta 2GPI antibody assay