Constitutional mismatch repair deficiency syndrome with atypical features caused by a homozygous MLH1 missense variant (c.1918C>A, p.(Pro640Thr)): a case report

Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare autosomal recessive genetic disorder caused by biallelic germline mutations in one of the mismatch repair genes. Carriers are at exceptionally high risk for developing, typically in early life, hematological and brain malignancies, as well as cancers observed in Lynch syndrome. We report a homozygous MLH1 missense variant (c.1918C>A p.(Pro640Thr)) in a Tunisian patient with CMMRD syndrome and a family history of early-age colorectal cancer. The proband presented initially with colonic oligopolyposis and adenosquamous carcinoma of the caecum. He later developed several malignancies, including undifferentiated carcinoma of the parotid, grade 4 IDH-mutant astrocytoma, and ampulla of Vater adenocarcinoma. The patient was older than typical for this disease and had a remarkably prolonged survival despite developing four distinct aggressive malignancies. The current report highlights the challenges in assessing the pathogenicity of the identified variant and the remarkable phenotypic diversity in CMMRD

A severe clinical phenotype of Noonan syndrome with neonatal hypertrophic cardiomyopathy in the second case worldwide with RAF1 S259Y neomutation

International audienceNoonan syndrome and related disorders are a group of clinically and genetically heterogeneous conditions caused by mutations in genes of the RAS/MAPK pathway. Noonan syndrome causes multiple congenital anomalies, which are frequently accompanied by hypertrophic cardiomyopathy (HCM). We report here a Tunisian patient with a severe phenotype of Noonan syndrome including neonatal HCM, facial dysmorphism, severe failure to thrive, cutaneous abnormalities, pectus excavatum and severe stunted growth, who died in her eighth month of life. Using whole exome sequencing, we identified a de novo mutation in exon 7 of the RAF1 gene: c.776C > A (p.Ser259Tyr). This mutation affects a highly conserved serine residue, a main mediator of Raf-1 inhibition via phosphorylation. To our knowledge the c.776C > A mutation has been previously reported in only one case with prenatally diagnosed Noonan syndrome. Our study further supports the striking correlation of RAF1 mutations with HCM and highlights the clinical severity of Noonan syndrome associated with a RAF1 p.Ser259Tyr mutation

A functional approach to nonstationary signal analysis with automotive applications.

Motivated by the strong need for the improvement of road vehicle suspensions, this thesis is concerned with theoretical and applied problems pertaining to the proper development and operation of fully active suspension systems. Towards this end, a typical quarter-car hydraulic active suspension configuration is studied, and a non-linear computer-simulation mathematical model of it developed. This model captures the dynamics of the actuator and its associated hydraulic components in detail. These components include suspension bushing, pump accumulator, and power and bypass valves. The models of these components capture such physical characteristics as non-linear pressure-flow relationships, fluid compressibility, pump and valve non-linearities, leakages, and seal friction. Simulation results are in substantial qualitative agreement with experimental measurements. The developed model is suitable for analysis, design, control law optimization, and diagnostic strategies development. As part of the vehicle control strategy, the problem of on-board active suspension power demand prediction is considered. Using both simulated and experimental data, the power demand signal is found to be a nonstationary stochastic process, with stationarity approximately achieved in case an averaged version of it is considered. This approximately stationary case is studied first, and two different types of prediction schemes, referred to as direct and indirect, are developed based on novel and fast (microcomputer-suitable) signal estimation/prediction techniques that use the power demand signal history alone. The good performance characteristics of both types of schemes are verified. In addressing the nonstationary case, a broad and basic study on the estimation and prediction of nonstationary stochastic signals is undertaken. Time-varying AutoRegressive Moving Average (TARMA) signal representations, with coefficients being explicit functions of time, are considered. Certain fundamental properties of these models are examined, and a novel and fast estimation and prediction method is developed. By offering a computational complexity that is at least two to three orders of magnitude smaller than that of the alternative Prediction Error approach, overcoming non-linear search procedures and difficulties associated with local extrema, and requiring no initial guess parameter values, this method is the first TARMA approach suitable for engineering applications and unintended operation. The effectiveness of the nonstationary prediction method is finally demonstrated by using experimental vehicle data.Ph.D.Applied SciencesAutomotive engineeringMechanical engineeringSystems scienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/129245/2/9423142.pd

Review of Zinc Oxide Piezoelectric Nanogenerators: Piezoelectric Properties, Composite Structures and Power Output

Lead-containing piezoelectric materials typically show the highest energy conversion efficiencies, but due to their toxicity they will be limited in future applications. In their bulk form, the piezoelectric properties of lead-free piezoelectric materials are significantly lower than lead-containing materials. However, the piezoelectric properties of lead-free piezoelectric materials at the nano scale can be significantly larger than the bulk scale. This review looks at the suitability of ZnO nanostructures as candidate lead-free piezoelectric materials for use in piezoelectric nanogenerators (PENGs) based on their piezoelectric properties. Of the papers reviewed, Neodymium-doped ZnO nanorods (NRs) have a comparable piezoelectric strain constant to bulk lead-based piezoelectric materials and hence are good candidates for PENGs. Piezoelectric energy harvesters typically have low power outputs and an improvement in their power density is needed. This review systematically reviews the different composite structures of ZnO PENGs to determine the effect of composite structure on power output. State-of-the-art techniques to increase the power output of PENGs are presented. Of the PENGs reviewed, the highest power output belonged to a vertically aligned ZnO nanowire (NWs) PENG (1-3 nanowire composite) with a power output of 45.87 μW/cm2 under finger tapping. Future directions of research and challenges are discussed

Analysis of Optical Diffraction Profiles Created by Phase-Modulating MEMS Micromirror Arrays

This paper presents modeling and analysis of light diffraction and light-intensity modulation performed by an optical phased array (OPA) system based on metal-coated silicon micromirrors. The models can be used in the design process of a microelectromechanical system (MEMS)-based OPA device to predict its optical performance in terms of its field of view, response, angular resolution, and long-range transmission. Numerical results are derived using an extended model for the 1st-order diffracted light intensity modulation due to phase shift. The estimations of the optical characteristics are utilized in the designs of an OPA system capable of active phase modulation and an OPA system capable of array pitch tuning. Both designs are realized using the Multi-User MEMS Processes (PolyMUMPs) in which polysilicon is used as structural material for the MEMS-actuated mirrors. The experiments are performed to evaluate the optical performance of the prototypes. The tests show that the individually actuated micromirrors, which act as phase shifters, can transmit the most optical power along the 1st-order diffracted beam by actively changing their out-of-plane positions. In addition, the 1st-order diffracted beam with high optical intensity can be steered for distance measurement

Using capacitance measurements in EWOD devices to identify fluid composition and control droplet mixing

The use of capacitance measurements to identify the composition of droplets and monitor mixing in electrowetting on dielectric devices is examined here. Measurements were repeatable at each addressable location, with standard deviations on the order of 0.1 pF and a two-point calibration allowed repeatable differentiation of water–methanol solutions as the capacitance was linear with concentration. Capacitance at addressable locations was monitored throughout the mixing of water–methanol solutions. It was shown analytically and experimentally that the dimensionless capacitance is approximately equal to the dimensionless dielectric constant for practical EWOD applications. The number of cycles required for complete mixing remained constant for periods of actuation between 400 and 1000ms and applied voltages between 90 and 110VRMS. Although minimizing actuation period and maximizing droplet velocity decreases mixing time, these parameters have little affect on the number of cycles necessary to achieve mixing in EWOD devices. This shows mixing efficiency in EWOD devices is better described by the number of cycles, not the time, required for full mixing.NSER

Recursive identification of vibrating structures from noise-corrupted observations

http://deepblue.lib.umich.edu/bitstream/2027.42/3519/5/bad0663.0001.001.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/3519/4/bad0663.0001.001.tx