A Novel Signal Processing Measure to Identify Exact and Inexact Tandem Repeat Patterns in DNA Sequences

The identification and analysis of repetitive patterns are active areas of biological and computational research. Tandem repeats in telomeres play a role in cancer and hypervariable trinucleotide tandem repeats are linked to over a dozen major neurodegenerative genetic disorders. In this paper, we present an algorithm to identify the exact and inexact repeat patterns in DNA sequences based on orthogonal exactly periodic subspace decomposition technique. Using the new measure our algorithm resolves the problems like whether the repeat pattern is of period P or its multiple (i.e., 2P, 3P, etc.), and several other problems that were present in previous signal-processing-based algorithms. We present an efficient algorithm of O(NLw logLw), where N is the length of DNA sequence and Lw is the window length, for identifying repeats. The algorithm operates in two stages. In the first stage, each nucleotide is analyzed separately for periodicity, and in the second stage, the periodic information of each nucleotide is combined together to identify the tandem repeats. Datasets having exact and inexact repeats were taken up for the experimental purpose. The experimental result shows the effectiveness of the approach

Face Recognition and Gender Classification using Principal Component Analysis

Face recognition is one of the most challenging areas in the field of computer vision. In this thesis, a photometric (view based) approach is used for face recognition and gender classification. There exist several algorithms to extract features such as Principal Component Analysis (PCA), Fisher Linear Discriminate Analysis (FLDA), Image principal component analysis (IPCA), and various others. Principal component analysis is used for the dimensional reduction and for the feature extraction. Two face databases are taken in which one database contains the face images of male and one contains face images of females. On the basis of Euclidean Distance classification of the gender is done. Comparison between Euclidean Distance and Mahalanobis Distance for face recognition is also done with different number of test images. This method is tested on FERET and IIT KanpurŒs database

An Epigenetic role for Tip60 in synaptic plasticity and neurodegenerative diseases

Age-associated cognitive decline and neurodegenerative disorders such as Alzheimers disease (AD) are associated with misregulation of synaptic plasticity linked genes; however the mechanisms underlying decline of such gene control during aging are unknown. Histone acetylation of chromatin promotes dynamic transcriptional responses in neurons that influence neuroplasticity critical for cognitive ability. Accordingly, aberrant changes to histone acetylation patterns in the aging brain epigenome are linked to memory loss. It is therefore critical to identify and study the histone acetyltransferases (HAT) that create such marks. One such promising candidate is Tip60, a HAT important for various cellular processes and also implicated in AD and shown by our laboratory to be critical in regulating neuronal processes linked to cognition. To explore a direct role for Tip60 in synaptic plasticity, here we explore the consequences of misregulating Tip60 HAT activity in the Drosophila neuromuscular junction (NMJ). The Drosophila NMJ is an extremely well characterized, highly tractable and valuable tool to study synaptic plasticity. In addition, many of the pathways present at the Drosophila NMJ are well conserved and homologous to the mammalian CNS. We show that the HAT dTip60 is concentrated both pre- and post-synaptically within the NMJ. Presynaptic targeted reduction of dTip60 HAT activity significantly increases synaptic bouton number that specifically affects type Is boutons while postsynaptic reduction results in significant loss of these boutons. The excess boutons demonstrate defects in neurotransmission function. Analysis using immunohistochemical staining to the MAP, futsch reveals a significant increase in the rearrangement of microtubule loop architecture that is required for bouton division. Our results are the first to demonstrate a causative role for the HAT dTip60 in the control of synaptic plasticity that is achieved, at least in part, via regulation of the synaptic microtubule cytoskeleton. We also show its post- synaptic role in the muscles and its function in retrograde signaling in addition to anterograde mechanisms. We show that postsynaptic loss of Tip60 HAT activity affects DLG localization, leads to decrease in GluRIIC subunit localization thus suggesting roles in activity dependent mechanisms. We also demonstrate its role in regulating genes involved in activity dependent synaptic plasticity and wingless pathway. Our ChIP-qPCR data suggests regulation of these genes via acetylation of learning and memory marks, H3K9, H4K12 and H4K16. We also report the functional interaction between HAT deficient Tip60 and hAPP at the NMJ, pre- and post-synaptically via the intracellular domain of APP (AICD), the molecule implicated in AD. Presynaptic expression of APP/Tip60 double mutants cause drastic increases in bouton numbers, and decrease in active zone synaptic function marker bruchpilot suggesting defects in neurotransmission. Conversely, postsynaptic expression of the APP/Tip60 double mutants leads to marked decrease in bouton numbers and absence of GluRIIC and decrease in GluRIIB and GluRIIA receptor subunits suggesting defects in signaling mechanisms. These findings have implications for dTip60 HAT dependant epigenetic mechanisms in neurodevelopment and neurodenerative diseases.Ph.D., Biology -- Drexel University, 201

Microarray Analysis Uncovers a Role for Tip60 in Nervous System Function and General Metabolism

Background: Tip60 is a key histone acetyltransferase (HAT) enzyme that plays a central role in diverse biological processes critical for general cell function; however, the chromatin-mediated cell-type specific developmental pathways that are dependent exclusively upon the HAT activity of Tip60 remain to be explored. Methods and Findings: Here, we investigate the role of Tip60 HAT activity in transcriptional control during multicellular development in vivo by examining genome-wide changes in gene expression in a Drosophila model system specifically depleted for endogenous dTip60 HAT function. Conclusions: We show that amino acid residue E431 in the catalytic HAT domain of dTip60 is critical for the acetylation of endogenous histone H4 in our fly model in vivo, and demonstrate that dTip60 HAT activity is essential for multicellular development. Moreover, our results uncover a novel role for Tip60 HAT activity in controlling neuronal specific gene expression profiles essential for nervous system function as well as a central regulatory role for Tip60 HAT function in general metabolism

RAPTOR: Recursive Abstractive Processing for Tree-Organized Retrieval

Retrieval-augmented language models can better adapt to changes in world state and incorporate long-tail knowledge. However, most existing methods retrieve only short contiguous chunks from a retrieval corpus, limiting holistic understanding of the overall document context. We introduce the novel approach of recursively embedding, clustering, and summarizing chunks of text, constructing a tree with differing levels of summarization from the bottom up. At inference time, our RAPTOR model retrieves from this tree, integrating information across lengthy documents at different levels of abstraction. Controlled experiments show that retrieval with recursive summaries offers significant improvements over traditional retrieval-augmented LMs on several tasks. On question-answering tasks that involve complex, multi-step reasoning, we show state-of-the-art results; for example, by coupling RAPTOR retrieval with the use of GPT-4, we can improve the best performance on the QuALITY benchmark by 20% in absolute accuracy