Analysis and Design of Tuned Turbo Codes

It has been widely observed that there exists a fundamental trade-off between the minimum (Hamming) distance properties and the iterative decoding convergence behavior of turbo-like codes. While capacity achieving code ensembles typically are asymptotically bad in the sense that their minimum distance does not grow linearly with block length, and they therefore exhibit an error floor at moderate-to-high signal to noise ratios, asymptotically good codes usually converge further away from channel capacity. In this paper, we introduce the concept of tuned turbo codes, a family of asymptotically good hybrid concatenated code ensembles, where asymptotic minimum distance growth rates, convergence thresholds, and code rates can be traded-off using two tuning parameters, {\lambda} and {\mu}. By decreasing {\lambda}, the asymptotic minimum distance growth rate is reduced in exchange for improved iterative decoding convergence behavior, while increasing {\lambda} raises the asymptotic minimum distance growth rate at the expense of worse convergence behavior, and thus the code performance can be tuned to fit the desired application. By decreasing {\mu}, a similar tuning behavior can be achieved for higher rate code ensembles.Comment: Accepted for publication in IEEE Transactions on Information Theor

Evidence for replicative mechanism in a CHD7 rearrangement in a patient with CHARGE syndrome

Haploinsufficiency of CHD7 (OMIM# 608892) is known to cause CHARGE syndrome (OMIM# 214800). Molecular testing supports a definitive diagnosis in approximately 65-70% of cases. Most CHD7 mutations arise de novo, and no mutations affecting exon-7 have been reported to date. We report on an 8-year-old girl diagnosed with CHARGE syndrome that was referred to our laboratory for comprehensive CHD7 gene screening. Genomic DNA from the subject with a suspected diagnosis of CHARGE was isolated from peripheral blood lymphocytes and comprehensive Sanger sequencing, along with deletion/duplication analysis of the CHD7 gene using multiplex ligation-dependent probe amplification (MLPA), was performed. MLPA analysis identified a reduced single probe signal for exon-7 of the CHD7 gene consistent with potential heterozygous deletion. Long-range PCR breakpoint analysis identified a complex genomic rearrangement (CGR) leading to the deletion of exon-7 and breakpoints consistent with a replicative mechanism such as fork stalling and template switching (FoSTeS) or microhomology-mediated break-induced replication (MMBIR). Taken together this represents the first evidence for a CHD7 intragenic CGR in a patient with CHARGE syndrome leading to what appears to be also the first report of a mutation specifically disrupting exon-7. Although likely rare, CGR may represent an overlooked mechanism in subjects with CHARGE syndrome that can be missed by current sequencing and dosage assays

Validation and Utilization of a Clinical Next-Generation Sequencing Panel for Selected Cardiovascular Disorders

The development of high-throughput technologies such as next-generation sequencing (NGS) has allowed for thousands of DNA loci to be interrogated simultaneously in a fast and economical method for the detection of clinically deleterious variants. Whenever a clinical diagnosis is known, a targeted NGS approach involving the use of disease-specific gene panels can be employed. This approach is often valuable as it allows for a more specific and clinically relevant interpretation of results. Here, we describe the customization, validation, and utilization of a commercially available targeted enrichment platform for the scalability of clinical diagnostic cardiovascular genetic tests, including the design of the gene panels, the technical parameters for the quality assurance and quality control, the customization of the bioinformatics pipeline, and the post-bioinformatics analysis procedures. Regions of poor base coverage were detected and targeted by Sanger sequencing as needed. All panels were successfully validated using genotype-known DNA samples either commercially available or from research subjects previously tested in outside clinical laboratories. In our experience, utilizing several of the sub-panels in a clinical setting with 33 real-life cardiovascular patients, we found that 20% of tests requested were reported to have at least one pathogenic or likely pathogenic variant that could explain the patient phenotype. For each of these patients, the positive results may aid the clinical team and the patients in best developing a disease management plan and in identifying relatives at risk

Intragenic CFTR Duplication and 5T/12TG Variant in a Patient with Non-Classic Cystic Fibrosis

Cystic fibrosis (CF) is an autosomal recessive disorder characterized by the accumulation of sticky and heavy mucus that can damage several organs. CF shows variable expressivity in affected individuals, but it typically causes respiratory and digestive complications as well as congenital bilateral absence of the vas deferens in males. Individuals with classic CF usually have variants that produce a defective protein from both alleles of the CFTR gene. Individuals with other variants may present with classic, non-classic, or milder forms of CF due to lower levels of functional CFTR protein. This article reports the genetic analysis of a female with features of asthma and mild or non-classic CF. CFTR sequencing demonstrated that she is a carrier for a maternally derived 5T/12TG variant. Deletion/duplication analysis by multiplex ligation-dependent probe amplification (MLPA) showed the presence of an intragenic paternally derived duplication involving exons 7-11 of the CFTR gene. This duplication is predicted to result in the production of a truncated CFTR protein lacking the terminal part of the nucleotide-binding domain 1 (NBD1) and thus is likely to be a non-functioning allele. The combination of this large intragenic duplication and 5T/12TG is the probable cause of the mild or non-classic CF features in this individual

A Simple Blass Matrix Design Strategy for Multibeam Arbitrary Linear Antenna Arrays

Multibeam antenna arrays are currently recognized as one of the enabling technologies for the next-generation communication standards. One of the key components of these systems is the beamforming network (BFN) that implements the array element excitations. This article addresses this issue by presenting a novel strategy to realize an analog feeding network, which allows an arbitrary linear array (LA) to radiate multiple arbitrary beams. In particular, an iterative procedure is conceived to design a Blass matrix using an identical directional coupler for all nodes, resulting in a very simple structure suitable for large-scale production. Two applications with arbitrary directions are illustrated as proofs-of-concept for the developed architecture: a dual-beam configuration with a null involving an aperiodic LA, and a four-beam configuration involving a periodic LA. For this second application, the effectiveness of the proposed solution is further verified by full-wave simulations and experimental measurements carried out on a fabricated prototype

Genetic mutations in African patients with atrial fibrillation: Rationale and design of the Study of Genetics of Atrial Fibrillation in an African Population (SIGNAL)

BACKGROUND: There is an urgent need to understand genetic associations with atrial fibrillation in ethnically diverse populations. There are no such data from sub-Saharan Africa, despite the fact that atrial fibrillation is one of the fastest growing diseases. Moreover, patients with valvular heart disease are underrepresented in studies of the genetics of atrial fibrillation. METHODS: We designed a case-control study of patients with and without a history of atrial fibrillation in Kenya. Cases with atrial fibrillation included those with and without valvular heart disease. Patients underwent clinical phenotyping and will have laboratory analysis and genetic testing of >240 candidate genes associated with cardiovascular diseases. A 12-month follow-up assessment will determine the groups' morbidity and mortality. The primary analyses will describe genetic and phenotypic associations with atrial fibrillation. RESULTS: We recruited 298 participants: 72 (24%) with nonvalvular atrial fibrillation, 78 (26%) with valvular atrial fibrillation, and 148 (50%) controls without atrial fibrillation. The mean age of cases and controls were 53 and 48 years, respectively. Most (69%) participants were female. Controls more often had hypertension (45%) than did those with valvular atrial fibrillation (27%). Diabetes and current tobacco smoking were uncommon. A history of stroke was present in 25% of cases and in 5% of controls. CONCLUSION: This is the first study determining genetic associations in valvular and nonvalvular atrial fibrillation in sub-Saharan Africa with a control population. The results advance knowledge about atrial fibrillation and will enhance international efforts to decrease atrial fibrillation-related morbidity

The olfactory bulb: an ignored brain structure in the regulation of cardiovascular activity

Numerous studies have addressed the participation of the central nervous system in the physiological regulation of blood pressure and in the development and/or maintenance of hypertension. The central nervous system plays a key role in the short-term regulation of blood pressure although recent investigations also support its participation in the long-term modulation. Diverse brain regions and areas like the rostral ventrolateral medulla, the nucleus of the solitary tract, the locus coeruleus, amygdala and hypothalamus are intimately involved in the control of cardiovascular activity. Nevertheless, little is known about the role of the olfactory bulb. This mini review summarizes current knowledge regarding the participation of this telencephalic region in the regulation of cardiovascular activity in physiological and pathophysiological conditions.Numerosos estudios han abordado la participación del sistema nervioso central en la regulación fisiológica de la presión arterial y en el desarrollo y / o mantenimiento de la hipertensión arterial. El sistema nervioso central juega un papel clave en la regulación a corto plazo de la presión arterial, aunque investigaciones recientes apoyan su participación en la modulación a largo plazo. Diversas regiones y áreas del cerebro como la médula ventrolateral rostral, el núcleo del tracto solitario, el locus coeruleus, la amígdala y el hipotálamo están íntimamente involucradas en el control de la actividad cardiovascular. Sin embargo, poco se conoce acerca del papel del bulbo olfatorio. Esta breve revisión resume el conocimiento actual en la participación de esta región telencefálica en la regulación de la actividad cardiovascular en condiciones fisiológicas y fisiopatológicas.Sociedad Argentina de Fisiologí

Response to comment on "preserved feedforward but impaired top-down processes in the vegetative state".

King et al. raise some technical issues about our recent study showing impaired top-down processes in the vegetative state. We welcome the opportunity to provide more details about our methods and results and to resolve their concerns. We substantiate our interpretation of the results and provide a point-by-point response to the issues raised.Peer reviewe

Distribution of killer cell immunoglobulin-like receptors genes in the Italian Caucasian population

BACKGROUND: Killer cell immunoglobulin-like receptors (KIRs) are a family of inhibitory and activatory receptors that are expressed by most natural killer (NK) cells. The KIR gene family is polymorphic: genomic diversity is achieved through differences in gene content and allelic polymorphism. The number of KIR loci has been reported to vary among individuals, resulting in different KIR haplotypes. In this study we report the genotypic structure of KIRs in 217 unrelated healthy Italian individuals from 22 immunogenetics laboratories, located in the northern, central and southern regions of Italy. METHODS: Two hundred and seventeen DNA samples were studied by a low resolution PCR-SSP kit designed to identify all KIR genes. RESULTS: All 17 KIR genes were observed in the population with different frequencies than other Caucasian and non-Caucasian populations; framework genes KIR3DL3, KIR3DP1, KIR2DL4 and KIR3DL2 were present in all individuals. Sixty-five different profiles were found in this Italian population study. Haplotype A remains the most prevalent and genotype 1, with a frequency of 28.5%, is the most commonly observed in the Italian population. CONCLUSION: The Italian Caucasian population shows polymorphism of the KIR gene family like other Caucasian and non-Caucasian populations. Although 64 genotypes have been observed, genotype 1 remains the most frequent as already observed in other populations. Such knowledge of the KIR gene distribution in populations is very useful in the study of associations with diseases and in selection of donors for haploidentical bone marrow transplantation

Noncompaction of the Ventricular Myocardium Is Associated with a De Novo Mutation in the β-Myosin Heavy Chain Gene

Noncompaction of the ventricular myocardium (NVM) is the morphological hallmark of a rare familial or sporadic unclassified heart disease of heterogeneous origin. NVM results presumably from a congenital developmental error and has been traced back to single point mutations in various genes. The objective of this study was to determine the underlying genetic defect in a large German family suffering from NVM. Twenty four family members were clinically assessed using advanced imaging techniques. For molecular characterization, a genome-wide linkage analysis was undertaken and the disease locus was mapped to chromosome 14ptel-14q12. Subsequently, two genes of the disease interval, MYH6 and MYH7 (encoding the α- and β-myosin heavy chain, respectively) were sequenced, leading to the identification of a previously unknown de novo missense mutation, c.842G>C, in the gene MYH7. The mutation affects a highly conserved amino acid in the myosin subfragment-1 (R281T). In silico simulations suggest that the mutation R281T prevents the formation of a salt bridge between residues R281 and D325, thereby destabilizing the myosin head. The mutation was exclusively present in morphologically affected family members. A few members of the family displayed NVM in combination with other heart defects, such as dislocation of the tricuspid valve (Ebstein's anomaly, EA) and atrial septal defect (ASD). A high degree of clinical variability was observed, ranging from the absence of symptoms in childhood to cardiac death in the third decade of life. The data presented in this report provide first evidence that a mutation in a sarcomeric protein can cause noncompaction of the ventricular myocardium