Study of effective methods of characterisation of magnetostriction and its fundamental effect on transformer core noise

Magnetostriction of core laminations is one of the main sources of transformer acoustic noise. The magnetostriction of grain oriented silicon steel is extremely sensitive to applied compressive stress. A measurement system using piezoelectric accelerometers has been designed and built. This was optimized for magnetostriction measurements under stress within the range of 10 MPa to -10 MPa on large as-cut sheets. This system was used for characterization of wide range of grain-oriented grades. Laboratories around the world are using many different methods of measurement of the magnetostrictive properties of electrical steel. In response to this level of interest, an international round robin exercise on magnetostriction measurement has been carried out and eight different magnetostriction-measuring systems have been compared. Results show a reasonable correlation between the different methods. In this study the influence of factors such as the domain refinement process, curvature, and geometry on the magnetostriction of 3% grain oriented silicon steel were investigated. The study shows that both laser scribing and mechanical scribing have a similar effect on the sample’s domain structure and would cause an increase in magnetostriction. A proposed domain model was used successfully to estimate the effect of scribing on magnetostriction. Correlation between magnetostriction of 3% grain oriented silicon steel with transformer vibration was investigated. It was shown that increasing the clamping pressure to 4Nm can decrease the out of plane vibration in the joint regions due to the increase of friction and reduction of air gap which reduces the air gap flux and consequently the Maxwell forces. Also it has been shown that the primary source for the differences between the vibration of the cores under the same magnetic excitation and clamping pressure in the measured cores is due to the differences in the magnetostriction characteristics of the grades of electrical steels. Correlations between the magnetostriction harmonics and the vibration of the cores have been determined

Comparison of Marginal Bone Loss in Simultaneous Versus Delayed Implant Placement Following Horizontal Ridge Augmentation with Autogenous Lateral Ramus Bone Block

Statement of the Problem: Alveolar ridge resorption after tooth extraction may interfere with optimal dental implant placement.Purpose: This study aimed to compare the marginal bone loss (MBL) and thickness of the buccal aspect of the augmented site in simultaneous versus delayed implant placement following lateral ramus horizontal ridge augmentation in the posterior mandible.Materials and Method: This prospective cohort study was conducted on patients who required horizontal bone augmentation of the posterior mandible using lateral ramus autogenous bone graft. Patients were divided into two groups of simultaneous implant placement (group 1) and delayed implant placement (group 2). Cone-beam computed tomography (CBCT) images were obtained before augmentation, at the time of implant placement, and 10 months later (6 months after implant loading). MBL and thickness of the buccal aspect were evaluated over time.Results: There were 18 patients in the group 1 and 16 patients in the group 2. Analysis of the CBCT scans demonstrated that the mean MBL was 1.21±0.35mm in the group 1 and 1.08±0.19mm in the group 2, with no significant difference between the two groups (p= 0.19). Thickness of the buccal aspect of the augmented site at the time of implant placement was 1.85±0.20mm in the group 1 and 2.16±0.29 mm in the group 2, with a significant difference (p< 0.001). However, data analysis regarding changes in the buccal plate thickness showed no significant difference between the two groups (p= 0.36).Conclusion: According to the results of this study, there was no significant difference in M-BL and post-operative changes in the thickness of the buccal aspect of the augmented sites with onlay lateral ramus bone blocks between simultaneous and delayed implant placement

Genome-wide scans provide evidence for positive selection of genes implicated in Lassa fever

Rapidly evolving viruses and other pathogens can have an immense impact on human evolution as natural selection acts to increase the prevalence of genetic variants providing resistance to disease. With the emergence of large datasets of human genetic variation, we can search for signatures of natural selection in the human genome driven by such disease-causing microorganisms. Based on this approach, we have previously hypothesized that Lassa virus (LASV) may have been a driver of natural selection in West African populations where Lassa haemorrhagic fever is endemic. In this study, we provide further evidence for this notion. By applying tests for selection to genome-wide data from the International Haplotype Map Consortium and the 1000 Genomes Consortium, we demonstrate evidence for positive selection in LARGE and interleukin 21 (IL21), two genes implicated in LASV infectivity and immunity. We further localized the signals of selection, using the recently developed composite of multiple signals method, to introns and putative regulatory regions of those genes. Our results suggest that natural selection may have targeted variants giving rise to alternative splicing or differential gene expression of LARGE and IL21. Overall, our study supports the hypothesis that selective pressures imposed by LASV may have led to the emergence of particular alleles conferring resistance to Lassa fever, and opens up new avenues of research pursuit

An Undiagnosed Case of Hypothalamic Hamartoma with a Rare Presentation.

Background. Hypothalamic hamartomas (HHs) are rare tumor-like malformations that may present with complex partial seizures refractory to anticonvulsants in adulthood. The condition may be misdiagnosed because of rarity. Case Presentation. We report a 25-year-old man with complaint of seizures presented by falling, tonic spasm of limbs, oral automatism, vocalization, and hypermotor activities. His seizures started at the age of one month and presented as eye deviation and upper limbs myoclonic jerk, followed by frequent seizures with variable frequency. The patient had delayed developmental milestones and was mentally retarded. He was hospitalized and underwent video-EEG monitoring and neuroimaging, and the diagnosis of HH was made. The patient became candidate for surgery after that. Conclusion. In this case, the underlying etiology of seizures was diagnosed after 25 years. HH is a rare condition and neurologists may encounter very small number of these cases during their practice. Therefore, they should consider it in patients who present with suspected signs and symptoms

Mining data from 1000 genomes to identify the causal variant in regions under positive selection

The human genome contains hundreds of regions in which the patterns of genetic variation indicate recent positive natural selection, yet for most of these the underlying gene and the advantageous mutation remain unknown. We recently reported the development of a method, Composite of Multiple Signals (CMS), that combines tests for multiple signals of natural selection and increases resolution by up to 100-fold

Lassa Fever in Post-Conflict Sierra Leone

Background: Lassa fever (LF), an often-fatal hemorrhagic disease caused by Lassa virus (LASV), is a major public health threat in West Africa. When the violent civil conflict in Sierra Leone (1991 to 2002) ended, an international consortium assisted in restoration of the LF program at Kenema Government Hospital (KGH) in an area with the world's highest incidence of the disease. Methodology/Principal Findings Clinical and laboratory records of patients presenting to the KGH Lassa Ward in the post-conflict period were organized electronically. Recombinant antigen-based LF immunoassays were used to assess LASV antigenemia and LASV-specific antibodies in patients who met criteria for suspected LF. KGH has been reestablished as a center for LF treatment and research, with over 500 suspected cases now presenting yearly. Higher case fatality rates (CFRs) in LF patients were observed compared to studies conducted prior to the civil conflict. Different criteria for defining LF stages and differences in sensitivity of assays likely account for these differences. The highest incidence of LF in Sierra Leone was observed during the dry season. LF cases were observed in ten of Sierra Leone's thirteen districts, with numerous cases from outside the traditional endemic zone. Deaths in patients presenting with LASV antigenemia were skewed towards individuals less than 29 years of age. Women self-reporting as pregnant were significantly overrepresented among LASV antigenemic patients. The CFR of ribavirin-treated patients presenting early in acute infection was lower than in untreated subjects. Conclusions/Significance: Lassa fever remains a major public health threat in Sierra Leone. Outreach activities should expand because LF may be more widespread in Sierra Leone than previously recognized. Enhanced case finding to ensure rapid diagnosis and treatment is imperative to reduce mortality. Even with ribavirin treatment, there was a high rate of fatalities underscoring the need to develop more effective and/or supplemental treatments for LF

Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever

Infection with Lassa virus (LASV) can cause Lassa fever, a haemorrhagic illness with an estimated fatality rate of 29.7%, but causes no or mild symptoms in many individuals. Here, to investigate whether human genetic variation underlies the heterogeneity of LASV infection, we carried out genome-wide association studies (GWAS) as well as seroprevalence surveys, human leukocyte antigen typing and high-throughput variant functional characterization assays. We analysed Lassa fever susceptibility and fatal outcomes in 533 cases of Lassa fever and 1,986 population controls recruited over a 7 year period in Nigeria and Sierra Leone. We detected genome-wide significant variant associations with Lassa fever fatal outcomes near GRM7 and LIF in the Nigerian cohort. We also show that a haplotype bearing signatures of positive selection and overlapping LARGE1, a required LASV entry factor, is associated with decreased risk of Lassa fever in the Nigerian cohort but not in the Sierra Leone cohort. Overall, we identified variants and genes that may impact the risk of severe Lassa fever, demonstrating how GWAS can provide insight into viral pathogenesis

Leveraging Genomic Signatures to Understand Human Disease: Applications in Infectious Disease and Cancer

Genomics has been transformative to the study of human evolution and disease. With the dropping cost and increased availability of genome sequencing, it is now possible to probe the genetic mediators of human disease at an unprecedented level. My own research grew out of earlier work on the genomic signatures of natural selection in humans. As an undergraduate, I investigated the evidence for recent positive selection in large-scale genomic data, identifying pathways that appear to be targeted by evolution and prioritizing promising candidate variants for functional follow-up. In medical school, I turned my attention to applying tools in genomics and evolution to the study of human disease. In this thesis, I present the results of that work applied to two major contributors to human morbidity and mortality: infectious disease and malignancy. Motivated by results from earlier work on genomic signals of recent adaptation in a West African population, I investigate genetic resistance to Lassa fever, a viral hemorrhagic disease endemic to West Africa. Focusing on a gene that is critical to Lassa infection and carries a signature of positive selection in the Yoruba population in Nigeria, I demonstrate that the same putative selected haplotype is present in other West African populations, but at different frequencies. Furthermore, I show evidence that the observed differences in frequency show correlation with the geographic distribution of Lassa virus and historical spread of the virus based on viral sequencing data. I test this haplotype for association with Lassa fever and demonstrate evidence of a protective effect. In a genome-wide association study for resistance to Lassa fever, I also identify preliminary genome-wide significant associations and promising variants for replication and follow-up. In the second part of this thesis, I focus on genomic study of human malignancy. I collaborate with a team to investigate the signatures of mutational forces in the cancer genome. We develop a novel computational framework to extract signatures from large-scale tumor sequencing data. Through this approach, we provide unbiased new estimates for the number and characteristics of the mutational processes that shape the cancer genome. We also investigate these signatures at an unprecedented level of resolution and show how they have the potential to reveal new mechanistic insights into the process of DNA damage repair and mutagenesis in cancer. Finally, we show how these signatures can reveal important clinical insights and identify subsets of tumors within the same tumor type that are dominated by different mutational processes. Our results are in stark contrast to the currently accepted model of mutational signatures in cancer, and have broad implications on our fundamental understanding of cancer biology and the future direction of the field. Although the diseases investigated here are diverse, the common theme underpinning my approach is to leverage tools in evolution and genomics to shed new light on the most devastating human diseases. Through this approach, I hope to extend our understanding of the biology of these disease processes, with implications on new therapeutic and public health interventions