A disease approach using linkage analysis: Still in geneticists’ quiver

Linkage analysis, based on Mendel’s law of independent assortment, has contributed the most to the late advance of human genetics. In this article we present a way of approaching a disease by the use of this technique. The first step is to use a set of families where the disease segregates. Large pedigrees are preferable. Then all the members of these families are analyzed using an initial set of markers to detect an area of high interest. A common approach is to re-examine the same families with markers spaced closer to the chromosome in order to narrow the relevant area. Later, taking into account the existing knowledge, the hypothesis of the candidate gene is made and we try to prove it. The final study, as well as the final result are both influenced by the kind of families that are chosen, the suitability of the markers and the criteria used for proving a candidate gene hypothesis. Mendelian diseases were the first to be studied, but the real challenge for geneticists is detecting loci influencing complex diseases and linkage analysis remains still an effective approach

Final results from the EU project AVATAR: aerodynamic modelling of 10 MW wind turbines

This paper presents final results from the EU project AVATAR in which aerodynamic models are improved and validated for wind turbines on a scale of 10 MW and more. Special attention is paid to the improvement of low fidelity engineering (BEM based) models with higher fidelity (CFD) models but also with intermediate fidelity free vortex wake (FVW) models. The latter methods were found to be a good basis for improvement of induction modelling in engineering methods amongst others for the prediction of yawed cases, which in AVATAR was found to be one of the most challenging subjects to model. FVW methods also helped to improve the prediction of tip losses. Aero-elastic calculations with BEM based and FVW based models showed that fatigue loads for normal production cases were over predicted with approximately 15% or even more. It should then be realised that the outcome of BEM based models does not only depend on the choice of engineering add-ons (as is often assumed) but it is also heavily dependent on the way the induced velocities are solved. To this end an annulus and element approach are discussed which are assessed with the aid of FVW methods. For the prediction of fatigue loads the so-called element approach is recommended but the derived yaw models rely on an annulus approach which pleads for a generalised solution method for the induced velocities

Crystal Lattice Desolvation Effects On The Magnetic Quantum Tunneling Of Single-Molecule Magnets

High-frequency electron paramagnetic resonance (HFEPR) and alternating current (ac) susceptibility measurements are reported for a new high-symmetry Mn12 complex, [Mn12O12(O2CCH3)16(CH3OH)4]⋅CH3OH. The results are compared to those of other high-symmetry spin S=10 Mn12 single-molecule magnets (SMMs), including the original acetate, [Mn12(O2CCH3)16(H2O)4]⋅2CH3CO2H⋅4H2O, and the [Mn12O12(O2CCH2Br)16(H2O)4]⋅4CH2Cl2 and [Mn12O12(O2CCH2But)16(CH3OH)4]⋅CH3OH complexes. These comparisons reveal important insights into the factors that influence the values of the effective barrier to magnetization reversal, Ueff, deduced on the basis of ac susceptibility measurements. In particular, we find that variations in Ueff can be correlated with the degree of disorder in a crystal which can be controlled by desolvating (drying) samples. This highlights the importance of careful sample handling when making measurements on SMM crystals containing volatile lattice solvents. The HFEPR data additionally provide spectroscopic evidence suggesting that the relatively weak disorder induced by desolvation influences the quantum tunneling interactions and that it is under-barrier tunneling that is responsible for a consistent reduction in Ueff that is found upon drying samples. Meanwhile, the axial anisotropy deduced from HFEPR is found to be virtually identical for all four Mn12 complexes, with no measurable reduction upon desolvation

Choledochoduodenal fistula presenting with pneumobilia in a patient with gallbladder cancer: a case report

<p>Abstract</p> <p>Introduction</p> <p>Spontaneous biliary tract fistulas are rare entities. Most of them are associated with long-standing gallstones (especially common bile duct stones, or recurrent biliary tract infections), some with more uncommon diseases such as gallbladder cancer. Some authors believe that back flow from fistulas predisposes patients to gallbladder cancer and some believe that cancer causes necrosis and fistula formation. Gallbladder cancer has a dismal prognosis and 85% of patients are dead within a year of diagnosis. A common complication of gallbladder cancer is obstruction of the common bile duct, which may produce multiple intra-hepatic abscesses in or near the tumor-laden gallbladder. Fistula formation may further complicate the clinical picture.</p> <p>Case presentation</p> <p>We present a case of choledochoduodenal fistula in a 60-year-old diabetic African-American woman with gallbladder cancer. The initial clinical presentation was confusing and complex. Our patient was also found to have a gallbladder fossa abscess that was drained percutaneously as another complicating factor relating to her cancer. She developed myocardial infarction, massive upper gastrointestinal bleeding and respiratory arrest during her stay in hospital. Computed tomography was very helpful in assessing our patient and we discuss how, in a patient with pneumobilia, it can be helpful for detecting fistula, air in bile ducts or to show contractions of the gallbladder.</p> <p>Conclusions</p> <p>We believe this case merits reporting as it shows an entity that is not frequently thought of, is hard to diagnose and can be fatal, as in our patient. Careful evaluation, and computed tomography studies and endoscopic retrograde cholangio-pancreatography are helpful in early diagnosis and finding better management options for these patients.</p

Magnetic Quantum Tunneling: Insights from Simple Molecule-Based Magnets

This article takes a broad view of the understanding of magnetic bistability and magnetic quantum tunneling in single-molecule magnets (SMMs), focusing on three families of relatively simple, low-nuclearity transition metal clusters: spin S = 4 Ni4, Mn(III)3 (S = 2 and 6) and Mn(III)6 (S = 4 and 12). The Mn(III) complexes are related by the fact that they contain triangular Mn3 units in which the exchange may be switched from antiferromagnetic to ferromagnetic without significantly altering the coordination around the Mn(III) centers, thereby leaving the single-ion physics more-or-less unaltered. This allows for a detailed and systematic study of the way in which the individual-ion anisotropies project onto the molecular spin ground state in otherwise identical low- and high-spin molecules, thus providing unique insights into the key factors that control the quantum dynamics of SMMs, namely: (i) the height of the kinetic barrier to magnetization relaxation; and (ii) the transverse interactions that cause tunneling through this barrier. Numerical calculations are supported by an unprecedented experimental data set (17 different compounds), including very detailed spectroscopic information obtained from high-frequency electron paramagnetic resonance and low-temperature hysteresis measurements. Diagonalization of the multi-spin Hamiltonian matrix is necessary in order to fully capture the interplay between exchange and local anisotropy, and the resultant spin-state mixing which ultimately gives rise to the tunneling matrix elements in the high symmetry SMMs (ferromagnetic Mn3 and Ni4). The simplicity (low-nuclearity, high-symmetry, weak disorder, etc..) of the molecules highlighted in this study proves to be of crucial importance.Comment: 32 pages, incl. 6 figure

A voxelized immersed boundary (VIB) finite element method for accurate and efficient blood flow simulation

We present an efficient and accurate immersed boundary (IB) finite element (FE) method for internal flow problems with complex geometries (e.g., blood flow in the vascular system). In this study, we use a voxelized flow domain (discretized with hexahedral and tetrahedral elements) instead of a box domain, which is frequently used in IB methods. The proposed method utilizes the well-established incremental pressure correction scheme (IPCS) FE solver, and the boundary condition-enforced IB (BCE-IB) method to numerically solve the transient, incompressible Navier--Stokes flow equations. We verify the accuracy of our numerical method using the analytical solution for the Poiseuille flow in a cylinder, and the available experimental data (laser Doppler velocimetry) for the flow in a three-dimensional 90{\deg} angle tube bend. We further examine the accuracy and applicability of the proposed method by considering flow within complex geometries, such as blood flow in aneurysmal vessels and the aorta, flow configurations that would otherwise be difficult to solve by most IB methods. Our method offers high accuracy, as demonstrated by the verification examples, and high applicability, as demonstrated through the solution of blood flow within complex geometry. The proposed method is efficient, since it is as fast as the traditional finite element method used to solve the Navier--Stokes flow equations, with a small overhead (not more than 5$\%$) due to the numerical solution of a linear system formulated for the IB method.Comment: arXiv admin note: substantial text overlap with arXiv:2007.0208