Majorana states in prismatic core-shell nanowires

We consider core-shell nanowires with conductive shell and insulating core, and with polygonal cross section. We investigate the implications of this geometry on Majorana states expected in the presence of proximity-induced superconductivity and an external magnetic field. A typical prismatic nanowire has a hexagonal profile, but square and triangular shapes can also be obtained. The low-energy states are localized at the corners of the cross section, i.e. along the prism edges, and are separated by a gap from higher energy states localized on the sides. The corner localization depends on the details of the shell geometry, i.e. thickness, diameter, and sharpness of the corners. We study systematically the low-energy spectrum of prismatic shells using numerical methods and derive the topological phase diagram as a function of magnetic field and chemical potential for triangular, square, and hexagonal geometries. A strong corner localization enhances the stability of Majorana modes to various perturbations, including the orbital effect of the magnetic field, whereas a weaker localization favorizes orbital effects and reduces the critical magnetic field. The prismatic geometry allows the Majorana zero-energy modes to be accompanied by low-energy states, which we call pseudo Majorana, and which converge to real Majoranas in the limit of small shell thickness. We include the Rashba spin-orbit coupling in a phenomenological manner, assuming a radial electric field across the shell.Comment: 14 pages, 16 figures, accepted for publication in Phys. Rev.

Experimental evaluation of sub-sampling IQ detection for low-level RF control in particle accelerator systems

The low-level radio frequency (LLRF) control system is one of the fundamental parts of a particle accelerator, ensuring the stability of the electro-magnetic (EM) field inside the resonant cavities. It leverages on the precise measurement of the field by in-phase/quadrature (IQ) detection of an RF probe signal from the cavities, usually performed using analogue downconversion. This approach requires a local oscillator (LO) and is subject to hardware non-idealities like mixer nonlinearity and long-term temperature drifts. In this work, we experimentally evaluate IQ detection by direct sampling for the LLRF system of the Polish free electron laser (PolFEL) now under development at the National Centre for Nuclear Research (NCBJ) in Poland. We study the impact of the sampling scheme and of the clock phase noise for a 1.3-GHz input sub-sampled by a 400-MSa/s analogue-to-digital converter (ADC), estimating amplitude and phase stability below 0.01% and nearly 0.01◦, respectively. The results are in line with state-of-the-art implementations, and demonstrate the feasibility of direct sampling for GHz-range LLRF systems

Association of FTO and TMEM18 polymorphisms with overweight and obesity in the population of Polish children

Published Online: 2016-03-16The objective of the study was to verify whether or not FTO rs9939609, rs9926289 and TMEM18 rs4854344, rs6548238, rs2867125 variants are important risk factors for overweight and/or obesity in Polish children aged 6-16 (n=283). FTO rs 9939609 and rs9926289 exhibited a strong codominant obesity-predisposing effect of genotypes homozygous for minor alleles (OR=5.42, 95% CI: 2.04-14.39, p=0.0006). The important finding of the study is increased risk of overweight (OR=5.03, 95% CI: 1.15-21.93, p=0.0306) in individuals homozygous for the minor alleles rs4854344, rs6548238 and rs2867125 in the recessive inheritance model, while no other significant associations between TMEM18 variants and risk of obesity were found. Given the identified interaction TMEM18 genotype × BMI category (p=0.0077), it seems that the effect of homozygous for the minor alleles may be compared to a “weight guard”, which significantly increases the risk of overweight, but not of obesity, because it promotes weight gain only up to the threshold of obesity. Conclusion: The proposed hypothetical effect (“weight guard”) of homozygous for the minor alleles in the TMEM18 based on a rather small sample is a possible explanation of the effects of minor alleles, which minimize the risk of obesity.Iwona Rosset, Dominik Strapagiel, Aneta Sitek, Małgorzata Majewska, Lidia Ostrowska-Nawarycz, Elżbieta Żądzińsk

Association of FTO gene with obesity in Polish schoolchildren

The goal of the study was verification of fat mass and obesity-associated (FTO) gene polymorphisms as significant risk factors of obesity in the population of Polish children. Body mass index (BMI) and DNA were evaluated, where DNA was extracted from saliva, collected from 213 children at the age of 6-13 years. DNA was genotyped by PCR (polymerase chain reaction) and HRM (high resolution melting) techniques, as well as by direct sequencing. Three (3) FTO polymorphisms were identified: rs9939609, rs9926289 and rs76804286, the last polymorphism located between the first two. For the first time, absolute linkage disequilibrium (LD) of FTO gene rs9939609 and rs9926289 polymorphisms was confirmed in data for the Polish population (D’=1, r2=1). The lack of a complete dependence among the three single nucleotide polymorphisms (SNPs) of the FTO gene was a consequence of the concurrence of homozygotes with minor alleles A of rs9939609+rs9926289 of FTO (AA+AA) with major alleles of rs76804286 (GG). A case-control association analysis for BMI in obese children (n=51), as compared to normal-weight children (n=162), was based on the effects of genotypes homozygous for the minor alleles of the studied SNPs in recessive and codominant inheritance models (assuming an independent effect of each genotype). A comparison of children with normal BMI with obese children indicate a strong co-dominant effect of a genotype in homozygotes of minor alleles (AA+AA) of completely linked rs9939609+rs9926289 (OR at age 8.89 ± 1.54 years=4.87, 95% CI 1.81-13.12, p=0.002). An almost five-fold increase of obesity risk in the examined children indicates that the genetic factors, associated with excessive body weight gain, exert stronger effects in the early period of ontogenetic development vs. puberty and adulthood. The role of genetic factors in predisposing to obesity declines with age.Aneta Sitek, Iwona Rosset, Dominik Strapagiel, Małgorzata Majewska, Lidia Ostrowska-Nawarycz, Elżbieta Żądzińsk

Molecular Analysis of Precursor Lesions in Familial Pancreatic Cancer

PMCID: PMC3553106This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Delayed identification and diagnosis of Huntington’s disease due to psychiatric symptoms

Huntington’s disease (HD) is a progressive neurodegenerative illness that affects 2–9/100.000 of the general population. The usual onset is at around age 35–40 years, but there were cases with onset above 55 years. The disease manifests clinically with many neurological and psychiatric symptoms, leading in advanced phases to dementia, but cognitive symptoms are frequently present much earlier in the disease course. HD is caused by an expanded polyglutamine stretch in the N-terminal part of a 350 kDa protein called huntingtin (HTT). This stretch is encoded by a trinucleotide CAG repetition in exon 1 of HTT. An expansion of greater than 36 repeats results in HD. The number of repeats is inversely correlated with the age of onset of motor symptoms, and disease onset during childhood or adolescence is associated with more than 60 CAG repeats. Mood disturbances may be one of the earliest symptoms of HD and may precede the onset of the motor pheno-type for almost 10 years. Neuropsychiatric symptoms may delay the appropriate diagnosis of HD and have major implications for disease management, prognosis and quality of life for patients and families. This case study is about a 58 years old female patient with late identification of Huntington’s disease after two admissions to psychiatric inpatient units, for the treatment of behavioral disturbances

The assessment of cognitive and behavioural disturbances in vascular cognitive impairment (VCI) — recommendations of an expert working group

With newer research-based classification systems, the term Vascular Cognitive Impairment (VCI) is now preferred to vascular dementia. VCI is an umbrella term that includes all forms of cognitive deficits ranging from mild cognitive impairment of vascular origin (VaMCI) to vascular dementia (VaD).The new VCI construct takes into account the fact that in addition to single strategic infarcts, multiple infarcts, and leukoaraiosis, there are other mechanisms of cerebrovascular disease such as chronic hypoperfusion that might account for the pattern of cognitive deficits associated with vascular dementia. The key to defining the spectrum of VCI is neuropsychological testing, bedside or office-based clinical examination, and neuroimaging. The lack of specific cognitive tools that are sufficiently sensitive to detect subtle deficits makes the assessment of cognitive impairment difficult. Prospective cross-sectional and longitudinal studies of VCI from different settings are therefore required.Although there have been few published reports, behavioural and psychological symptoms (BPS) are inherently present in VCI from the onset and during the course of the disease. Besides the type of population (i.e. clinical, community or nursing-home settings), the definition of VCI/VaD and the instruments used, and differences in the prevalence and pattern of BPS between various studies, could be due to other, often unconsidered, factors such as gender, age, education, use of medication and VCI/VaD severity

A polygenic risk score for multiple myeloma risk prediction

There is overwhelming epidemiologic evidence that the risk of multiple myeloma (MM) has a solid genetic background. Genome-wide association studies (GWAS) have identified 23 risk loci that contribute to the genetic susceptibility of MM, but have low individual penetrance. Combining the SNPs in a polygenic risk score (PRS) is a possible approach to improve their usefulness. Using 2361 MM cases and 1415 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium, we computed a weighted and an unweighted PRS. We observed associations with MM risk with OR = 3.44, 95% CI 2.53–4.69, p = 3.55 × 10−15 for the highest vs. lowest quintile of the weighted score, and OR = 3.18, 95% CI 2.1 = 34–4.33, p = 1.62 × 10−13 for the highest vs. lowest quintile of the unweighted score. We found a convincing association of a PRS generated with 23 SNPs and risk of MM. Our work provides additional validation of previously discovered MM risk variants and of their combination into a PRS, which is a first step towards the use of genetics for risk stratification in the general population

Evaluating the role of pathogenic dementia variants in posterior cortical atrophy

Posterior cortical atrophy (PCA) is an understudied visual impairment syndrome most often due to “posterior Alzheimer's disease (AD)” pathology. Case studies detected mutations in PSEN1, PSEN2, GRN, MAPT, and PRNP in subjects with clinical PCA. To detect the frequency and spectrum of mutations in known dementia genes in PCA, we screened 124 European-American subjects with clinical PCA (n = 67) or posterior AD neuropathology (n = 57) for variants in genes implicated in AD, frontotemporal dementia, and prion disease using NeuroX, a customized exome array. Frequencies in PCA of the variants annotated as pathogenic or potentially pathogenic were compared against ∼4300 European-American population controls from the NHLBI Exome Sequencing Project. We identified 2 rare variants not previously reported in PCA, TREM2 Arg47His, and PSEN2 Ser130Leu. No other pathogenic or potentially pathogenic variants were detected in the screened dementia genes. In this first systematic variant screen of a PCA cohort, we report 2 rare mutations in TREM2 and PSEN2, validate our previously reported APOE ε4 association, and demonstrate the utility of NeuroX