Optimal design of phononic media through genetic algorithm-informed pre-stress for the control of antiplane wave propagation

In this paper we employ genetic algorithms in order to theoretically design a range of phononic media that can act to prevent or ensure antiplane elastic wave propagation over a specific range of low frequencies, with each case corresponding to a specific pre-stress level. The medium described consists of an array of cylindrical annuli embedded inside an elastic matrix. The annuli are considered as capable of large strain and their constitutive response is described by the popular Mooney–Rivlin strain energy function. The simple nature of the medium described is an alternative approach to topology optimization in phononic media, which although useful, often gives rise to complex phase distributions inside a composite material, leading to more complicated manufacturing requirements

Argentum-quarz solution in the treatment of anorectal fistulas: Is it possible a conservative approach?

Patients suffering from chronic intestinal diseases (Crohn's disease, Ulcerative Colitis, Indeterminate Colitis) are prone to the development of pyogenic complications. These complications are most commonly in the form of perianal or intraabdominal abscesses and/or fistulas. The treatment of these complications are managed differently but, after an initial treatment based on medical or minimally invasive management, the solution of the pathological condition is always achieved by a surgical procedure. In the last few years prospective studies have proposed an alternative conservative therapeutic approach based on application of fibrin glue in the healing of patients with fistulas-in-ano. In this paper we suggest and discuss the therapeutic potential of silver and quarz in the conservative treatment of anorectal fistulas pointing out their role in modulating particular steps of the pathogenetic process which characterizes this pathological condition

Combinatorial effects on gene expression at the Lbx1/Fgf8 locus resolve Split-Hand/Foot Malformation type 3

Split-Hand/Foot Malformation type 3 (SHFM3) is a congenital limb malformation associated with tandem duplications at the LBX1/FGF8 locus. Yet, the disease patho-mechanism remains unsolved. Here we investigated the functional consequences of SHFM3-associated rearrangements on chromatin conformation and gene expression in vivo in transgenic mice. We show that the Lbx1/Fgf8 locus consists of two separate, but interacting, regulatory domains. Re-engineering of a SHFM3-associated duplication and a newly reported inversion in mice resulted in restructuring of the chromatin architecture. This led to an ectopic activation of the Lbx1 and Btrc genes in the apical ectodermal ridge (AER) in an Fgf8-like pattern. Artificial repositioning of the AER-specific enhancers of Fgf8 was sufficient to induce misexpression of Lbx1 and Btrc. We provide evidence that the SHFM3 phenotype is the result of a combinatorial effect on gene misexpression and dosage in the developing limb. Our results reveal new insights into the molecular mechanism underlying SHFM3 and provide novel conceptual framework for how genomic rearrangements can cause gene misexpression and disease

MANAGEMENT OF LEIOMYOMA OF THE TRANSVERSE COLON: CASE REPORT

Colonic leiomyoma is a mesenchymal tumor that arises from the muscularis mucosae or muscularis propria and is composed of well-differentiated smooth muscle cells with no atypia. It is often incidentally found since its growth affects the submucosal layer and the lesion is covered with normal epithelium. Endoscopic ultrasonography is recommended to define the grade of infiltration of the tumor and eventually lymph node involvement. Histological examination is critical to establish the nature of the tumor and its behaviour. In the case of a voluminous tumor surgical treatment is needed. we report case of a patient that underwent colonoscopy showing the presence of a neoformation at 70 cm from ileocecal valve occupying half lumen of transverse colon. A surgical resection was performed and histological analysis confirmed the presence of a leiomyoma

Functional evidence of mTORβ splice variant involvement in the pathogenesis of congenital heart defects

mTOR dysregulation has been described in pathological conditions, such as cardiovascular and overgrowth disorders. Here we report on the first case of a patient with a complex congenital heart disease and an interstitial duplication in the short arm of chromosome 1, encompassing part of the mTOR gene. Our results suggest that an intragenic mTOR microduplication might play a role in the pathogenesis of non-syndromic congenital heart defects (CHDs) due to an upregulation of mTOR/Rictor and consequently an increased phosphorylation of PI3K/AKT and MEK/ERK signaling pathways in patient-derived amniocytes. This is the first report which shows a causative role of intragenic mTOR microduplication in the etiology of an isolated complex CHD

The Novel Mouse Mutation Oblivion Inactivates the PMCA2 Pump and Causes Progressive Hearing Loss

Progressive hearing loss is common in the human population, but we have few clues to the molecular basis. Mouse mutants with progressive hearing loss offer valuable insights, and ENU (N-ethyl-N-nitrosourea) mutagenesis is a useful way of generating models. We have characterised a new ENU-induced mouse mutant, Oblivion (allele symbol Obl), showing semi-dominant inheritance of hearing impairment. Obl/+ mutants showed increasing hearing impairment from post-natal day (P)20 to P90, and loss of auditory function was followed by a corresponding base to apex progression of hair cell degeneration. Obl/Obl mutants were small, showed severe vestibular dysfunction by 2 weeks of age, and were completely deaf from birth; sensory hair cells were completely degenerate in the basal turn of the cochlea, although hair cells appeared normal in the apex. We mapped the mutation to Chromosome 6. Mutation analysis of Atp2b2 showed a missense mutation (2630C→T) in exon 15, causing a serine to phenylalanine substitution (S877F) in transmembrane domain 6 of the PMCA2 pump, the resident Ca2+ pump of hair cell stereocilia. Transmembrane domain mutations in these pumps generally are believed to be incompatible with normal targeting of the protein to the plasma membrane. However, analyses of hair cells in cultured utricular maculae of Obl/Obl mice and of the mutant Obl pump in model cells showed that the protein was correctly targeted to the plasma membrane. Biochemical and biophysical characterisation showed that the pump had lost a significant portion of its non-stimulated Ca2+ exporting ability. These findings can explain the progressive loss of auditory function, and indicate the limits in our ability to predict mechanism from sequence alone

Finding New Genes for Non-Syndromic Hearing Loss through an In Silico Prioritization Study

At present, 51 genes are already known to be responsible for Non-Syndromic hereditary Hearing Loss (NSHL), but the knowledge of 121 NSHL-linked chromosomal regions brings to the hypothesis that a number of disease genes have still to be uncovered. To help scientists to find new NSHL genes, we built a gene-scoring system, integrating Gene Ontology, NCBI Gene and Map Viewer databases, which prioritizes the candidate genes according to their probability to cause NSHL. We defined a set of candidates and measured their functional similarity with respect to the disease gene set, computing a score () that relies on the assumption that functionally related genes might contribute to the same (disease) phenotype. A Kolmogorov-Smirnov test, comparing the pair-wise distribution on the disease gene set with the distribution on the remaining human genes, provided a statistical assessment of this assumption. We found at a p-value that the former pair-wise is greater than the latter, justifying a prioritization strategy based on the functional similarity of candidate genes respect to the disease gene set. A cross-validation test measured to what extent the ranking for NSHL is different from a random ordering: adding 15% of the disease genes to the candidate gene set, the ranking of the disease genes in the first eight positions resulted statistically different from a hypergeometric distribution with a p-value and a power. The twenty top-scored genes were finally examined to evaluate their possible involvement in NSHL. We found that half of them are known to be expressed in human inner ear or cochlea and are mainly involved in remodeling and organization of actin formation and maintenance of the cilia and the endocochlear potential. These findings strongly indicate that our metric was able to suggest excellent NSHL candidates to be screened in patients and controls for causative mutations

Investigation of Short Injections Using Standard and Modified Common Rail Injectors

ABSTRACT−The control of the fuel to be introduced into the combustion chamber under idling and low-load conditions is known to be a problem in Diesel engines, owing to the relatively small fraction of the full-load fuel needed under light loads. Thus, particular attention should be paid to the behavior of the injector with reference to short injection events. This work presents the results of an experimental campaign carried out with two different types of common rail injectors, a standard injector and a modified one. The latter, coming from a simple modification realized in a standard injector, exhibits linear behavior between injected fuel and solenoid energizing time in the field of short injections. A direct comparison of the two injection behaviors suggests a possible way to better control short or pilot injections

Common Rail Injector Modified to Achieve a Modulation of the Injection Rate

ABSTRACT−Injection rate shape control is one feature of a diesel fuel injection system that is strongly desired at this time. In the conventional common rail system, it is difficult to control the injection rate since the fuel pressure is constant during the injection period, resulting in a nearly rectangular rate shape. In order to look into possible injection modulations, injectors equipped with standard and geometrically modified control valves were investigated in detail by means of computer modelling and simulation. Experiments were carried out to validate the feasibility of such a shaping. The results of this study show a noteworthy dependence of the fuel rate on geometrical modifications in the piloting stage of the injector