An adaptive inelastic magnetic mirror for Bose-Einstein condensates

We report the reflection and focussing of a Bose-Einstein condensate by a new pulsed magnetic mirror. The mirror is adaptive, inelastic, and of extremely high optical quality. The deviations from specularity are less than 0.5 mrad rms, making this the best atomic mirror demonstrated to date. We have also used the mirror to realize the analog of a beam-expander, producing an ultra-cold collimated fountain of matter wavesComment: 4 pages, 4 figure

Maternal uniparental isodisomy of chromosome 6 unmasks a novel variant in TULP1 in a patient with early onset retinal dystrophy

Purpose: Inherited retinal dystrophies are a clinically and genetically heterogeneous group of disorders. Molecular diagnosis has proven utility for affected individuals. In this study, we report an individual enrolled in the Australian Inherited Retinal Disease Registry and DNA Bank diagnosed with clinical features overlapping between Leber congenital amaurosis and retinitis pigmentosa. Methods: DNA from the proband was sequenced using a gene panel for inherited retinal disorders, and a single nucleotide polymorphism (SNP) array was conducted to detect the presence of deletions and uniparental disomy. Results: We identified a novel homozygous variant (c.524dupC, p.(Pro176ThrfsTer7)) in TULP1 resulting from maternal uniparental isodisomy of chromosome 6. The patient had clinical features consistent with biallelic pathogenic variants in TULP1, including congenital nystagmus, night blindness, non-recordable electroretinogram, mild myopia, and mild peripheral pigmentary changes in the fundus. Conclusions: This is the first report of uniparental disomy 6 and a homozygous variant in TULP1 associated with a rod-cone dystrophy. Molecular diagnosis of inherited retinal dystrophies is essential to inform the mode of transmission and clinical management, and to identify potential candidates for future gene-specific therapies.Emmanuelle Souzeau, Jennifer A. Thompson, Terri L. McLaren, John N. De Roach, Christopher P. Barnett, Tina M. Lamey, Jamie E. Crai

A quantum mechanical description of the experiment on the observation of gravitationally bound states

Quantum states in the Earth's gravitational field were observed, when ultra-cold neutrons fall under gravity. The experimental results can be described by the quantum mechanical scattering model as it is presented here. We also discuss other geometries of the experimental setup which correspond to the absence or the reversion of gravity. Since our quantum mechanical model describes, particularly, the experimentally realized situation of reversed gravity quantitatively, we can practically rule out alternative explanations of the quantum states in terms of pure confinement effects.Comment: LaTeX, 10 pages, 4 figures, v2: references adde

Velocity-selective sublevel resonance of atoms with an array of current-carrying wires

Resonance transitions between the Zeeman sublevels of optically-polarized Rb atoms traveling through a spatially periodic magnetic field are investigated in a radio-frequency (rf) range of sub-MHz. The atomic motion induces the resonance when the Zeeman splitting is equal to the frequency at which the moving atoms feel the magnetic field oscillating. Additional temporal oscillation of the spatially periodic field splits a motion-induced resonance peak into two by an amount of this oscillation frequency. At higher oscillation frequencies, it is more suitable to consider that the resonance is mainly driven by the temporal field oscillation, with its velocity-dependence or Doppler shift caused by the atomic motion through the periodic field. A theoretical description of motion-induced resonance is also given, with emphasis on the translational energy change associated with the internal transition.Comment: 7 pages, 3 figures, final versio

Characterising splicing defects of ABCA4 variants within exons 13–50 in patient-derived fibroblasts

The ATP-binding cassette subfamily A member 4 gene (ABCA4)-associated retinopathy, Stargardt disease, is the most common monogenic inherited retinal disease. Given the pathogenicity of numerous ABCA4 variants is yet to be examined and a significant proportion (more than 15%) of ABCA4 variants are categorized as splice variants in silico, we therefore established a fibroblast-based splice assay to analyze ABCA4 variants in an Australian Stargardt disease cohort and characterize the pathogenic mechanisms of ABCA4 variants. A cohort of 67 patients clinically diagnosed with Stargardt disease was recruited. Genomic DNA was analysed using a commercial panel for ABCA4 variant detection and the consequences of ABCA4 variants were predicted in silico. Dermal fibroblasts were propagated from skin biopsies, total RNA was extracted and the ABCA4 transcript was amplified by RT-PCR. Our analysis identified a total of 67 unique alleles carrying 74 unique variants. The most prevalent splice-affecting complex allele c.[5461-10T > C; 5603A > T] was carried by 10% of patients in a compound heterozygous state. ABCA4 transcripts from exon 13 to exon 50 were readily detected in fibroblasts. In this region, aberrant splicing was evident in 10 out of 57 variant transcripts (18%), carried by 19 patients (28%). Patient-derived fibroblasts provide a feasible platform for identification of ABCA4 splice variants located within exons 13–50. Experimental evidence of aberrant splicing contributes to the pathogenic classification for ABCA4 variants. Moreover, identification of variants that affect splicing processes provides opportunities for intervention, in particular antisense oligonucleotide-mediated splice correction

Quantum gates with neutral atoms: Controlling collisional interactions in time dependent traps

We theoretically study specific schemes for performing a fundamental two-qubit quantum gate via controlled atomic collisions by switching microscopic potentials. In particular we calculate the fidelity of a gate operation for a configuration where a potential barrier between two atoms is instantaneously removed and restored after a certain time. Possible implementations could be based on microtraps created by magnetic and electric fields, or potentials induced by laser light.Comment: 10 pages, 3 figure

Determinants of disease penetrance in PRPF31-associated retinopathy

Retinitis pigmentosa 11 (RP11) is caused by dominant mutations in PRPF31, however a significant proportion of mutation carriers do not develop retinopathy. Here, we investigated the relationship between CNOT3 polymorphism, MSR1 repeat copy number and disease penetrance in RP11 patients and non-penetrant carriers (NPCs). We further characterized PRPF31 and CNOT3 expression in fibroblasts from eight RP11 patients and one NPC from a family carrying the c.1205C>T variant. Retinal organoids (ROs) and retinal pigment epithelium (RPE) were differentiated from induced pluripotent stem cells derived from RP11 patients, an NPC and a control subject. All RP11 patients were homozygous for the 3-copy MSR1 repeat in the PRPF31 promoter, while 3/5 NPCs carried a 4-copy MSR1 repeat. The CNOT3 rs4806718 genotype did not correlate with disease penetrance. PRFP31 expression declined with age in adult cadaveric retina. PRPF31 and CNOT3 expression was reduced in RP11 fibroblasts, RO and RPE compared with controls. Both RP11 and NPC RPE displayed shortened primary cilia compared with controls, however a subpopulation of cells with normal cilia lengths was present in NPC RPE monolayers. Our results indicate that RP11 non-penetrance is associated with the inheritance of a 4-copy MSR1 repeat, but not with CNOT3 polymorphisms

A novel method to produce kiss-bonds in composites components for NDI and characterisation purposes

Kiss-bonds (kissing bonds) are a defect type that feature a localised loss of structural continuity within the material, yet the material remains in intimate contact across the defect. Typically, shear and normal tensile stresses cannot be conducted across such defects (although, pure compressive stresses are possible). Kiss-bond defects are difficult to detect reliably – both within the bulk of the material (interlaminar) and within bond-lines of adhesively bonded joints or repairs – using conventional Non-Destructive Inspection (NDI) techniques. Compounding this issue is the lack of a reliable technique to create representative kiss-bond defects in a controlled fashion for the purpose of NDI equipment calibration or development, or scientific investigation. A novel method for manufacturing composite material test panels with kiss-bond defects (for research or NDI calibration, for example) in a controlled and repeatable fashion has been developed. Small areas of two adjacent pre-preg plies were pre-cured before being incorporated within a laminate. During consolidation, no bonding occurs between the pre-cured areas, thus creating a kiss-bond defect of known geometry. Test panels with 6 × 6 mm and 10 × 10 mm kiss-bond defects were manufactured. The robustness of the technique was verified using ultrasonic and laser shearography NDI methods; 7 of the 10 manufactured defects were classified as kiss-bonds, with the remaining 3 identified as dis-bonds

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Genome-wide association study and meta-analysis identify loci associated with ventricular and supraventricular ectopy

The genetic basis of supraventricular and ventricular ectopy (SVE, VE) remains largely uncharacterized, despite established genetic mechanisms of arrhythmogenesis. To identify novel genetic variants associated with SVE/VE in ancestrally diverse human populations, we conducted a genome-wide association study of electrocardiographically identified SVE and VE in five cohorts including approximately 43,000 participants of African, European and Hispanic/Latino ancestry. In thirteen ancestry-stratified subgroups, we tested multivariable-adjusted associations of SVE and VE with single nucleotide polymorphism (SNP) dosage. We combined subgroup-specific association estimates in inverse variance-weighted, fixed-effects and Bayesian meta-analyses. We also combined fixed-effects meta-analytic t-test statistics for SVE and VE in multi-trait SNP association analyses. No loci reached genome-wide significance in trans-ethnic meta-analyses. However, we found genome-wide significant SNPs intronic to an apoptosis-enhancing gene previously associated with QRS interval duration (FAF1; lead SNP rs7545860; effect allele frequency = 0.02; P = 2.0 × 10-8) in multi-trait analysis among European ancestry participants and near a locus encoding calcium-dependent glycoproteins (DSC3; lead SNP rs8086068; effect allele frequency = 0.17) in meta-analysis of SVE (P = 4.0 × 10-8) and multi-trait analysis (P = 2.9 × 10-9) among African ancestry participants. The novel findings suggest several mechanisms by which genetic variation may predispose to ectopy in humans and highlight the potential value of leveraging pleiotropy in future studies of ectopy-related phenotypes