A modeling framework and toolset for simulation and characterization of the cochlea within the auditory system

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Biological Engineering, 2011.Cataloged from PDF version of thesis.Includes bibliographical references (p. 50-53).Purpose: This research develops a modeling approach and an implementation toolset to simulate reticular lamina displacement in response to excitation at the ear canal and to characterize the cochlear system in the frequency domain. Scope The study develops existing physical models covering the outer, middle, and inner ears. The range of models are passive linear, active linear, and active nonlinear. These models are formulated as differential algebraic equations, and solved for impulse and tone excitations to determine responses. The solutions are mapped into tuning characteristics as a function of position within the cochlear partition. Objectives The central objective of simulation is to determine the characteristic frequency (CF)-space map, equivalent rectangular bandwidth (ERB), and sharpness of tuning (QERB) of the cochlea. The focus of this research is on getting accurate characteristics, with high time and space resolution. The study compares the simulation results to empirical measurements and to predictions of a model that utilizes filter theory and coherent reflection theory. Method We develop lumped and distributed physical models based on mechanical, acoustic, and electrical phenomena. The models are structured in the form of differential-algebraic equations (DAE), discretized in the space domain. This is in contrast to existing methods that solve a set of algebraic equations discretized in both space and time. The DAEs are solved using numerical differentiation formulas (NDFs) to compute the displacement of the reticular lamina and intermediate variables such as displacement of stapes in response to impulse and tone excitations at the ear canal. The inputs and outputs of the cochlear partition are utilized in determining its resonances and tuning characteristics. Transfer functions of the cochlear system with impulse excitation are calculated for passive and active linear models to determine resonance and tuning of the cochlear partition. Output characteristics are utilized for linear systems with tone excitation and for nonlinear models with stimuli of various amplitudes. Stability of the system is determined using generalized eigenvalues and the individual subsystems are stabilized based on their poles and zeros. Results The passive system has CF map ranging from 20 kHz at the base to 10 Hz at the apex of the cochlear partition, and has the strongest resonant frequency corresponding to that of the middle ear. The ERB is on the order of the CF, and the QERB is on the order of 1. The group delay decreases with CF which is in contradiction with findings from Stimulus Frequency Otoacoustic Emissions (SFOAE) experiments. The tuning characteristics of the middle ear correspond well to experimental observations. The stability of the system varies greatly with the choice of parameters, and number of space sections used for both the passive and active implementations. Implication Estimates of cochlear partition tuning based on solution of differential algebraic equations have better time and space resolution compared to existing methods that solve discretized set of equations. Domination of the resonance frequency of the reticular lamina by that of the middle ear rather than the resonant frequency of the cochlea at that position for the passive model is in contradiction with Bekesys measurements on human cadavers. Conclusion The methodology used in the thesis demonstrate the benefits of developing models and formulating the problem as differential-algebraic equations and solving it using the NDFs. Such an approach facilitates computation of responses and transfer functions simultaneously, studying stability of the system, and has good accuracy (controlled directly by error tolerance) and resolution.by Samiya Ashraf Alkhairy.M.Eng

Peran Pimpinan Pondok Pesantren dalam Meningkatkan KualitasDakwah Santri (Studi Deskriptif pada Ustadz Suherlan Pimpinan Pondok Pesantren Cipari Garut)

Pondok pesantren merupakan lembaga dakwah dan pendidikan Islam tertua di Indonesia. Keberadaan pondok pesantren tidak akan lepas dari peran dan gaya pendiri atau pimpinannya, karena segala kegiatan yang di jalankan oleh seorang pemimpin yang akan menentukan faktor sukses atau gagalnya pondok pesantren tersebut. Sama halnya dengan pondok pesantren Cipari di desa Sukarsa kecamatan Pangatikan Kabupaten Garut, keberadaannya tidak terlepas dari peran dan kepemimpinannya dalam meningkatkan kualitas dakwah pada santrinya di Pondok Pesantren Cipari Garut. Tujuan peneliti ini untuk mengetahui peran pimpinan dalam megarahkan perumusan kegiata dan implementasi program kegiatan dakwah santri,sehingga hasil implementasi program yang telah dilaksanakan dapat berjalan dengan baik di pondok pesantren. Peneliti ini bertolak dari pemikiran bahwa untuk mencapai tujuan, tertentu sangat diperlukan kerjakeras dan kerja sama antara pengurus danpimpinan. Dalam hal ini Peran pimpinan dalam meningkatkan dakwah santri adalah salah satu tujuan membimbing santri dalam meningkatkan kualitas dakwah santri yang bertujuan untuk menjadi insan kamil. Dan diharapkan mampu memberikan pelayanan yang menjadi tujuan generasi umat Islam Adapun teknik pengumpulan data yaitu, oberservasi, wawancara, dan dokumentasi. Metode yang digunakan adalah metode deskriptif dengan pendekatan kualitatif Hasil penelitian ini menemukan bahwa peran Pimpinan Pondok Pesantren dalam meningkatkan kualitas dakwah santri di Pondok Pesantren Cipari Garut yang bermula dari semangat tinggi pimpinannya untuk membangun dan juga berwawasan luas, sehingga dapat mempengaruhi masyarakat dan santri disekitarnya. Serta mampu mengelola kegiatan kemasyarakatan dan hasil yang telah dicapai menunjukkan bahwa peran pimpinan dalam meningkatkan kualitas dakwah santri mempunyai pendayagunaan, manfaat, dan kontribusi yang sangat penting. yakni sebagai pelaksana kegiatan-kegiatan pondok pesantren, membantu assatidz dalam menggantikan perannya mengisi acara dimasyarakat dalam bentuk ceramah maupun acara keagamaan lainya, sekaligus menjadi salah satu faktor memajukan dan menjaga kualitas pondok pesantren, sehingga adanya keuntungan terhadap santri sebagai pengaplikasian kemampuan dan kualitas santri, serta menambah pengetahuan dan pengalaman terhadap santri dalam kehidupan sehari-hari dan kehidupan bermasyarakat, sebagai ajang bakat santri, khidmatul assatidz, mendapatkan berkah dari kiyai dan pondok pesantren

Novel genetic associations with common variable immunodeficiency

Common variable immunodeficiency (CVID) is the most frequently encountered primary immunodeficiency disorder in clinical practice and is a cause of significant morbidity and mortality for patients. The main clinical features are hypogammaglobulinemia, recurrent infections and autoimmune disorders. Unlike the majority of primary immunodeficiency disorders, pinpointing a specific genetic association has been challenging. The objective of this work was to use next generation sequencing (NGS) technology in the form of whole exome sequencing (WES) to identify genetic associations with CVID. Candidate patients were selected based on parental consanguinity and availability of clinical specimens from them and their family members. Whole exome sequencing was performed and identified potential mutations which were confirmed by Sanger sequencing, followed by characterization of the novel mutations by immunological techniques. In Paper I, genetic analysis identified four novel CD27 mutations: homozygous missense mutations C96Y and R78W; heterozygous nonsense C10X; and compound heterozygous W8X-R107C resulting in a clinical phenotype of CD27 deficiency. In Paper II, whole exome sequencing revealed a novel W56X mutation in the RAC2 gene resulting in a CVID-like phenotype with prominent autoimmune disease. Newly identified abnormalities of neutrophil granules were identified by transmission electron microscopy. In Paper III, five novel mutations in the LRBA gene resulting in varied clinical phenotypes were presented in the context of a review of all published cases, thus providing a clinical summary. In conclusion, this work has shown the validity of employing whole exome sequencing in identifying genetic associations with CVID and CVID-like disease; and has provided a better overview of the diverse clinical phenotypes associated with mutations in CD27, RAC2 and LRBA and their resultant protein deficiencies

Peran Pimpinan Pondok Pesantren Dalam Meningkatkan Kualitas Dakwah Santri

The purpose of this research is to know the role (the region of influence), the role of leadership in directing the program, and the role of the leader in supervising the program of activities to improve the quality of preaching santri in Pondok Pesantren Cipari. The method used in this research is to use descriptive method, through qualitative approach The role of the leadership of Pondok Pesantren Cipari in directing the process of education in order to improve the quality of da'wah santri continues to be developed, it can be seen from the continuous activities of the santri to support the ability in da'wah and it is reflected in one of the activities of boarding school that is muhadharah routinely run every week. The role of the leadership of Pondok Pesantren Cipari in directing the program is seen in the organizing process which resulted in a formulation of organizational structure and delegation of authority and responsibility, a pattern that is built very distinctive, deliberation to consensus other than the leader also performs its function as a policy maker. The usual surveillance process at Pondok Pesantren Cipari by taking the course of the implementation of the activity, measuring its success and failure with the standard as it has been set. Penelitian ini dilakukan untuk bertujuan mengetahui peran (Wilayah pengaruh), peran pimpinan dalam mengarahkan program, serta peran pimpinan dalam mengawasi program kegiatan untuk meningkatkan kualitas dakwah santri di Pondok Pesantren Cipari.Metode yang digunakan dalam penelitian ini adalah menggunakan metode deskriptif, melalui pendekatan kualitatif. Peran pimpinan Pondok Pesantren Cipari dalam mengarahkan proses pendidikan guna meningkatkan kualitas dakwah santri terus dikembangkan, hal tersebut terlihat dari terus berjalannya kegiatan-kegiatan para santri untuk menunjang kemampuan dalam berdakwah dan hal tersebut tercermin dalam salah-satu kegiatan pondok pesantren yaitu muhadharah yang rutin dijalankan setiap minggunya. Peran pimpinan Pondok Pesantren Cipari dalam mengarahkan program terlihat pada proses pengorganisasian yang menghasilkan sebuah rumusan struktur organisasi dan pendelegasian wewenang dan tanggung jawab, pola yang dibangun sangat khas, musyawarah untuk mufakat selain pemimpin pun menjalankan fungsinya sebagai penentu kebijakan. Proses pengawasan yang biasa dilakukan di Pondok Pesantren Cipari dengan mengambil jalannya pelaksanaan kegiatan, mengukur keberhasilan dan kegagalannya dengan standar sebagaimana yang telah di tetapkan

Saudi Accented Arabic Voice Bank

AbstractThe aim of this paper is to present an Arabic speech database that represents Arabic native speakers from all the cities of Saudi Arabia. The database is called the Saudi Accented Arabic Voice Bank (SAAVB). Preparing the prompt sheets, selecting the right speakers and transcribing their speech are some of the challenges that faced the project team. The procedures that meet these challenges are highlighted. SAAVB consists of 1033 speakers speak in Modern Standard Arabic with a Saudi accent. The SAAVB content is analyzed and the results are illustrated. The content was verified internally and externally by IBM Cairo and can be used to train speech engines such as automatic speech recognition and speaker verification systems

Evaluation of large language models for discovery of gene set function

Gene set analysis is a mainstay of functional genomics, but it relies on manually curated databases of gene functions that are incomplete and unaware of biological context. Here we evaluate the ability of OpenAI's GPT-4, a Large Language Model (LLM), to develop hypotheses about common gene functions from its embedded biomedical knowledge. We created a GPT-4 pipeline to label gene sets with names that summarize their consensus functions, substantiated by analysis text and citations. Benchmarking against named gene sets in the Gene Ontology, GPT-4 generated very similar names in 50% of cases, while in most remaining cases it recovered the name of a more general concept. In gene sets discovered in 'omics data, GPT-4 names were more informative than gene set enrichment, with supporting statements and citations that largely verified in human review. The ability to rapidly synthesize common gene functions positions LLMs as valuable functional genomics assistants

Agammaglobulinaemia despite terminal B-cell differentiation in a patient with a novel LRBA mutation

Mutations in lipopolysaccharide-responsive vesicle trafficking, beach and anchor-containing protein (LRBA) cause immune deficiency and inflammation. Here, we are reporting a novel homozygous mutation in LRBA allele in 7-year-old Omani boy, born to consanguineous parents. He presented with type 1 diabetes, autoimmune haematological cytopenia, recurrent chest infections and lymphocytic interstitial lung disease. The patient was treated with CTLA4-Ig (abatacept) with good outcome every 2 weeks for a period of 3 months. He developed complete IgG deficiency, but remarkably, histological examination revealed germinal centres and plasma cells in lymphoid and inflamed lung tissue. Further charatecterisation showed these cells to express IgM but not IgG. This ex vivo analysis suggests that LRBA mutation confers a defect in class switching despite plasma cell formation