Search

We define a very general notion of regularity for functions taking values in an alternative real ⁎-algebra. Over Clifford numbers, this notion subsumes the well-established notions of monogenic function and slice-monogenic function. Over quaternions, in addition to subsuming the notions of Fueter-regular function and of slice-regular function, it gives rise to an entirely new theory, which we develop in some detail. [ABSTRACT FROM AUTHOR]

Abstract Background and aims Familial hypercholesterolaemia (FH) is the commonest monogenic disorder that accelerates atherosclerotic cardiovascular disease. We compared and contrasted the characteristics of patients from three specialist centres in the southern hemisphere. Methods Adult index-cases with molecularly diagnosed heterozygous FH attending specialist lipid centres in Cape Town, Perth and São Paulo were studied. Myocardial infarction, revascularisation, hypertension, diabetes, smoking and lipid-lowering treatment were recorded at the time of diagnosis and compared across the three centres. Results The spectrum of genetic variants causative of FH was significantly different in patients attending the centres in South Africa compared with Australia and Brazil. Hypertension and diabetes were more prevalent in Brazilian and Australian patients, than in South African patients, but the frequency of smoking was significantly greater in South Africa than the other two centres (p <0.01). Age, male sex and smoking were significant independent predictors of coronary artery disease (CAD) in all three countries (p <0.05). Conclusions Patients with FH in three specialist centres in the southern hemisphere exhibit a high prevalence of non-cholesterol cardiovascular disease risk factors. Older age, male sex and smoking were more common among subjects with CAD. In all three countries, there should be vigorous programmes for the control of risk factors beyond good control of hypercholesterolaemia among patients with FH. Promotion of a healthy lifestyle, especially anti-smoking advice, is of paramount importance. Highlights • Heterozygous familial hypercholesterolaemia (FH) is the commonest monogenic lipid disorder that accelerates atherosclerotic cardiovascular disease. • Despite differences in genetic variants causing FH, patients attending lipid specialist centres in South Africa, Australia and Brazil have a high prevalence of non-cholesterol risk factors that impact on the risk of coronary artery disease (CAD). • In all three specialist centres, age at diagnosis and current or former smoking were consistent predictors of CAD. This underscores the importance of early treatment of FH patients, as well as counselling against smoking. [ABSTRACT FROM AUTHOR]

Now define S a cartesian product of finite times with S M n which is a finite semigroup having elements { 0 , x , x 2 , … , x n } of order n . Γ( S ) is an undirected graph whose vertices are the nonzero elements of S . It is a new graph type which is the dot product. k be finite positive integer for 0 ≤ { i t } t = 1 k , { j t } t = 1 k ≤ n , any two distinct vertices of S ( x i 1 , x i 2 , … , x i k ) and ( x j 1 , x j 2 , … , x j k ) are adjacent if and only ( x i 1 , x i 2 , … , x i k ) · ( x j 1 , x j 2 , … , x j k ) = 0 S M n (under the dot product) and it is assumed x i t = 0 S M n if i t = 0 . In this study, the value of diameter, girth, maximum and minimum degrees, domination number, clique and chromatic numbers and in parallel with perfectness of Γ( S ) are elucidated. [ABSTRACT FROM AUTHOR]

In this paper, we introduce and study a Bargmann–Radon transform on the real monogenic Bargmann module. This transform is defined as the projection of the real Bargmann module on the closed submodule of monogenic functions spanned by the monogenic plane waves. We prove that this projection can be written in integral form in terms the so-called Bargmann–Radon kernel. Moreover, we have a characterization formula for the Bargmann–Radon transform of a function in the real Bargmann module in terms of its complex extension and then its restriction to the nullcone in C m . We also show that the formula holds for the Szegő–Radon transform that we introduced in Colombo et al. (2016) and we define the dual transform and we provide an inversion formula. Finally, in Theorem 5.6, we prove an integral formula for the monogenic part of an entire function. [ABSTRACT FROM AUTHOR]

Thanks to considerable progresses made over the last 30 years, hemophilia benefits from the most efficacious and safe treatment among the many monogenic inherited disorders. The most challenging complication of replacement therapy in hemophilia A is the occurrence of alloantibodies against infused factor VIII (FVIII), thus predisposing the patients to increased morbidity and disability. Extensive research in this field has definitively unraveled that development of inhibitors in hemophilia A is a complex and multifactorial process, in which inherited and environmental factors dynamically interact. This narrative review, after providing a concise overview about the main genetic and non-genetic risk factors, is aimed to focus on prediction risk models and preventive strategies for minimizing the risk of developing inhibitors in hemophilia A patients. [ABSTRACT FROM AUTHOR]

Presenilin 1 ( PSEN1 ) mutations are the main cause of monogenic Alzheimer's disease. We studied the functional effects of the mutation K239N, which shows incomplete penetrance at the age of 65 years and compared it with the more aggressive mutation E120G. We engineered stable cell lines expressing human PSEN1 wild type or with K239N or E120G mutations. Both mutations induced dysfunction of γ-secretase in the processing of amyloid-β protein precursor, leading to an increase in the amyloid β 42 /amyloid β 40 ratio. Analysis of homeostatic mechanisms showed that K239N induced lower basal and hydrogen peroxide induced intracellular levels of reactive oxygen species than E120G. Similarly, K239N induced lower vulnerability to apoptosis by hydrogen peroxide injury than E120G. Accordingly, the proapoptotic signaling pathways c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase maintained PSEN1-mediated negative regulation in K239N but not in E120G-bearing cells. Furthermore, the activation of the prosurvival signaling pathways mitogen-activated protein kinase/extracellular signal-regulated kinase and phosphoinositide 3-kinase/Akt was lower in E120G-bearing cells. Therefore, preservation of mechanisms regulating cell responses independent of amyloid-β protein precursor processing may account for the milder phenotype induced by the PSEN1 K239N mutation. [ABSTRACT FROM AUTHOR]

The well known Fueter theorem allows to construct quaternionic regular functions or monogenic functions with values in a Clifford algebra defined on open sets of Euclidean space R n + 1 , starting from a holomorphic function in one complex variable or, more in general, from a slice hyperholomorphic function. Recently, the inversion of this theorem has been obtained for odd values of the dimension n . The present work extends the result to all dimensions n by using the Fourier multiplier method. More precisely, we show that for any axially monogenic function f defined in a suitable open set in R n + 1 , where n is a positive integer, we can find a slice hyperholomorphic function f → such that f = Δ ( n − 1 ) / 2 f → . Both the even and the odd dimensions are treated with the same, viz., the Fourier multiplier, method. For the odd dimensional cases the result obtained by the Fourier multiplier method coincides with the existing result obtained through the pointwise differential method. [ABSTRACT FROM AUTHOR]

In this paper, we introduce a Somigliana formula in quaternion analysis. Solutions of the Lamé–Navier system in the forms of the Grigor'ev solution, the Papkovich–Neuber solution and the Ter-Mkrtychan–Naghdi–Hsu solution are included in this Somigliana formula. In application, a new generalized Kolosov–Muskhelishvili formula is constructed. • A new Somigliana formula in quaternion analysis. • In connection with the Grigor'ev solution, the Papkovich–Neuber solution and the Ter-Mkrtychan–Naghdi–Hsu solution. • A new generalized Kolosov–Muskhelishvili formulae in the three-dimensional linear elasticity. • Using two monogenic functions in quaternion analysis in arbitrary bounded domains with smooth boundary. [ABSTRACT FROM AUTHOR]

The Laplace and Dirac operators are rotation invariant operators which can be neatly expressed in (continuous) Euclidean Clifford analysis. In this paper, we consider the discrete counterparts of these operators, i.e. the discrete Laplacian Δ or star-Laplacian and the discrete Dirac operator ∂. We explicitly construct rotations operators for both of these differential operators (denoted by Ω a, b and dR ( e a, b ) respectively) in the discrete Clifford analysis setting. The operators Ω a, b satisfy the defining relations for so ( m , C ) and they are endomorphisms of the space H k of k -homogeneous (discrete) harmonic polynomials, hence expressing H k as a finite-dimensional so ( m , C ) -representation. Furthermore, the space M k of (discrete) k -homogeneous monogenic polynomials can likewise be expressed as so ( m , C ) -representation by means of the operators dR ( e a, b ). We will also consider rotations of discrete harmonic (resp. monogenic) distributions, in particular point-distributions, which will allow us to evaluate functions in a rotated point. To make the discrete rotations more visual, we explicitly calculate the rotation of general point-distributions in two dimensions, showing the behavior of such discrete rotations in relation to the continuous case. [ABSTRACT FROM AUTHOR]

Aims: Neonatal diabetes mellitus (NDM) is a rare monogenic disorder, reported to affect less than 2 cases per 100,000 infants. There are two types, permanent (PNDM) and transient (TNDM). We describe our clinical experience in determining and comparing the genetic basis of diabetes in children with onset before 6months versus those diagnosed between 6 and 12months of age.Methods: We reviewed medical records of children with diabetes diagnosed before 12months of age. Genetic testing was performed in all cases.Results: 12 patients were diagnosed with diabetes before 6months of age (PNDM=6; TNDM=6), and 11 patients between 6 and 12months (all with permanent diabetes). Among children with PNDM, we identified three different KCNJ11 mutations in 5 patients, and one novel ABCC8 mutation in a single patient. Among children with TNDM, we detected a KCNJ11 and ABCC8 mutation each in a single patient and methylation abnormalities at chromosome 6q24 in 4 patients. Among children with diabetes diagnosed between 6 and 12months, 1 patient had an INS mutation and one patient was homozygous for an SLC19A2 mutation which confirmed a diagnosis of thiamine-responsive megaloblastic anaemia syndrome. Five of the patients with an ABCC8 or KCNJ11 mutation have successfully transferred from insulin to glibenclamide whist 1 child demonstrated a partial response to sulfonylurea treatment.Conclusions: Investigating the underlying genetic basis of diabetes in children with onset before 1year is useful for choosing the most efficient treatment, the basis of Personalized Medicine. [ABSTRACT FROM AUTHOR]

The formation of a properly shaped eye is a complex developmental event that requires the coordination of many induction processes and differentiation pathways. Microphthalmia and anophthalmia (MA) represent the most severe defects that can affect the ocular globe during embryonic development. When genetic, these ocular disorders exhibit large genetic heterogeneity and extreme variable expressivity. Around 20 monogenic diseases are known to be associated with MA as main phenotype and the penetrance of mutations is usually full in the patients. Some of these genes encode proteins involved in the vitamin A pathway, tightly regulated during eye development. One of those retinoic acid synthesis genes is ALDH1A3 and biallelic mutations in that gene have been recently found to lead to MA phenotype in patients. Interestingly, we report here the lack of ocular defect in a girl carrying the same homozygous mutation in the ALDH1A3 gene than the affected members of her family. Thus, this report brings new information for the phenotype–genotype correlation of ALDH1A3 mutations and raises important questions, especially in terms of genetic counselling given to the patients and their families. Furthermore, these data contribute to the more general understanding that we have for the complex genetic inheritance of these MA phenotypes. [ABSTRACT FROM AUTHOR]

A shelf is a set with a binary operation ▹ satisfying a ▹ ( b ▹ c ) = ( a ▹ b ) ▹ ( a ▹ c ) . Racks are shelves with invertible translations b ↦ a ▹ b ; many of their aspects, including cohomological, are better understood than those of general shelves. Finite monogenic shelves (FMS), of which Laver tables and cyclic racks are the most famous examples, form a remarkably rich family of structures and play an important role in set theory. We compute the cohomology of FMS with arbitrary coefficients. On the way we develop general tools for studying the cohomology of shelves. Moreover, inside any finite shelf we identify a sub-rack which inherits its major characteristics, including the cohomology. For FMS, these sub-racks are all cyclic. [ABSTRACT FROM AUTHOR]

Fuelled by the on-going sequencing revolution, the last two years have seen a number of exciting discoveries relating to monogenic disorders predisposing to autoimmunity that provide new insights into the function of the human immune system. Here we discuss a selection of these diseases due to mutations in PRKCD , CTLA4 , STAT3 , IFIH1 , TMEM173 and COPA . [ABSTRACT FROM AUTHOR]

In this note we consider certain jump problem for poly-monogenic functions in fractal domains with higher order Lipschitz boundary data. This is accomplished by using a higher order Teodorescu operator which replaces the expected surface integral. Also, we give out the uniqueness of solutions basing the work on the method of removable singularities for monogenic functions making use of a Dolzhenko type theorem. [ABSTRACT FROM AUTHOR]

Objective The contribution of genetic causes to Parkinson's disease (PD) is strongest in early-onset cases. We ascertained a nationwide cohort of patients in order to study the genetic epidemiology of early-onset PD (EOPD) in Finland. Methods By means of a search in a national database we ascertained all patients with EOPD. These patients had become eligible for reimbursement of PD drugs between the years 1995–2006 and were <55 years of age at the time of PD diagnosis. A total of 441 patients consented and provided clinical and genealogical information. Results The incidence of EOPD increased 1.7-fold between the years 1995–2006, the mean annual incidence being 3.3/100,000. Fifty-two patients (11.8%) reported an affected first-degree relative. The birthplaces of patients with PD among first-degree relatives were clustered in certain regions in the southwestern and western coastal provinces of Finland and in the eastern province of Savo. Furthermore, the distance between the birthplaces of the patients' parents was smaller for patients, who had first-degree relatives with PD than for patients with no family history of PD. Conclusions Our data suggest that the incidence of EOPD is increasing. The birthplaces of patients with PD among first-degree relatives were clustered in certain provinces of Finland suggesting that monogenic forms of PD or genetic susceptibility of PD are present in the population. [ABSTRACT FROM AUTHOR]

A previous report suggested that 88% of individuals in the general population with total cholesterol (TC) > 9.3 mmol/L have familial hypercholesterolaemia (FH). We tested this hypothesis in a cohort of 4896 UK civil servants, mean (SD) age 44 (±6) years, using next generation sequencing to achieve a comprehensive genetic diagnosis. 25 (0.5%) participants (mean age 49.2 years) had baseline TC > 9.3 mmol/L, and overall we found an FH-causing mutation in the LDLR gene in seven (28%) subjects. The detection rate increased to 39% by excluding eight participants with triglyceride levels over 2.3 mmol/L, and reached 75% in those with TC > 10.4 mmol/L. By extrapolation, the detection rate would be ∼25% by including all participants with TC > 8.6 mmol/L (2.5 standard deviations from the mean). Based on the 1/500 FH frequency, 30% of all FH-cases in this cohort would be missed using the 9.3 mmol/L cut-off. Given that an overall detection rate of 25% is considered economically acceptable, these data suggest that a diagnostic TC cut-off of 8.6 mmol/L, rather than 9.3 mmol/L would be clinically useful for FH in the general population. [ABSTRACT FROM AUTHOR]

A conformal mapping in a plane domain locally maps circles to circles. More generally, quasiconformal mappings locally map circles to ellipses of bounded distortion. In this work, we study the corresponding situation for solutions to Stein–Weiss systems in the ( n + 1 ) D Euclidean space. This class of solutions is a transformation of a subset of monogenic locally quasiconformal mappings with nonvanishing Jacobian. In the theoretical part of this work, we prove that an M-conformal mapping locally maps the unit hypersphere onto explicitly characterized hyperellipsoids and vice versa. Then we discuss quasiconformal radial mappings and their relations with the Cauchy kernel and p -monogenic mappings. This is followed by the consideration of quadratic M-conformal mappings. In the applications part of this work, we provide the reader with some plot examples that demonstrate the effectiveness of our approach. [ABSTRACT FROM AUTHOR]

One of the most fruitful and elegant approach (known as Kolosov-Muskhelishvili formulas) for plane isotropic elastic problems is to use two complex-valued holomorphic potentials. In this paper, the algebra of real quaternions is used in order to propose in three dimensions, an extension of the classical Muskhelishvili formulas. The starting point is the classical harmonic potential representation due to Papkovich and Neuber. Alike the classical complex formulation, two monogenic functions very similar to holomorphic functions in 2D and conserving many of interesting properties, are used in this contribution. The completeness of the potential formulation is demonstrated rigorously. Moreover, body forces, residual stress and thermal strain are taken into account as a left side term. The obtained monogenic representation is compact and a straightforward calculation shows that classical complex representation for plane problems is embedded in the presented extended formulas. Finally the classical uniqueness problem of the Papkovich-Neuber solutions is overcome for polynomial solutions by fixing explicitly linear dependencies. [ABSTRACT FROM AUTHOR]

Fragile X syndrome (FXS) is a monogenic disease caused by mutations in the FMR1 gene. The Fmr1 knockout (KO) mice show many aspects of FXS-related phenotypes, and have been used as a major pre-clinical model for FXS. Although FXS occurs in both male and female patients, most studies on the mouse model use male animals. Few studies test whether gender affects the face validity of the mouse model. Here, we examined multiple behavioral phenotypes with male hemizygous and female homozygous Fmr1 KO mice on C57BL/6 background. For each behavioral paradigm, we examined multiple cohorts from different litters. We found that both male and female Fmr1 KO mice displayed significant audiogenic seizures, hyperactivity in the open field test, deficits in passive avoidance and contextual fear memory, and significant enhancement of PPI at low stimulus intensity. Male and female Fmr1 KO mice also showed more transitional movement between the lit and dark chambers in the light-dark tests. The lack of gender effects suggests that the Fmr1 KO mouse is a reasonable tool to test the efficacy of potential FXS therapies. [ABSTRACT FROM AUTHOR]

Abstract: In Das et al. (2013) [8], a new graph on monogenic semigroups (with zero) having elements has been recently defined. The vertices are the non-zero elements and, for , any two distinct vertices and are adjacent if in . As a continuing study, in Akgunes et al. (2014) [3], it has been investigated some well known indices (first Zagreb index, second Zagreb index, Randić index, geometric–arithmetic index, atom-bond connectivity index, Wiener index, Harary index, first and second Zagreb eccentricity indices, eccentric connectivity index, the degree distance) over . In the light of above references, our main aim in this paper is to extend these studies over to the tensor product. In detail, we will investigate the diameter, radius, girth, maximum and minimum degree, chromatic number, clique number and domination number for the tensor product of any two (not necessarily different) graphs and . [Copyright &y& Elsevier]

Abstract: Objective: Monogenic congenital cataract is one of the most genetically heterogeneous ocular conditions with almost 30 different genes involved in its etiology. In adult patients, genotype–phenotype correlations are troubled by eye surgery during infancy and/or long-term ocular complications. Here, we describe the molecular diagnosis of GALK1 deficiency as the cause of autosomal recessive congenital cataract in a family from Costa Rica. Methods: Four affected siblings were included in the study. All of them underwent eye surgery during the first decade but medical records were not available. Congenital cataract was diagnosed by report. Molecular analysis included genome wide homozygosity mapping using a 250K SNP Affymetrix microarray followed by PCR amplification and direct nucleotide sequencing of candidate gene. Results: Genome wide homozygosity mapping revealed a 6Mb region of homozygosity shared by two affected siblings at 17q25. The GALK1 gene was included in this interval and direct sequencing of this gene revealed a homozygous c.1144C>T mutation (p.Q382*) in all four affected subjects. Conclusions: This work demonstrates the utility of homozygosity mapping in the retrospective diagnosis of a family with congenital cataracts in which ocular surgery at early age, the lack of medical records, and the presence of long term eye complications, impeded a clear clinical diagnosis during the initial phases of evaluation. [Copyright &y& Elsevier]

Abstract: Autism is the short name of a complex and heterogeneous group of disorders (autism spectrum disorders, ASD) with several lead symptoms required for classification, including compromised social interaction, reduced verbal communication and stereotyped repetitive behaviors/restricted interests. The etiology of ASD is still unknown in most cases but monogenic heritable forms exist that have provided insights into ASD pathogenesis and have led to the notion of autism as a ‘synapse disorder’. Among the most frequent monogenic causes of autism are loss-of-function mutations of the NLGN4X gene which encodes the synaptic cell adhesion protein neuroligin-4X (NLGN4X). We previously described autism-like behaviors in male Nlgn4 null mutant mice, including reduced social interaction and ultrasonic communication. Here, we extend the phenotypical characterization of Nlgn4 null mutant mice to both genders and add a series of additional autism-relevant behavioral readouts. We now report similar social interaction and ultrasonic communication deficits in females as in males. Furthermore, aggression, nest-building parameters, as well as self-grooming and circling as indicators of repetitive behaviors/stereotypies were explored in both genders. The construction of a gender-specific autism severity composite score for Nlgn4 mutant mice markedly diminishes population/sample heterogeneity typically obtained for single tests, resulting in p values of <0.00001 and a genotype predictability of 100% for male and of >83% for female mice. Taken together, these data underscore the similarity of phenotypical consequences of Nlgn4/NLGN4X loss-of-function in mouse and man, and emphasize the high relevance of Nlgn4 null mutant mice as an ASD model with both construct and face validity. [Copyright &y& Elsevier]

The Hua-Radon and polarized Hua-Radon transform are two orthogonal projections defined on holomorphic functions in the Lie sphere. Both transformations can be written as integral transforms with respect to a suitable reproducing kernel. Integrating both kernels over a Stiefel manifold yields a linear combination of zonal spherical monogenics. Using an Almansi type decomposition of holomorphic functions and reproducing properties of the zonal monogenics, we obtain an inversion formula for both the Hua-Radon and the polarized Hua-Radon transform. [ABSTRACT FROM AUTHOR]

In this paper, we study a refinement of the Szegö-Radon transform in the hypermonogenic setting. Hypermonogenic functions form a subclass of monogenic functions arising in the study of a modified Dirac operator, which allows for weaker symmetries and also has a strong connection to the hyperbolic metric. In particular, we construct a projection operator from a module of hypermonogenic functions in R p + q onto a suitable submodule of plane waves parameterized by a vector on the unit sphere of R q. Moreover, we study the interaction of this Szegö-Radon transform with the generalized Cauchy-Kovalevskaya extension operator. Finally, we develop a reconstruction (inversion) method for this transform. [ABSTRACT FROM AUTHOR]

Abstract: Since the identification of LRP5 as the causative gene for the osteoporosis pseudoglioma syndrome (OPPG) as well as the high bone mass (HBM) phenotype, LRP5 and the Wnt/β-catenin signaling have been extensively studied for their role in the differentiation and proliferation of osteoblasts, in the apoptosis of osteoblasts and osteocytes and in the response of bone to mechanical loading. However, more recently the direct effect of LRP5 on osteoblasts and bone formation has been questioned. Gene expression studies showed that mice lacking lrp5 have increased expression of tph1, the rate limiting enzyme for the production of serotonin in the gut. Furthermore mice lacking either tph1 or htr1B, the receptor for serotonin on the osteoblasts, were reported to have an increased bone mass due to increased bone formation. This led to the still controversial hypothesis that LRP5 influences bone formation indirectly by regulating the expression of thp1 and as a consequence influencing the production of serotonin in the gut. Based on these data we decided to evaluate the role of TPH1 and HTR1B in the development of craniotubular hyperostoses, a group of monogenic sclerosing bone dysplasias. We screened the coding regions of both genes in 53 patients lacking a mutation in the known causative genes LRP5, LRP4 and SOST. We could not find disease-causing coding variants in neither of the tested genes and therefore, we cannot provide support for an important function of TPH1 and HTR1B in the pathogenesis of sclerosing bone dysplasias in our tested patient cohort. [Copyright &y& Elsevier]

Highlights: [•] We summarize the mitochondrial respiratory chain defects and mtDNA mutations that are affected in PD. [•] We outline the effects of environmental toxins on mitochondrial function in PD. [•] We narrate the mitochondrial dysfunction associated with monogenic PD. [ABSTRACT FROM AUTHOR]

Abstract: There is a strong association between lysosome enzyme deficiencies and monogenic disorders resulting in lysosomal storage disease. Of the more than 75 characterized lysosomal proteins, two thirds are directly linked to inherited diseases of metabolism. Only one lysosomal storage disease, Niemann–Pick disease, is associated with impaired phospholipid metabolism. However, other phospholipases are found in the lysosome but remain poorly characterized. A recent exception is lysosomal phospholipase A2 (group XV phospholipase A2). Although no inherited disorder of lysosomal phospholipid metabolism has yet been associated with a loss of function of this lipase, this enzyme may be a target for an acquired form of lysosomal storage, drug induced phospholipidosis. This article is part of a Special Issue entitled Phospholipids and Phospholipid Metabolism. [Copyright &y& Elsevier]

Abstract: Monogenic orthogonal polynomials over 3D prolate spheroids were previously introduced and shown to have some remarkable properties. In particular, the underlying functions take values in the quaternions (identified with ), and are generally assumed to be nullsolutions of the well known Moisil–Théodoresco system. In this paper, we show that these polynomial functions play an important role in defining the Szegö kernel function over the surface of 3D (prolate) spheroids. As a concrete application, we prove an explicit expression of the monogenic Szegö kernel function over 3D (prolate) spheroids and present two numerical examples. [Copyright &y& Elsevier]

Abstract: The object of this paper is to construct a complete orthogonal system of monogenic polynomials as solutions of the Moisil–Théodoresco system over prolate spheroids in . This will be done in the spaces of square integrable functions over . A big breakthrough is that the orthogonality of the polynomials in question does not depend on the shape of the spheroids, but only on the location of the foci of the ellipse generating the spheroid. The representations of these polynomials are given explicitly, ready to be implemented on a computer. In addition, we show a corresponding orthogonality of the same polynomials over the surface of the spheroids with respect to a suitable weight function. [Copyright &y& Elsevier]

Abstract: An attempt has been made to give some criteria (Criteria II) for a function defined in the space of analytic functions to be univalent. Such criteria extend those obtained earlier from Ahlfors-type univalence criteria of analytic functions. We also discuss its application in the space of analytic functions. [Copyright &y& Elsevier]

Abstract: Background: Genetic factors regulate both high-density lipoprotein (HDL) levels and functionality, thus affecting HDL antiatherogenic properties. We characterized the HDL antioxidant/anti-inflammatory properties and apoA-I-containing subpopulations in families with monogenic low HDL disorders. Methods: Subjects with mutations in apolipoprotein A-I (apoA-I), ATP-binding cassette transporter A1 (ABCA1) or lecithin:cholesterol acyltransferase (LCAT) and family controls were studied. HDL antioxidant/anti-inflammatory properties were assayed by an in vitro fluorometric method and HDL-associated paraoxonase-1 (PON1), platelet activating factor-acetylhydrolase (PAF-AH), LCAT, malondialdehyde (MDA), PAF and serum amyloid A (SAA) were measured. ApoA-I-containing HDL subpopulations were analyzed by two-dimensional non-denaturing gel electrophoresis. Results: ApoA-I heterozygotes and subjects with partial or complete ABCA1 or LCAT deficiency had HDL with reduced antioxidant/anti-inflammatory properties and increased MDA levels. HDL-PON1 activity was reduced in apoA-I heterozygotes and in subjects with complete ABCA1 deficiency. HDL-PAF-AH activity was reduced in subjects with partial or complete ABCA1 deficiency or complete LCAT deficiency. HDL-LCAT activity was reduced in all LCAT mutation carriers. HDL-PAF levels were increased in apoA-I heterozygotes. HDL-SAA levels were increased in subjects with complete ABCA1 deficiency. ApoA-I, ABCA1 and LCAT heterozygotes were depleted of the large α1 HDL subpopulation. Subjects with complete LCAT deficiency showed mostly the small α4 HDL subpopulation and subjects with complete ABCA1 deficiency the α4 and preβ HDL subpopulations. Conclusions: This study shows that mutations in apoA-I, ABCA1 and LCAT have direct effect on the antioxidant/anti-inflammatory properties of HDL. Furthermore, our study shows the effect of specific mutations on the apoA-I-containing HDL subpopulation profiles. [Copyright &y& Elsevier]

Congestive heart failure is a major cause of morbidity and mortality in the United States. Although progress in conventional treatments is making steady and incremental gains to decrease heart failure mortality, there is a critical need to explore new therapeutic approaches. Gene therapy was initially applied in the clinical setting for inherited monogenic disorders. It is now apparent that gene therapy has broader potential that also includes acquired polygenic diseases, such as congestive heart failure. Recent advances in understanding of the molecular basis of myocardial dysfunction, together with the evolution of increasingly efficient gene transfer technology, have placed heart failure within the reach of gene-based therapy. Furthermore, the recent successful and safe completion of a phase 2 trial targeting the sarcoplasmic reticulum Ca2+ ATPase pump along with the start of more recent phase 1 trials are ushering in a new era of gene therapy for the treatment of heart failure. [ABSTRACT FROM AUTHOR]

Abstract: Hypercomplex function theory generalizes the theory of holomorphic functions of one complex variable by using Clifford Algebras and provides the fundamentals of Clifford Analysis as a refinement of Harmonic Analysis in higher dimensions. We define the Laguerre derivative operator in hypercomplex context and by using operational techniques we construct generalized hypercomplex monogenic Laguerre polynomials. Moreover, Laguerre-type exponentials of order are defined. [ABSTRACT FROM AUTHOR]

Abstract: Compared to the successful probing of genetic causes of monogenic disorders, dissecting the genetics of complex polygenic diseases has until recently been a fairly slow and cumbersome process. With the introduction of whole genome wide association studies (WGAS) the situation dramatically changed in 2007. The results from several recent WGAS on type 2 diabetes (T2D) and obesity have identified at least eighteen genes consistently associated with T2D. Many of the genes implicate pancreatic beta-cell function in the pathogenesis of T2D whereas only one clearly associate with insulin resistance. The identified genes most likely merely represent the tip of the iceberg in the explanation behind T2D. Refined tools will have to provide a more complete picture of the genetic complexity of T2D over the next few years. In addition to common variants increasing susceptibility for the disease, rare variants with stronger effects, copy number variations, and epigenetic effects like DNA methylation and histone acetylation will become important. Nevertheless, today we are able for the first time to anticipate that the genetics of a complex disease like T2D really can be dissected. [Copyright &y& Elsevier]

A key feature of the immune system is the capacity to monitor and control infections from non-self pathogens while maintaining tolerance to self-antigens. Primary immunodeficiencies (PID) are characterized by an increased susceptibility to infections, often associated with aberrant inflammatory responses and a concomitant high prevalence of autoimmunity. Autoimmunity in PID raises a conundrum: How can an immune system fail to respond to non-self pathogens while reacting vigorously to self-antigens? Recent advances from studies of PID patients and related animal models have revealed the crucial role of Aire-induced expression of self-antigens for deletion of autoreactive T cells in the thymus (central tolerance). Moreover, lessons from PID have provided unequivocal evidence for the essential role of regulatory T cells in suppressing autoreactive T cells in the periphery. Finally, findings from PID have broadened our understanding of how homeostatic proliferation and increased load or decreased clearance of apoptotic cells and non-self pathogens can lead to breakdown of peripheral tolerance. [Copyright &y& Elsevier]

Abstract: To achieve a decision with which the group is satisfied, the group members must accept the judgments, and ultimately the priorities. This requires that (a) the judgments be homogeneous, and (b) the priorities of the individual group members be compatible with the group priorities. There are three levels on which the homogeneity of group preference needs to be considered: (1) for a single paired comparison (monogeneity), (2) for an entire matrix of paired comparisons (multigeneity), and (3) for a hierarchy or network (omnigeneity). In this paper we study monogeneity and the impact it has on group priorities. [Copyright &y& Elsevier]

In this paper, it is shown that certain classes of special monogenic functions cannot be represented by the basic series in the whole space. New definitions for the order of basis of special monogenic polynomials are given together with theorems on representation of classes of special monogenic functions in certain balls and at a point. [Copyright &y& Elsevier]

We show that if A1,A2,…,An,B1,B2,…,Bt are uniform objects of an abelian category C, then A1⊕A2⊕⋯⊕An and B1⊕B2⊕⋯⊕Bt are in the same monogeny class if and only if n=t and there is a permutation σ of {1,2,…,n} such that Ai and Bσ(i) are in the same monogeny class for every i=1,2,…,n. This is proved by showing that strong components of bipartite digraphs with enough edges intersect the two independent sets of vertices of a bipartition of the digraph in sets of the same cardinality. [Copyright &y& Elsevier]

Abstract: Multiple sclerosis is not known to be a risk factor for subsequent development of cancer. Recently, a multiple sclerosis locus was mapped adjacent to BRCA1 gene. We present a familial case affected by multiple sclerosis and cancer. We identified a c.5266dupC (5382insC) frameshift mutation in a 33-year-old woman with breast cancer, multiple malignant melanomas and multiple sclerosis. The patient's family history shows further cases of multiple sclerosis in BRCA1 mutation carriers. Therefore the presented family may carry a monogenic predisposition for multiple sclerosis nearby to BRCA1. [Copyright &y& Elsevier]

A contragenic function in a domain Ω ⊆ R 3 is a reduced-quaternion valued (i.e the last quaternionic coordinate is zero) harmonic function, which is orthogonal in L 2(Ω) to all reduced-quaternion monogenic functions and their conjugates. Contragenicity is not a local property. For spheroidal domains of arbitrary eccentricity, we relate standard orthogonal bases of harmonic and contragenic functions for one spheroid to another via computational formulas. This permits us to show that there exist nontrivial contragenic functions common to the spheroids of all eccentricities. [ABSTRACT FROM AUTHOR]

The author reflects on treatments for different genetic diseases. He mentions that 2014 brings with it new genetic tools, which include the potential for site-specific viral vector integration that will have significant effect on treating monogenic diseases. He states that to obtain the goal as specific vector integration needs diverse technologies combination, a feat can be accomplished in commercial environment instead of academic.

The muscular dystrophies are a clinically and histologically well characterized group of genetic diseases, with predominantly monogenic etiologies. Many causative gene mutations have been already identified, but the underlying pathophysiological pathways and phenotypic variability in each form are much more complex, suggesting the involvement of many other genes. Thus, study the whole genome expression profile can significantly contribute to: identify altered biological functions which could contribute to the understanding of the disease; identify possible prognostic biomarkers and find points for therapeutic intervention. Here, we present the first global gene expression analysis of the muscle of MD mouse models: Large myd (CMD1D), Dmd mdx /Large myd (double mutant for DMD and CMD1D) compared to Dmd mdx (model for Duchenne MD) and normal C57BL , in three different ages: 21 days, 3 and 6 months. Five animals from each group were analyzed using DNA microarrays. The data were preprocessed and normalized in Expression Console software and screening of DEGs was done with SAM method. In general, a predominance of upregulated than downregulated genes was observed in the dystrophic muscles, compatible with high rates of protein turnover that could occur due to the subsequent activation of regeneration process. The Large myd and Dmd mdx /Large myd mice present a progressive increase in the number of differentially expressed genes (DEGs) with aging. The analysis done between Dmd mdx / Large myd and its parental lineages Dmd mdx and Large myd showed the smallest number of DEGs, suggesting that the reason of its worst phenotype is controlled by the expression of a few but very important genes. Preliminary functional analyses in IPA and Expander softwares showed a high proportion of genes involved in immune and inflammatory pathways in all lineages that could be explained by the intense dystrophic process. [ABSTRACT FROM AUTHOR]

Summary: Primary monogenic forms of dystonia manifest solely or mainly with dystonia; they have been linked to a number of genes and loci and assigned “DYT” numbers. The pure dystonia syndrome early-onset primary dystonia (DYT1) manifests with dominantly-inherited generalized dystonia, often with focal onset in a limb. DYT1 is caused by a GAG deletion in the TOR1A gene. Mutations in the THAP1 gene cause DYT6, a form of pure dystonia that primarily involves cranio-cervical and upper limb muscles. Patients with the dystonia plus syndrome DYT5 display levodopa-responsive dystonia sometimes associated with tremor or parkinsonism (DYT5a, mutations in GCH1); a more severe phenotype with psychomotor involvement can be seen in recessive forms (DYT5b with TH mutations, SPR-deficiency syndrome). Other forms of dystonia plus syndromes include myoclonic dystonia (DYT11) and rapid-onset dystonia-parkinsonism (DYT12). Finally, paroxysmal exertion-induced dystonia (DYT18, GLUT1 deficiency) is caused by mutations in the SLC2A1 gene (DYT9 and DYT18). It is part of the paroxysmal dystonia group and manifests with paroxystic movements sometimes associated with seizures and psychomotor developmental delay. [Copyright &y& Elsevier]