A stable FSI algorithm for light rigid bodies in compressible flow

In this article we describe a stable partitioned algorithm that overcomes the added mass instability arising in fluid-structure interactions of light rigid bodies and inviscid compressible flow. The new algorithm is stable even for bodies with zero mass and zero moments of inertia. The approach is based on a local characteristic projection of the force on the rigid body and is a natural extension of the recently developed algorithm for coupling compressible flow and deformable bodies. Normal mode analysis is used to prove the stability of the approximation for a one-dimensional model problem and numerical computations confirm these results. In multiple space dimensions the approach naturally reveals the form of the added mass tensors in the equations governing the motion of the rigid body. These tensors, which depend on certain surface integrals of the fluid impedance, couple the translational and angular velocities of the body. Numerical results in two space dimensions, based on the use of moving overlapping grids and adaptive mesh refinement, demonstrate the behavior and efficacy of the new scheme. These results include the simulation of the difficult problem of a shock impacting an ellipse of zero mass.Comment: 32 pages, 20 figure

The effect of racemic gossypol and AT-101 on angiogenic profile of OVCAR-3 cells: a preliminary molecular framework for gossypol enantiomers

To compare the effect of racemic gossypol with its (–)/(–) enantiomer (AT-101) on expression profiles of angiogenic molecules by mRNA levels in human ovarian cancer cell line OVCAR-3. Methods: Cell viability assay (2,3-bis (2-methoxy-4-nitro-5- sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide) was used to detect cytotoxicity of gossypol enantiomers. DNA fragmentation by an enzyme-linked immunosorbent (ELISA) assay was used to evaluate the rate of apoptosis. The mRNA expression levels of angiogenic molecules were investigated by Human Angiogenesis RT2 ProfilerTM PCR Array (SuperArray, Frederick, MD). Results: Both racemic form and AT-101 resulted in a significant cytotoxicity and induced apoptosis. This effect was observed in a dose- and time dependent manner. However, AT-101 was much more potent. In addition, the treatment of 10 μM of racemic gossypol alone and 3 μM of AT-101 alone resulted in significant down-regulation (≥ 3 fold) in mRNA levels of some pivotal angiogenic molecules in OVCAR-3, but altered gene profiles were different by the treatment of each enantiomer. Conclusion: The efficacy of two gossypol enantiomers in OVCAR-3 cells showed distinction. AT-101 was much more potent than racemic gossypol, not only by means of cell death and apoptosis, but also by modulation of angiogenic molecules released from OVCAR-3 cells. Further studies with endothelial cells should be done to verify the anti-angiogenic effect of gossypol enantiomers in cancer treatment

Solitary lower lumbar osteochondroma (spinous process of L3 involvement): a case report

Solitary osteochondromas, which are the most common benign bone tumors of long bones, are rarely found in the vertebral column. A 16-year-old female patient presented with a hard palpable mass at lower lumbar region like a congenital deformity. Plain radiography illustrated a well-defined solid mass arising from the posterior elements of the L3 and ruled out any congenital anomalies. A computed tomography scan further determined a mass that arose from the spinous process of L3. The tumor was excised en bloc through a posterior approach and histopathological examination verified the diagnosis of osteocondroma

Cerebellopontine epidermoid presenting with trigeminal neuralgia for 10 years: a case report

Trigeminal neuralgia, also called tic douloureux, is a common and potentially disabling pain syndrome, which affects the trigeminal or fifth cranial nerve. The precise pathophysiology of Trigeminal neuralgia remains obscure. The disorder causes extreme, sporadic, sudden burning or shock-like face pain that lasts from few seconds to minutes and can be physically and mentally incapacitating. More than one nerve branch can be affected by the disorder. A 55-year-old female presented with pain over the left side of face for 10 years uncontrolled with carbamazepine. On examination the positive findings were reduced sensation by 25% over the left side of face with House and Brackman grade II facial nerve palsy. The corneal reflex was absent on left side. Magnetic resonance imaging showed left cerebellopontine angle (CPA) mass suggestive of an epidermoid involving the Vth nerve and Gasserian ganglion and extending into the middle cranial fossa. She underwent left suboccipital craniectomy and near total excision of the tumor with decompression of the Vth nerve which was fully engulfed by the tumor. Postoperative the VII nerve palsy increased to grade III and she had 50% loss of sensation over left side. She had no further attacks of pain and hence tapered off the carbamazepine. TN caused by cerebellopontine angle epidermoids is uncommon and should be kept in view in all cases presenting with TN. The aim of surgery for epidermoids is to decompress the cranial nerves and brain stem and not total removal with its attendant morbidity and mortality

Prenatal muscle development in a mouse model for the secondary dystroglycanopathies

The defective glycosylation of α-dystroglycan is associated with a group of muscular dystrophies that are collectively referred to as the secondary dystroglycanopathies. Mutations in the gene encoding fukutin-related protein (FKRP) are one of the most common causes of secondary dystroglycanopathy in the UK and are associated with a wide spectrum of disease. Whilst central nervous system involvement has a prenatal onset, no studies have addressed prenatal muscle development in any of the mouse models for this group of diseases. In view of the pivotal role of α-dystroglycan in early basement membrane formation, we sought to determine if the muscle formation was altered in a mouse model of FKRP-related dystrophy

Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy

OBJECTIVE To expand the clinical phenotype of autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) due to mutations in the dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene. METHODS Patients with a phenotype suggestive of a motor, non-length-dependent neuronopathy predominantly affecting the lower limbs were identified at participating neuromuscular centers and referred for targeted sequencing of DYNC1H1. RESULTS We report a cohort of 30 cases of SMA-LED from 16 families, carrying mutations in the tail and motor domains of DYNC1H1, including 10 novel mutations. These patients are characterized by congenital or childhood-onset lower limb wasting and weakness frequently associated with cognitive impairment. The clinical severity is variable, ranging from generalized arthrogryposis and inability to ambulate to exclusive and mild lower limb weakness. In many individuals with cognitive impairment (9/30 had cognitive impairment) who underwent brain MRI, there was an underlying structural malformation resulting in polymicrogyric appearance. The lower limb muscle MRI shows a distinctive pattern suggestive of denervation characterized by sparing and relative hypertrophy of the adductor longus and semitendinosus muscles at the thigh level, and diffuse involvement with relative sparing of the anterior-medial muscles at the calf level. Proximal muscle histopathology did not always show classic neurogenic features. CONCLUSION Our report expands the clinical spectrum of DYNC1H1-related SMA-LED to include generalized arthrogryposis. In addition, we report that the neurogenic peripheral pathology and the CNS neuronal migration defects are often associated, reinforcing the importance of DYNC1H1 in both central and peripheral neuronal functions

Anticancer Gene Transfer for Cancer Gene Therapy

Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field

HDG-NEFEM with Degree Adaptivity for Stokes Flows

This paper presents the first degree adaptive procedure able to directly use the geometry given by a CAD model. The technique uses a hybridisable discontinuous Galerkin discretisation combined with a NURBS-enhanced rationale, completely removing the uncertainty induced by a polynomial approximation of curved boundaries that is common within an isoparametric approach. The technique is compared against two strategies to perform degree adaptivity currently in use. This paper demonstrates, for the first time, that the most extended technique for degree adaptivity can easily lead to a non-reliable error estimator if no communication with CAD software is introduced whereas if the communication with the CAD is done, it results in a substantial computing time. The proposed technique encapsulates the CAD model in the simulation and is able to produce reliable error estimators irrespectively of the initial mesh used to start the adaptive process. Several numerical examples confirm the findings and demonstrate the superiority of the proposed technique. The paper also proposes a novel idea to test the implementation of high-order solvers where different degrees of approximation are used in different elements

A homozygous AKNA frameshift variant is associated with microcephaly in a Pakistani family

Primary microcephaly (MCPH) is a prenatal condition of small brain size with a varying degree of intellectual disability. It is a heterogeneous genetic disorder with 28 associated genes reported so far. Most of these genes encode centrosomal proteins. Recently, AKNA was recognized as a novel centrosomal protein that regulates neurogenesis via microtubule organization, making AKNA a likely candidate gene for MCPH. Using linkage analysis and whole-exome sequencing, we found a frameshift variant in exon 12 of AKNA (NM_030767.4: c.2737delG) that cosegregates with microcephaly, mild intellectual disability and speech impairment in a consanguineous family from Pakistan. This variant is predicted to result in a protein with a truncated C-terminus (p.(Glu913Argfs*42)), which has been shown to be indispensable to AKNA’s localization to the centrosome and a normal brain development. Moreover, the amino acid sequence is altered from the beginning of the second of the two PEST domains, which are rich in proline (P), glutamic acid (E), serine (S), and threonine (T) and common to rapidly degraded proteins. An impaired function of the PEST domains may affect the intracellular half-life of the protein. Our genetic findings compellingly substantiate the predicted candidacy, based on its newly ascribed functional features, of the multifaceted protein AKNA for association with MCPH