Systematic Analysis of Gene Expression Differences between Left and Right Atria in Different Mouse Strains and in Human Atrial Tissue

Background: Normal development of the atria requires left-right differentiation during embryonic development. Reduced expression of Pitx2c (paired-like homeodomain transcription factor 2, isoform c), a key regulator of left-right asymmetry, has recently been linked to atrial fibrillation. We therefore systematically studied the molecular composition of left and right atrial tissue in adult murine and human atria. Methods: We compared left and right atrial gene expression in healthy, adult mice of different strains and ages by employing whole genome array analyses on freshly frozen atrial tissue. Selected genes with enriched expression in either atrium were validated by RT-qPCR and Western blot in further animals and in shock-frozen left and right atrial appendages of patients undergoing open heart surgery. Results: We identified 77 genes with preferential expression in one atrium that were common in all strains and age groups analysed. Independent of strain and age, Pitx2c was the gene with the highest enrichment in left atrium, while Bmp10, a member of the TGFb family, showed highest enrichment in right atrium. These differences were validated by RT-qPCR in murine and human tissue. Western blot showed a 2-fold left-right concentration gradient in PITX2 protein in adult human atria. Several of the genes and gene groups enriched in left atria have a known biological role for maintenance of healthy physiology, specifically the prevention of atrial pathologies involved in atrial fibrillation, including membrane electrophysiology, metabolic cellular function, and regulation of inflammatory processes. Comparison of the array datasets with published array analyses in heterozygous Pitx2c+/2 atria suggested that approximately half of the genes with left-sided enrichment are regulated by Pitx2c. Conclusions: Our study reveals systematic differences between left and right atrial gene expression and supports the hypothesis that Pitx2c has a functional role in maintaining ‘‘leftness’’ in the atrium in adult murine and human hearts

Correlates of genetic monogamy in socially monogamous mammals: insights from Azara's owl monkeys

Understanding the evolution of mating systems, a central topic in evolutionary biology for more than 50 years, requires examining the genetic consequences of mating and the relationships between social systems and mating systems. Among pair-living mammals, where genetic monogamy is extremely rare, the extent of extra-group paternity rates has been associated withmale participation in infant care, strength of the pair bond and length of the breeding season. This study evaluated the relationship between two of those factors and the genetic mating system of socially monogamous mammals, testing predictions that male care and strength of pair bond would be negatively correlated with rates of extra-pair paternity (EPP). Autosomal microsatellite analyses provide evidence for genetic monogamy in a pair-living primate with bi-parental care, the Azara’s owl monkey (Aotus azarae). A phylogenetically corrected generalized least square analysis was used to relate male care and strength of the pair bond to their genetic mating system (i.e. proportions of EPP) in 15 socially monogamous mammalian species. The intensity of male care was correlated with EPP rates in mammals, while strength of pair bond failed to reach statistical significance. Our analyses showthat, once social monogamy has evolved, paternal care, and potentially also close bonds, may facilitate the evolution of genetic monogamy.German Science Foundation (HU 1746/2-1); Wenner-Gren Foundation; L.S.B. Leakey Foundation;National Geographic Society; National Science Foundation (BCS-0621020, 1219368, and 1232349); the University of Pennsylvania Research Foundation; the Zoological Society of San Dieg

Genetic Algorithm with Optimal Recombination for the Asymmetric Travelling Salesman Problem

We propose a new genetic algorithm with optimal recombination for the asymmetric instances of travelling salesman problem. The algorithm incorporates several new features that contribute to its effectiveness: (i) Optimal recombination problem is solved within crossover operator. (ii) A new mutation operator performs a random jump within 3-opt or 4-opt neighborhood. (iii) Greedy constructive heuristic of W.Zhang and 3-opt local search heuristic are used to generate the initial population. A computational experiment on TSPLIB instances shows that the proposed algorithm yields competitive results to other well-known memetic algorithms for asymmetric travelling salesman problem.Comment: Proc. of The 11th International Conference on Large-Scale Scientific Computations (LSSC-17), June 5 - 9, 2017, Sozopol, Bulgari

Management of pediatric radiation dose using Philips fluoroscopy systems DoseWise: perfect image, perfect sense

Although image quality (IQ) is the ultimate goal for accurate diagnosis and treatment, minimizing radiation dose is equally important. This is especially true when pediatric patients are examined, because their sensitivity to radiation-induced cancer is two to three times greater than that of adults. DoseWise is an ALARA-based philosophy within Philips Medical Systems that is active at every level of product design. It encompasses a set of techniques, programs and practices that ensures optimal IQ while protecting people in the X-ray environments. DoseWise methods include management of the X-ray beam, less radiation-on time and more dose information for the operator. Smart beam management provides automatic customization of the X-ray beam spectrum, shape, and pulse frequency. The Philips-patented grid-controlled fluoroscopy (GCF) provides grid switching of the X-ray beam in the X-ray tube instead of the traditional generator switching method. In the examination of pediatric patients, DoseWise technology has been scientifically documented to reduce radiation dose to <10% of the dose of traditional continuous fluoroscopy systems. The result is improved IQ at a significantly lower effective dose, which contributes to the safety of patients and staff

Three Dimensional Electrical Impedance Tomography

The electrical resistivity of mammalian tissues varies widely and is correlated with physiological function. Electrical impedance tomography (EIT) can be used to probe such variations in vivo, and offers a non-invasive means of imaging the internal conductivity distribution of the human body. But the computational complexity of EIT has severe practical limitations, and previous work has been restricted to considering image reconstruction as an essentially two-dimensional problem. This simplification can limit significantly the imaging capabilities of EIT, as the electric currents used to determine the conductivity variations will not in general be confined to a two-dimensional plane. A few studies have attempted three-dimensional EIT image reconstruction, but have not yet succeeded in generating images of a quality suitable for clinical applications. Here we report the development of a three-dimensional EIT system with greatly improved imaging capabilities, which combines our 64-electrode data-collection apparatus with customized matrix inversion techniques. Our results demonstrate the practical potential of EIT for clinical applications, such as lung or brain imaging and diagnostic screening

Successful new product development by optimizing development process effectiveness in highly regulated sectors: the case of the Spanish medical devices sector

Rapid development and commercialization of new products is of vital importance for small and medium sized enterprises (SME) in regulated sectors. Due to strict regulations, competitive advantage can hardly be achieved through the effectiveness of product concepts only. If an SME in a highly regulated sector wants to excell in new product development (NPD) performance, the company should focus on the flexibility, speed, and productivity of its NPD function: i.e. the development process effectiveness. Our main research goals are first to explore if SMEs should focus on their their development process effectiveness rather than on their product concept effectiveness to achieve high NPD performance; and second, to explore whether a shared pattern in the organization of the NPD function can be recognized to affect NPD performance positively. The medical devices sector in Spain is used as an example of a\ud highly regulated sector. A structured survey among 11 SMEs, of which 2 were studied also as in in-depth case studies, led to the following results. First of all, indeed the companies in the dataset which focused on the effectiveness of their development process, stood out in NPD performance. Further, the higher performing companies did have a number of commonalities in the organisation of their NPD function: 1) The majority of the higher performing firms had an NPD strategy characterized by a predominantly incremental project portfolio.\ud 2) a) Successful firms with an incremental project portfolio combined this with a functional team structure b) Successful firms with a radical project portfolio combined this with a heavyweight or autonomous team structure.\ud 3) A negative reciprocal relationship exists between formalization of the NPD processes and the climate of the NPD function, in that a formalized NPD process and an innovative climate do not seem to reinforce each other. Innovative climate combined with an informal NPD process does however contribute positively to NPD performance. This effect was stronger in combination with a radical project portfolio. The highest NPD performance was measured for companies focusing mainly on incremental innovation. It is argued that in highly regulated sectors, companies with an incremental product portfolio would benefit from employing a functional structure. Those companies who choose for a more radical project portfolio in highly regulated sectors should be aware\ud that they are likely to excell only in the longer term by focusing on strategic flexibility. In their NPD organization, they might be well advised to combine informal innovation processes with an innovative climate

Associations between health-related quality of life, physical function and fear of falling in older fallers receiving home care

Falls and injuries in older adults have significant consequences and costs, both personal and to society. Although having a high incidence of falls, high prevalence of fear of falling and a lower quality of life, older adults receiving home care are underrepresented in research on older fallers. The objective of this study is to determine the associations between health-related quality of life (HRQOL), fear of falling and physical function in older fallers receiving home care

A novel hybrid password authentication scheme based on text and image

Considering the popularity and wide deployment of text passwords, we predict that they will be used as a prevalent authentication mechanism for many years to come. Thus, we have carried out studies on mechanisms to enhance text passwords. These studies suggest that password space and memorability should be improved, with an additional mechanism based on images. The combination of text and images increases resistance to some password attacks, such as brute force and observing attacks. We propose a hybrid authentication scheme integrating text and recognition-based graphical passwords. This authentication scheme can reduce the phishing attacks because if users are deceived to share their key passwords, there is still a chance to save the complete password as attackers do not know the users' image preferences. In addition to the security aspect, the proposed authentication scheme increases memorability as it does not require users to remember long and complex passwords. Thus, with the proposed scheme users will be able to create strong passwords without sacrificing usability. The hybrid scheme also offers an enjoyable sign-in/log-in experience to users

Reverberant cavity photoacoustic imaging

The number of ultrasound detectors required to produce photoacoustic tomography images can be reduced significantly by fully enclosing the imaging target in an acoustically reverberant cavity and exploiting the multiple reflections. This is demonstrated experimentally

Mutation Symmetries in BPS Quiver Theories: Building the BPS Spectra

We study the basic features of BPS quiver mutations in 4D $\mathcal{N}=2$ supersymmetric quantum field theory with $G=ADE$ gauge symmetries.\ We show, for these gauge symmetries, that there is an isotropy group $\mathcal{G}_{Mut}^{G}$ associated to a set of quiver mutations capturing information about the BPS spectra. In the strong coupling limit, it is shown that BPS chambers correspond to finite and closed groupoid orbits with an isotropy symmetry group $\mathcal{G}_{strong}^{G}$ isomorphic to the discrete dihedral groups $Dih_{2h_{G}}$ contained in Coxeter$(G)$ with $$ the Coxeter number of G. These isotropy symmetries allow to determine the BPS spectrum of the strong coupling chamber; and give another way to count the total number of BPS and anti-BPS states of $\mathcal{N}=2$ gauge theories. We also build the matrix realization of these mutation groups $\mathcal{G}_{strong}^{G}$ from which we read directly the electric-magnetic charges of the BPS and anti-BPS states of $\mathcal{N}=2$ QFT$_{4}$ as well as their matrix intersections. We study as well the quiver mutation symmetries in the weak coupling limit and give their links with infinite Coxeter groups. We show amongst others that $\mathcal{G}_{weak}^{su_{2}}$ is contained in ${GL}({2,}\mathbb{Z})$; and isomorphic to the infinite Coxeter ${I_{2}^{\infty}}$. Other issues such as building $\mathcal{G}$ and $\mathcal{G}_{weak}^{su_{3}}$ are also studied.Comment: LaTeX, 98 pages, 18 figures, Appendix I on groupoids adde