Short Defects Research Articles

The impact of RABL2B gene (rs144944885) on human male infertility in patients with oligoasthenoteratozoospermia and immotile short tail sperm defects.

Male infertility is a multifactorial disorder with impressively genetic basis; besides, sperm abnormalities are the cause of numerous cases of male infertility. In this study, we evaluated the genetic variants in exons 4 and 5 and their intron-exon boundaries in RABL2B gene in infertile men with oligoasthenoteratozoospermia (OAT) and immotile short tail sperm (ISTS) defects to define if there is any association between these variants and human male infertility. To this purpose, DNA was extracted from peripheral blood and after PCR reaction and sequencing, the results of sequenced segments were analyzed. In the present study, 30 infertile men with ISTS defect and 30 oligoasthenoteratozoospermic infertile men were recruited. All men were of Iranian origin and it took 3years to collect patient's samples with ISTS defect. As a result, the 50776482 delC intronic variant (rs144944885) was identified in five patients with oligoasthenoteratozoospermia defect and one patient with ISTS defect in heterozygote form. This variant was not identified in controls. The allelic frequency of the 50776482 delC variant was significantly statistically higher in oligoasthenoteratozoospermic infertile men (p < 0.05). Bioinformatics studies suggested that the 50776482 delC allele would modify the splicing of RABL2B pre-mRNA. In addition, we identified a new genetic variant in RABL2B gene. According to the present study, 50776482 delC allele in the RABL2B gene could be a risk factor in Iranian infertile men with oligoasthenoteratozoospermia defect, but more genetic studies are required to understand the accurate role of this variant in pathogenesis of human male infertility.

Through Silicon Via (TSV) Defect Modeling, Measurement, and Analysis

Through silicon via (TSV)-based 3-D integrated circuit has introduced the solution to limitlessly growing demand on high system bandwidth, low power consumption, and small form factor of electronic devices. As the system design aims for higher performance, the physical dimensions of the channels are continuously decreasing. With TSV diameter of less than 10 $\mu \text{m}$ and pitch of several tens of micrometers, the I/O count has increased up to the order of tens of thousands for wide bandwidth data transmission. However, without highly precise fabrication process, such small structures are susceptible to a variety of defects. For the first time, in this paper, we propose a noninvasive defect analysis method for high-speed TSV channel. With designed and fabricated test vehicles, the proposed method is demonstrated with ${S}$ -parameter and time-domain reflectometry measurement results. In addition, we present equivalent circuit models of TSV daisy-chain structures, including the circuit components for open defect and short defect. With characterized dominant factors in each frequency range, $S_{11}$ is analyzed to distinguish and locate the defects by the amount of capacitance, resistance, and inductance that the signal experiences. ${S}$ -parameter measurement sufficiently allows high-frequency defect analysis of TSV channel without destroying the test sample. We experimentally verified the accuracy of the suggested model by comparing the ${S}$ -parameter results from circuit simulations and measurements. Finally, the model is modified to discuss the effects of open defect and short defect on the electrical characteristics of TSV channel.

The effect of the local chemical composition of grain boundaries on the corrosion resistance of a titanium alloy

The influence of the structural-phase state of grain boundaries in a Ti4Al2V (commercial PT3V grade) pseudo-alpha-titanium alloy on its susceptibility to hot-salt intergranular corrosion (IGC) has been studied. It is established that IGC-tested alloy samples exhibit corrosion-induced defects of two types. More extended defects of the first type occur at the V-rich boundaries of coarse grains, while short defects of the second type reside at the grain boundaries with composition close to that of the grain body. The existence of the two types of IGC defects is explained by the classical theory of galvanic microcouples (microcells), according to which the IGC intensity is proportional to the difference of corrosion-active impurity concentrations between the grain boundary and body.

High-Frequency Testing of Vertical Interconnection Array Using Indirect Contact Probing Method With an Improved Calibration

As a solution to the need for efficient characterization of the vertical interconnection array, this paper presents an indirect contact probing method, adopting a dielectric contactor. The dielectric contactor protects vertical interconnections, resolves the issue of probe misalignments, and increases the coupling between probe tips and devices under test (DUTs). The characterization procedure is composed of the extraction of the dielectric contactor characteristic, the indirect contact measurement of DUTs, and de-embedding to obtain the DUT characteristics. To realize the multiport measurement, we propose an approximate method to formulate the scattering matrix of the dielectric contactor. For the design of calibration vias, the coaxial transmission line model with lumped elements is used, enhancing the available bandwidth of measurement. To verify the proposed method, a two-port network of two vias is characterized by numerical simulations up to 20 GHz. With the presented measurement setup, three cases of two vias are characterized up to 12 GHz. For the testing approach, DUTs containing open and short defects are fully tested by observing impedance curves up to 20 GHz.

Influence of intrinsic kink-like defects on screw dislocation – coherent twin boundary interactions in copper

The interaction mechanisms between a dislocation and a twin boundary in nanotwinned face-centered cubic metals are well understood in terms of perfect coherent interfaces. Processes involving intrinsic incoherent twin boundary defects, however, remain largely unexplored, despite recent evidence suggesting that imperfect twin boundaries containing short kink-like step defects contribute notably to plastic deformation and twin stability in large nanotwinned grains. Here, molecular dynamics simulation is used to study the underlying interaction of screw dislocations with either 0° or 60° atomic-scale kink twin boundary defects, in order to understand how the presence of imperfect twin boundaries can alter hardening and ductility mechanisms in nanotwinned copper. It is found that kinked twin boundaries are effective in changing the mechanisms from direct dislocation transmission to dislocation absorption when the applied shear strain exceeds 1.06%, with pronounced hardening arising from such transformation. Hardening by dislocation pinning from individual kink steps is also manifest for 60° intersections. On the contrary, twin boundary defects produce no hardening at low applied strains when dislocation absorption at the twin boundary is already prevailing.

Truncation and microdeletion of EVC/EVC2 with missense mutation of EFCAB7 in Ellis-van Creveld syndrome.

Ellis-van Creveld syndrome (EvC) is a ciliopathy with cardiac anomalies, disproportionate short stature, polydactyly, dystrophic nails and oral defects. To obtain further insight into the genetics of EvC, we screened EVC/EVC2 mutations in eight Vietnamese EvC patients. All the patients had a congenital heart defect with atypical oral and/or skeletal abnormalities. One had compound heterozygous EVC2 mutations: a novel mutation c.769G > T-p.E177X in exon 6 inherited from father and another previously reported c.2476C > T-p.R826X mutation in exon 14 inherited from mother. The EVC2 mRNA expression level was significantly lower in the patient and her parents compared to controls. Another case had a novel heterozygous EVC mutation (c.1717C > G-p.S572X) in exon 12, inherited from his father. Of note, the mother without any EVC mutation on Sanger sequencing showed a lower expression level of EVC mRNA compared with controls. SNP array analysis revealed that the patient and mother had a heterozygous 16.4 kb deletion in EVC. This patient also had a heterozygous novel variant in exon 9 of EFCAB7 (c.1171 T > C-p.Y391H), inherited from his father. The atypical cardiac phenotype of this patient and the father suggested that EFCAB7 may modify the phenotype by interacting with EVC. In conclusion, we detected two novel nonsense mutations and a partial deletion of EVC/EVC2 in two Vietnamese families with EvC. Moreover, we found in one family a missense mutation of EFCAB7, a possible modifier gene in EvC and its related disorders.

Robotic ultrasonic testing of AGR fuel cladding

The purpose of the presented work was to undertake experimental trials to demonstrate the potential capabilities of a novel in-situ robotic ultrasonic scanning technique for measuring and monitoring loss of the cladding wall thickness in fuel pins of Advanced Gas-cooled Reactors using non-radioactive samples. AGR fuel pins are stainless steel cylindrical ribbed pipes of inner diameter of the rod being about 15 mm and wall thickness of about 300 μm. Spent AGR fuel pins are stored in a water pond and thus may be prone to corrosion and stress-corrosion cracking under adverse conditions. An ultrasonic immersion transducer with central frequency of 25 MHz was used to measure wall thickness of the AGR fuel cladding. The novelty of the approach consists in the usage of a frequency domain technique to measure the wall thickness combined with cylindrical ultrasonic scanning of the samples performed using an industrial robotic manipulator. The frequency domain approach could detect wall thicknesses in the range 96 μm to 700 μm with a resolution of about 10 μm. In addition to the frequency domain measurements, using conventional time domain techniques, it was possible to detect very short (2.5 mm long) and shallow (100 μm in depth) crack-like defects in the fuel cladding.

Elliptical cross sectional shape of runner system in injection mold design

This paper presents a new cross sectional shape of the runner system in the mold design of the injection molding process. The aim of the new geometry is to reduce scrap, cycle time and ease the ejection of runner system from mold tools. An elliptical cross sectional shape of runner with different ratios was proposed for two circular flat plates with thickness 1 mm. Finite element method (FEM) is employed in SolidWorks Plastic for simulation of the injected part. Short shot defect in the plastic part during the injection molding process is analyzed by SolidWorks Plastic to validate the new proposed geometry. An experimental study of the injection molding process of polypropylene circular flat plates is conducted for the new geometry. The input machine parameters selected are filling time, melt temperature, mold temperature, pressure holding time, and pure cooling time. The research outcomes show no short shot defect associated with the new geometry and also significant 25 and 2.5 % reduction in scrap and cooling time respectively compared to round cross sections. Reduction in contact surface of the runner system with mold walls improved the ease of ejection of runner system out of the cavity as well. The contribution of this study is to design a new geometry of a cold runner system to reduce scrap, cycle time and also provide easy ejection of runner system in the injection molding.

Distal Inside-Out Epineural Sliding Technique to Repair Segmental Nerve Defects.

Background: The repair of a segmental peripheral nerve injury is a clinical challenge. Several studies have been performed to determine superior methods for overcoming nerve gaps. The purpose of this study was to investigate if the inside-out slided epineurium of the distal segment of an injured nerve can serve as a conduit to bridge a short nerve defect (10 mm). Methods: Nineteen sciatic nerves in Sprague-Dawley rats were transected, and a 10-mm gap was left between the ends. A section of distal epineurium was pulled inside out to bridge the gap. Walking track analysis was performed, and the sciatic function index (SFI) was calculated. Wet muscle mass and withdrawal reflex were measured. The density of axon fibers at different levels of repaired nerves was determined, and histological analysis was performed at 16 weeks. Results: The mean SFI improved from -81.0 at 4 weeks to 36.3 at 16 weeks. The axon densities showed regeneration through the epineural tube, and 5 of the rats demonstrated a withdrawal reflex. The weight of the tibialis anterior muscle of the injured limb at 16 weeks was 59% that of the uninjured side. Conclusions: The distal epineural sheath tube provided a size-matched conduit between the nerve stumps, with no histological donor-site morbidity. Histologically, regeneration occurred through the epineural tube without neuroma formation, and functional recovery was comparable to that of previous studies of nerve repair techniques. Technique may be an addition to the armamentarium of tools used to treat segmental nerve defects.

Effects of process parameters on the molding quality of the micro-needle array

Micro-needle array, which is used in medical applications, is a kind of typical injection molded products with microstructures. Due to its tiny micro-features size and high aspect ratios, it is more likely to produce short shots defects, leading to poor molding quality. The injection molding process of the micro-needle array was studied in this paper to find the effects of the process parameters on the molding quality of the micro-needle array and to provide theoretical guidance for practical production of high-quality products. With the shrinkage ratio and warpage of micro needles as the evaluation indices of the molding quality, the orthogonal experiment was conducted and the analysis of variance was carried out. According to the results, the contribution rates were calculated to determine the influence of various process parameters on molding quality. The single parameter method was used to analyse the main process parameter. It was found that the contribution rate of the holding pressure on shrinkage ratio and warpage reached 83.55% and 94.71% respectively, far higher than that of the other parameters. The study revealed that the holding pressure is the main factor which affects the molding quality of micro-needle array so that it should be focused on in order to obtain plastic parts with high quality in the practical production.

Diagnosis of Soft Spot Short Defects in Analog Circuits Considering the Thermal Behaviour of the Chip

Abstract The paper deals with fault diagnosis of nonlinear analogue integrated circuits. Soft spot short defects are analysed taking into account variations of the circuit parameters due to physical imperfections as well as self-heating of the chip. A method enabling to detect, locate and estimate the value of a spot defect has been developed. For this purpose an appropriate objective function was minimized using an optimization procedure based on the Fibonacci method. The proposed approach exploits DC measurements in the test phase, performed at a limited number of accessible points. For illustration three numerical examples are given.

Focused Rayleigh wave EMAT for characterisation of surface-breaking defects

Developments towards higher resolution and the ability to detect small defects are bringing a step-change in non-destructive testing. This paper presents a new method for increasing resolution, using a focused electromagnetic acoustic transducer (EMAT) optimised to generate Rayleigh waves at 2MHz. This high frequency allows detection of mm-depth defects, and the focusing allows sizing of much shorter defects than is possible when using standard EMATs. The focusing behaviour and the aperture angle effect are analysed using laser vibrometry and finite element modelling, showing that a reduced aperture shifts the focal point from the designed value and increases the focal depth. The dual-EMAT has excellent signal to noise ratio (up to 30dB) and has been used in single shot mode to image a variety of surface-breaking defects, including detecting and positioning a pair of real defects in an aluminium billet sample, and a machined defect of 2mm length, 0.2mm width, and 1.5mm depth, giving an upper limit on the defect length of 2.1±0.5mm. The results can be used to design an EMAT with optimised focal behaviour for defect detection.

Cavernous nerve reconstruction with autologous vein graft and platelet-derived growth factors.

In this study, we investigated the feasibility of using autologous vein graft and platelet-derived growth factors to bridge transected cavernous nerve in a rat model. A short defect in the bilateral cavernous nerve was created and repaired with vein graft from the right jugular vein or vein graft plus platelet-derived growth factors. The 32 rats were divided into four groups, namely Group 1 - no repair as a negative control, Group 2 - vein graft alone, Group 3 - vein graft plus platelet-derived growth factors, and Group 4 - sham operation as a positive control. We evaluated nerve regeneration and functional recovery using retrograde tracing study with FluoroGold, Toluidine blue staining of cavernous nerve, and the intracavernous pressure at 3 months. Three months after surgery, rich FluoroGold-positive cells were observed in the sham and vein graft plus platelet-derived growth factors group, but very few were found in the no repair group. The number of myelinated axons of regenerated cavernous nerve and intracavernous pressure were increased obviously in the two vein graft groups, especially in the vein graft plus platelet-derived growth factors group. These findings confirm the feasibility of using autologous vein as guides for cavernous nerve regeneration, and the regeneration can be further enhanced when the vein is filled with platelet-derived growth factors.

Effects of Binder and Processing Parameters on Processability of Porous Ti/HA Composite through Powder Injection Molding

Powder injection molding (PIM) process is suitable for both metal and ceramic materials to produce parts with high volume and accuracy at low cost. In this research work, 90wt. % of Ti6Al4V was dry mixed with 10wt. % of Hydroxyapatite (HA). The resultant mixture was further mixed with different space holders in weight ratio 8:2. The feedstock was prepared by mixing the final mixed powder with PEG and PW based binder systems. The dumbbell shape parts were produced using DSM Xplore injection molding machine. The molded samples were debound into two stages i.e solvent extraction followed by thermal debinding. The debinding parameters were optimized for different binder with space holders. The major binders’ paraffin wax (PW) extracted in haptane and PEG in water immersion at temperatures of 60 °C and 50 °C for 5 hrs respectively. The thermal de-binding was performed successfully at 500 °C by varying the heating rate from 3 °C/min-5 °C/min with holding time 1hr in argon atmosphere followed by the sintering in vacuum. During molding short shot defects and cracks were observed while during debinding, collection of binder, swelling and holes were noted. These types of defects may be due to space holder, improper binder, heating rate, temperature and dwell time at each processing step. The sintered test specimens were analyzed for porosity and microstructure. The results showed that the PEG based binder system with NaCl space holder is more effective to produce porous Ti/HA composite through PIM. Porous Ti/HA composite showed interconnected pores with average size of 90µm.

Ellis-van creveld syndrome with unusual Genitourinary findings: A case report

Ellis-van Creveld syndrome (EVC) also known as Chondroectodermal dysplasia or Mesoectodermal dysplasia, is a chondral and ectodermal dysplasia characterized by short ribs (chondrodystrophy), polydactyly, growth retardation, ectodermal and heart defects. It is a rare disease with approximately 300 cases reported worldwide. After birth, cardinal features are short stature, short ribs, polydactyly, dysplastic fingernails and teeth. Heart defects, especially abnormalities of atrial septation, occur in about 60% of cases. Cognitive and motor development is normal. This rare condition is inherited as an autosomal recessive trait with variable expression. Mutations of the EVC/EVC1 and EVC2 genes, located in a head to head configuration on chromosome 4p16, have been identified as causative. EVC belongs to the short rib-polydactyly group (SRP). The management of EVC is multidisciplinary. Management during the neonatal period is mostly symptomatic, involving treatment of the respiratory distress due to narrow chest and heart failure. Orthopedic follow-up is required to manage the bone deformities. Professional dental care should be considered for management of the oral manifestations. Prognosis is linked to the respiratory difficulties in the first months of life due to thoracic narrowness and possible heart defects. Prognosis of the final body height is difficult to predict.

Short Distance Channel Defect Intractions in Graphene Nanoribbon Field Effect Transistors

We have studied theoretically the channel defect interaction and for this we have used correlated nonradiative multiphonon theory in conjunction with the coulomb energy. We have presented the charge capture rate. To calculate the value of coulomb energy we have developed a quantum capacitive circuit considering the effect of the fringing electrical field distributed spatially in the dielectric. The calculated short distance charge capture rate for the channel subbands at room temperature revealed a significant correlation between the capture rate and singularity characteristics of the one dimensional density of states. Charge capture through the nonradiative multiphonon transition is responsible for the shortdistance interactions between the channel carriers and the interfacial dielectric defects that are typically located within a few nanometers of the dielectric channel interface.

TEMPLATE BASED DEFECT DETECTION OF FLEXIBLE PRINTED CIRCUIT

This study presented a research on machine vision inspection to define defects on flexible printed circuit (FPC). The images were subjected to image processing system where an elimination-subtraction method used. In this algorithm, 7 types of FPC defects defined and simulated in the system using Specimen 1 and processing time taken for both side inspection was 3.3s. Then, the commercial patent design of FPC was tested as specimen 2 to define short circuit defects on it. The processing time taken by this algorithm on specimen 2 was 0.28s. Comparison on manual inspection and machine vision implementation were carried out and greatly resulted on shorten inspection time to 59.7%. This result shows significant contribution in increasing the efficiency of FPC inspection process.

Hepatopulmonary Syndrome Is a Frequent Cause of Dyspnea in the Short Telomere Disorders

Telomere syndromes have their most common manifestation in idiopathic pulmonary fibrosis and emphysema. The short telomere defect in these patients may manifest systemically as bone marrow failure and liver disease. We sought to understand the causes of dyspnea in telomerase and telomere gene mutation carriers who have no parenchymal lung disease. Clinical and pathologic data were reviewed as part of a Johns Hopkins-based natural history study of short telomere syndromes including dyskeratosis congenita. Hepatopulmonary syndrome (HPS) was diagnosed in nine of 42 cases (21%). Their age at presentation was significantly younger than that of cases initially presenting with pulmonary fibrosis and emphysema (median, 25 years vs 55 years; P < .001). Cases had evidence of intra- and extrapulmonary arteriovascular malformations that caused shunt physiology. Nodular regenerative hyperplasia was the most frequent histopathologic abnormality, and it was seen in the absence of cirrhosis. Dyspnea and portal hypertension were progressive, and the median time to death or liver transplantation was 6 years (range, 4-10 years; n = 6). In cases that underwent liver transplantation, dyspnea and hypoxia improved, but pulmonary fibrosis subsequently developed. This report identifies HPS as a frequent cause of dyspnea in telomerase and telomere gene mutation carriers. While it usually precedes the development of parenchymal lung disease, HPS may also co-occur with pulmonary fibrosis and emphysema. Recognizing this genetic diagnosis is critical for management, especially in the lung and liver transplantation setting.

Modeling the influence of short wavelength defects in a railway track on the dynamic behavior of the Non-Suspended Masses

The motion of a railway vehicle on the rail running table, that is the area of the rail-head where the wheel is rolling, is a forced oscillation with a forcing excitation (track defects), and damping expressed by a random function. In the case of the Non-Suspended Masses the forces resulting from the excitation of short wavelength are large and have great effect on the rolling of the wheel. The track, is simulated as an elastic means with damping. In this paper the second order differential equation is presented for the case of a railway vehicle rolling on a railway track and its solution is presented for the Non-Suspended Masses of the vehicle. Furthermore the influence of the depth of the defect is examined and a sensitivity analysis of the influence of the Non-Suspended Masses and the track defects on the Acting loads is performed.

Abstract 397: Generation of Raf1 Mutant and Crispr-cas9 Corrected Isogenic iPSC-derived Cardiomyocytes to Model Hypertrophic Cardiomyopathy in Noonan Syndrome

Background: Hypertrophic cardiomyopathy (HCM) is a major cause of death in infants and children. Noonan Syndrome (NS), an autosomal dominant RASopathy disorder, is characterized by multiple defects, including short stature, facial dysmorphia, and congenital heart defects that include HCM. RASopathies are caused by germ-line mutations that affect the canonical RAS-MAPK pathway. Indeed, 95% of NS patients with a mutation in Raf1 , a gene that plays an integral role in this signaling cascade, exhibit HCM. However, the molecular mechanisms that elicit HCM in these patients remain poorly understood. Objective: To generate human NS Raf1 induced-pluripotent stem cells (iPSCs), correct the mutation by genome editing and subsequently differentiate isogenic iPSC lines into cardiomyocytes to characterize the molecular and genetic basis of HCM in NS patients. Results: We generated iPSCs from skin fibroblasts obtained from a NS pediatric patient with a single point mutation in the Raf1 gene. Using electroporation of four episomal vectors containing the Yamanaka factors, we obtained several iPSC clones with normal karyotypes and strong expression of pluripotent markers (Nanog, Oct4, Lin28, Sox2) as detected by RT-qPCR and immunofluorescence. We next corrected the mutation in the NS Raf1 iPSCs using genome editing CRISPR-Cas9 nickase technology. Correction of the Raf1 mutation was determined at the clonal level by PCR followed by Restriction Fragment Length Polymorphism and confirmed by Sanger sequencing. In addition, by inducing a Cas9 nickase-dependent frame shift mutation we also generated an isogenic iPSC line where Raf1 gene was knockout (KO), as demonstrated at the RNA level by RT-qPCR and at the protein level by Western Blot. We next differentiated these multiple iPSC lines (mutant, corrected and KO) into isogenic beating cardiomyocytes, with more &gt;98% of the cells positive for specific cardiomyocyte markers (α-actinin and cardiac TroponinT). Conclusion: We have successfully generated human NS Raf1 isogenic iPSC lines and corresponding cardiomyocytes. Currently, we are in progress of characterizing these cardiac cells to determine the molecular basis of NS-dependent HCM. Ultimately, our work should reveal new targets to treat HCM in NS patients.