101 research outputs found
Detection and Defense Against Jellyfish Delay Variance Attack In MANETs
No full textME, CSEDMobile ad hoc networks comprise of mobile nodes communicating in multihop fashion without any infrastructure and are suitable for situations where infrastructure does not exist. These networks are vulnerable to many types of active, passive and DoS attacks. Jellyfish attack is a type of DoS attack which obeys protocol rules and is of 3 types: jellyfish reorder attack, jellyfish delay variance attack, jellyfish periodic dropping attack. Focus of thesis work is on evaluating the performance of network under the effect of jellyfish delay variance attack on AODV in MANETs and a scheme is proposed to detect and minimize the performance degradation caused by attacker. Simulations are carried out by taking different scenarios with varying node density to evaluate the effectiveness of proposed scheme and it is observed that performance of network improves in presence of scheme
Identifying novel disease genes in genetically undiagnosed individuals with Rett syndrome and related neurodevelopmental disorders
No full text© 2020 Simranpreet KaurRett Syndrome (RTT) is a severe neurodevelopmental disorder (NDD) resulting in severe cognitive and physical impairments. Despite being predominantly caused by pathogenic variants in the methyl-CpG-binding (MECP2) gene, between 3 – 15% of classic and atypical RTT individuals do not have a genetic diagnosis. Classic RTT individuals exhibit an apparently normal development until 6 to 18 months of age after which developmental regression occurs. Atypical RTT individuals have many features of classic RTT but do not meet all the specific diagnostic criteria. Recently, the classification of RTT has been expanded to include individuals with clinical features overlapping RTT and other NDDs, often referred to as RTT-like individuals. The clinical and genetic diagnosis for RTT-like individuals is further complicated due to the complexity of NDDs and there is an unmet need to provide a precise genetic diagnosis for these individuals.
Next generation sequencing (NGS) studies are continuously identifying hidden genetic links between relevant molecular pathways and RTT. Through whole genome sequencing (WGS), our lab had identified a de novo heterozygous missense variant [c.744C>A; (p.Asp248Glu)] in the motor domain of kinesin-3 family member 1A (KIF1A) in one classic RTT female. Single nucleotide heterozygous variants in KIF1A have been implicated in a number of severe neurological disorders, collectively known as KIF1A-associated neurological disorders (KANDs). KIF1A encodes a neuron-specific kinesin molecular motor protein essential for ATP-dependent anterograde axonal transport of synaptic cargos along microtubules. In order to determine additional RTT/RTT-like individuals with KIF1A variations, we collected further clinical and genetic information from our collaborators of 30 individuals with 18 different missense variants affecting the critical motor domain of KIF1A. After careful clinical assessment, we identified three additional individuals with different novel missense variants exhibiting overlapping RTT-like and KAND clinical features. In silico tools predicted all variants to affect proper protein folding and were predicted to be likely disease causing. In addition, in vitro functional analysis using the highly specific neurite tip accumulation and microtubule gliding assays, demonstrated all variants to have reduced microtubule based movement, suggesting these variants are indeed significantly pathogenic. Comparison of the clinical features of the remaining 27 KAND individuals with 16 variants in the KIF1A motor domain suggested that specific clinical features and phenotypic severity was largely dependent upon the location of the variant.
Using an NGS approach, we identified pathogenic MECP2 variants, previously missed by mainstream genetic testing, in seven RTT individuals including a case of a mosaic male. In addition, we found variants in two genes that are known to be associated with NDDs and RTT-like syndromes; Structural Maintenance of Chromosomes 1A [SMC1A; c.3576delA; p.(Val1193Serfs*2)] and SH3 and multiple ankyrin repeat domains 3 (SHANK3; c.2265+1G>A). This work continues to expand the genetic basis of RTT.
Through whole exome sequencing (WES), we have also identified an atypical RTT female with a heterozygous nonsense variant [c.3385C>T; p.(Arg1129*)] in Lysine Acetyltransferase 6A (KAT6A) that encodes a chromatin remodelling protein. Heterozygous protein truncating variants in this gene have been associated with KAT6A-related intellectual disability. Through various collaborations, we identified a further four individuals with KAT6A variants [c.3820G>T; p.(Glu1274*), c.3399_3400dup; p.(Lys1134Argfs*14), c.3377delC; p.(Ser1126Phefs*8) and c.3631_3632delGT; p.(Val1211*)] who had clinical symptoms overlapping with RTT/RTT-like individuals. Through systematic re-analysis of a reported cohort of 76 individuals with KAT6A-related intellectual disability we recognized two additional individuals exhibiting RTT-like clinical features with KAT6A variants [c.4254_4257del; p.(Glu1419Trpfs*12) and c.3661G>T; p.(Glu1221*)] . All the identified variants in the seven RTT-like individuals were clustered in the last exon of KAT6A and in silico analysis predicted the variants to cause a dominant-negative effect. These seven individuals exhibited clinical features overlapping between RTT and KAT6A-related intellectual disability that was previously unrecognized.
Using singleton WGS, a novel heterozygous nonsense variant in another chromatin regulator gene, Chromodomain helicase DNA-binding protein 8 [CHD8; c.5017C>T; p.(Arg1673*)] was identified in an atypical RTT individual. Heterozygous protein truncating variants in CHD8 have been implicated in NDDs including Autism Spectrum Disorders (ASDs). Functional analysis confirmed reduction in CHD8 protein levels in her fibroblasts, confirming the pathogenicity of the identified variant.
In another RTT-like female, a de novo heterozygous missense variant [c.271G>A; p.(Asp91Asn)] in the Eukaryotic Translation Elongation Factor 1 Alpha 2 (EEF1A2), involved in protein translation, was identified through singleton WES. This variant has been previously reported in a female with NDD. Interestingly, a single case with the same EEF1A2 variant [c.274G>A, p.(Ala92Thr)] has also been reported in a RTT-like female. Thus, our findings further established the casual association between EEF1A2 and a RTT-like phenotype.
In a RTT-like individual, a de novo large deletion at chromosome 9q34.11 (hg19:131,455,942-131,743,585) resulted in the loss of 13 genes, including the 3’ end of the coding sequence of SET Nuclear Proto-Oncogene (SET) and the 5’ end of the coding sequence of Nucleoporin-188 kDa (NUP188). The truncation of SET resulted in the loss of a highly conserved critical nucleosome assembly protein (NAP) domain crucial for assembly of nucleosomes and chromatin fluidity. Subsequent WES in the same individual identified a missense variant in NUP188 [c.3922C>T; p.(Arg1308Cys)] on the other allele. Preliminary functional studies in individual’s fibroblasts showed reduced NUP188 protein levels and enlarged nuclei, suggestive of perturbed NUP188 function. In this individual two genes, SET and NUP188, may be contributing to the affected individual’s phenotype.
Interestingly, a homozygous variant in a novel candidate disease gene, Potassium Channel Tetramerization Domain Containing 16 [KCTD16; c.937T>A; p.(Ser313Thr)], was also revealed in a classic RTT female. KCTD16 encodes an auxiliary subunit that associates with GABA-B receptor and regulates receptor response in an agonist concentration dependent manner. Although variants in the KCTD family of proteins have previously been reported in individuals with NDDs, defects specifically in KCTD16 are yet to be linked with any human disease. Our preliminary electrophysiological studies in Xenopus oocytes investigating perturbed GABA-B receptor kinetics in response to the KCTD16 variant [p.(Ser313Thr)] did not reveal any significant differences when compared to wild type, as well as a variant commonly found in the healthy population [p.(Asp160Asn)]. Despite this, we plan to continue these investigations in a mammalian Chinese Hamster Ovary (CHO) cell-based model to further evaluate the variant’s pathogenicity.
Overall, this study has provided functional evidence of variations affecting the motor domain of KIF1A in the pathophysiology of RTT/RTT-like disorders. In addition to identifying pathogenic variations in four known RTT-related genes (MECP2, SHANK3, SMC1A and EEF1A2), in this project we have further expanded the genetic landscape of RTT/RTT-like disorders to include variations in five additional genes (KAT6A, CHD8, SET, NUP188 and KCTD16). We recommend that the testing of these genes should be considered routinely while analysing NGS data in mutation negative RTT/ RTT-like individuals. The identification of additional members of key molecular pathways perturbed in RTT has further expanded our understanding of the underlying biology behind RTT, and this may pave the way for future targeted therapeutic options for RTT
Control of glyphosate-resistant giant ragweed (Ambrosia trifida L.) with premix of iodosulfuron /thiencarbazone applied alone or in tank-mixtures in no-till corn (Zea mays L.)
No full textThe objectives of this study were to evaluate the efficacy of a new premix of iodosulfuron (6%) /thiencarbazone (45%) applied alone or tank-mixed with 2,4-D, dicamba, glyphosate, or metribuzin in fall and/or early spring followed by pre-emergence (PRE) and post-emergence (POST) herbicide applications for control of glyphosate-resistant giant ragweed and their effect on corn yield. Field experiments were conducted in no-till corn fields infested with glyphosate-resistant giant ragweed (20 to 30 plants m─2) near Clay Center and McCool Junction, Nebraska, USA in 2013 and 2014, respectively. A premix of iodosulfuron /thiencarbazone applied alone or in split applications in fall and early spring controlled glyphosate-resistant giant ragweedThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author
Hints of auroral and magnetospheric polarized radio emission from the scallop-shell star 2MASS J05082729–2101444
No full textScallop-shell stars, a recently discovered class of young M dwarfs, show complex optical light curves that are characterized by periodic dips as well as other features that are stable over tens to hundreds of rotation cycles. The origin of these features is not well-understood. 2MASS J05082729−2101444 is a ∼25 Myr old scallop-shell star that was identified using TESS data; it has a photometric period of 6.73 h that has been attributed to rotation. Of the ∼50 recently confirmed scallop-shell stars, it is one of the few detected at radio frequencies between 1 and 8 GHz. We observed this rare system with the upgraded Giant Meterwave Radio Telescope at 575–720 MHz, covering 88% of the photometric period in each of the two observations scheduled almost a month apart in 2023. We detected approximately millijansky emission from the target in both epochs, with a significant circular polarization fraction: | V / I |∼20 − 50%. The 3.5-minute phase-folded light curves show unique variability in circular polarization. We detected an approximately hour-long helicity reversal during both epochs, and the reversals had similar amplitudes, lengths, and (possibly) occured at similar phases. These results suggest two emission components: The first is a persistent, moderately polarized component possibly ascribable to gyro-synchrotron emission driven by centrifugal breakout events. The second is a highly polarized, short burst-like component that is likely due to an electron cyclotron maser (ECM); it is indicative of auroral emission and is potentially responsible for the helicity reversal. To explain this, we discuss the different origins of the plasma responsible for the radio emission, including the possibility that the occulting material is acting as a plasma source. Future coordinated multifrequency radio and optical observations can further constrain the underlying scenario, as well as the magnetic geometry of the system, if we assume an ECM-like auroral emission
The role of macrophages in facilitating haematopoietic stem cell engraftment and reconstitution
No full textBiology and Control of Glyphosate-Resistant Giant Ragweed.
No full textGiant ragweed is a troublesome, early emerging, summer annual weed found throughout the eastern and midwestern corn and soybean growing regions of the United States. Since the emergence of giant ragweed varies at different locations, our first objective was to determine the emergence pattern of giant ragweed in Nebraska and how spring tillage influences emergence. Results of a two-year study suggested that giant ragweed emerged from late March until mid-June, with the majority of emergence ceasing by early May. Spring tillage could be used as an alternative method for managing glyphosate resistant giant ragweed.
Water stress can affect the growth and development of both crop plants and weeds. Thus, in our second objective, we hypothesized that drought conditions can result in a water deficit that can hinder giant ragweed growth and reproduction. Results suggested that the degree of water stress had more effect on plant growth and fecundity compared to the duration of water stress. Plants watered at a 10-day interval with 100% field capacity were still able to produce seeds, whereas only a few plants survived at 12.5% soil moisture content when irrigated at a 2-day interval.
Early emergence and a rapid growth rate make giant ragweed a competitive weed early in the season and reduce crop yields; therefore, in our third objective, we determined the early spring control of giant ragweed using a preplant herbicide. Several herbicide programs were investigated with preplant followed by pre-emergence (PRE) and post-emergence (POST) herbicides for controlling glyphosate-resistant giant ragweed
in glufosinate-resistant soybean. Results suggested that herbicide programs containing 2,4-D in preplant followed by an in-crop application of glufosinate provided 99% control of glyphosate-resistant giant ragweed and increased soybean yields.
Finally, since fall and early spring application of herbicides may influence giant ragweed emergence, our fourth objective was to determine the effect of fall and/or early spring application of a prepackaged mixture of iodosulfuron and thiencarbazone-methyl applied alone or tank-mixed with 2,4-D, dicamba, or metribuzin on glyphosate-resistant giant ragweed in no-till corn. Results suggested that the premix of iodosulfuron and thiencarbazone-methyl tank-mixed with 2,4-D, dicamba, or metribuzin followed by PRE and POST herbicide applications provided \u3e 95% control of glyphosate-resistant giant ragweed in no-till corn.
Advisor: Amit J. Jhal
A Framework to Study the Impact of Interventions on Social Isolation During Pandemics Using Multi-Agent Simulation
No full textThe spread of Coronavirus, widely known as COVID-19, has posed detrimental effects worldwide, affecting almost every primary sector. Due to its asymptomatic behavior and non-early diagnosis, government and health organizations implemented interventions such as physical distancing, lockdown, and quarantine, to mitigate the spread of the virus. Studies have shown that a connection exists between social isolation and health risks experienced by individuals. Thus, this research proposes an agent-based model to address the impact of varying interventions in our society. For simulation purposes, the SEIR model is followed, and agents are categorized into two classes based on their pace of movement, low and high mobility agents. These are further classified into four different states: susceptible, infected, recovered, and dead depending upon their changing health status. Their corresponding probabilities are determined, and the algorithm proceeds accordingly. Simulations of different scenarios before and during the COVID-19 are performed using multi-agents. Resulting outcomes are evaluated and analyzed, where agents may follow one or more interventions at a time. Various parameters are used in this research to imitate real-time physical situations while formulating the simulation environment. Some of these include the hospitals count, hospital capacity, transmission rate, and recovery time for agents in different states. Our model defines certain metrics based on the number of contacts an agent has with the other agents and the distance between the agents and its neighbors. Considering these multiple parameters and metrics enable the model to simulate varying conditions. For validation purposes, the simulation environment is made similar to the real-world society. Our model may benefit in deciding the mitigating factors in times of a similar pandemic or epidemic situations in the long term. Policymakers, health professionals, or researchers may extend this model and simulate the dissemination of ailments identical to this one
A Framework to Study the Impact of Interventions on Social Isolation During Pandemics Using Multi-Agent Simulation
No full textThe spread of Coronavirus, widely known as COVID-19, has posed detrimental effects worldwide, affecting almost every primary sector. Due to its asymptomatic behavior and non-early diagnosis, government and health organizations implemented interventions such as physical distancing, lockdown, and quarantine, to mitigate the spread of the virus. Studies have shown that a connection exists between social isolation and health risks experienced by individuals. Thus, this research proposes an agent-based model to address the impact of varying interventions in our society. For simulation purposes, the SEIR model is followed, and agents are categorized into two classes based on their pace of movement, low and high mobility agents. These are further classified into four different states: susceptible, infected, recovered, and dead depending upon their changing health status. Their corresponding probabilities are determined, and the algorithm proceeds accordingly. Simulations of different scenarios before and during the COVID-19 are performed using multi-agents. Resulting outcomes are evaluated and analyzed, where agents may follow one or more interventions at a time. Various parameters are used in this research to imitate real-time physical situations while formulating the simulation environment. Some of these include the hospitals count, hospital capacity, transmission rate, and recovery time for agents in different states. Our model defines certain metrics based on the number of contacts an agent has with the other agents and the distance between the agents and its neighbors. Considering these multiple parameters and metrics enable the model to simulate varying conditions. For validation purposes, the simulation environment is made similar to the real-world society. Our model may benefit in deciding the mitigating factors in times of a similar pandemic or epidemic situations in the long term. Policymakers, health professionals, or researchers may extend this model and simulate the dissemination of ailments identical to this one
UN PROCESO PARA LA IDENTIFICACION SISTEMATICA DE VARIACIONES GENOMICAS: APLICACIONES A LA MEDICINA DE PRECISION
No full textEl continuo descubrimiento de nueva información genómica genera un enorme volumen de datos relacionados con mutaciones genéticas que pueden ser relevantes para el diagnóstico clínico genómico de la enfermedad analizada. La identificación precisa y correcta de qué variaciones son las significativas a efectos de dicho diagnóstico es un problema de primera magnitud en el ámbito de la moderna Medicina de Precisión
Este proyecto enfrenta y propone una solución a ese problema: como determinar qué variaciones son las correctas, teniendo que seleccionarlas entre un conjunto extenso y diverso de fuentes de datos genómicos, con información muchas veces inconsistente, incompleta, presentados en formatos diversos, heterogénea y en definitiva, de complejo tratamiento tanto por el volumen de datos implicado como por la comentada heterogeneidad en la procedencia de los datos que hay que gestionar. Dicha heterogeneidad en los repositorios y la variedad de datos existentes generan conflictos durante la interpretación. El trabajo desarrollado en el proyecto unifica y sistematiza el proceso de identificación para asegurar la fiabilidad y precisión por su futura aplicación en la medicina clínica.
Para conseguirlo se utiliza la metodología SILE para la búsqueda, identificación, carga e explotación de los datos genómicos. El trabajo desarrollado ha explorado en profundidad la fase de identificación, mejorándolo de forma continua y analizando su viabilidad con dos casos prácticos que han demostrado la viabilidad del proceso de identificación. Se ha comprobado también que se cumplen con los criterios de calidad que la metodología SILE propone. El trabajo de Tesis fin de máster se ha aplicado a nivel práctico a la búsqueda e identificación de los SNPs (Single Nucleotide Polimorphism), que se refieren a Polimorfismos de Nucleótidos que están asociados a la enfermedad de Diabetes Mellitus Tipo 2 y Trombosis Venosa Profunda.
El proceso sistemático de identificación de variaciones genómicas es un paso adelante concreto y relevante en el ámbito del desarrollo del cuerpo de conocimiento asociado al diseño y gestión de Sistemas de Información Genómicos, líneas de I+D muy activa en el Centro de I+D en Métodos de Producción de Software de la Universidad Politécnica de Valencia, y conecta de forma precisa Ingeniería de Sistemas de Información, Ciencias de Datos Genómicos y aplicaciones a la Medicina de Precisión.The continuous discovery of new genomic information generates a huge volume of data related to genetic mutations that may be relevant to the clinical genomic diagnosis of diseases. The precise and correct identification of significant variations for the diagnosis of indicated purpose is a problem of first magnitude in the field of modern Precision Medicine
This project confronts and proposes a solution to this problem: how to determine which variations are the right ones, selecting them among an extensive and diverse set of genomic data sources, with information that is often inconsistent, incomplete, presented in diverse formats, heterogeneous and definitive, complex treatment both for the volume of data involved and for the aforementioned heterogeneity in the origin of the data that must be managed. This heterogeneity in the repositories and the variety of existing data generates conflicts during the interpretation. The work developed in the project unifies and systematizes the identification process to ensure reliability and accuracy for its future application in clinical medicine.
To achieve this, the SILE methodology is used to search, identify, load and exploit genomic data. The work developed has explored in depth the identification phase, improving it continuously and analyzing its viability with two practical cases that have demonstrated the viability of the identification process. It has also been verified that the quality criteria that the SILE methodology proposes are met. This Master's Thesis work has been applied at a practical level to search and identify SNPs (Single Nucleotide Polymorphism), which refer to Nucleotide Polymorphisms that are associated with the disease of Type 2 Diabetes Mellitus and Deep Vein Thrombosis.
The systematic process of identifying relevant genomic variations is a concrete and relevant step forward in the development of the body of knowledge associated with the design and management of Genomic Information Systems, very active R & D field in the R & D Center in Software Production Methods of the Polytechnic University of Valencia, and precisely connects Information Systems Engineering, Genomic Data Sciences and applications to Precision Medicine.Kaur, S. (2018). UN PROCESO PARA LA IDENTIFICACION SISTEMATICA DE VARIACIONES GENOMICAS: APLICACIONES A LA MEDICINA DE PRECISION. Universitat Politècnica de València. https://riunet.upv.es/handle/10251/115360TFG
The role of macrophages in facilitating haematopoietic stem cell engraftment and reconstitution
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