A Novel approach for optimization in Mathematical calculations using Vedic Mathematics Techniques

Vedic Mathematics is the name given to the ancient system of mathematics, or to be precise, a unique technique of calculations based on simple rules and principles with which any mathematical problem can be solved – be it arithmetic, algebra, geometry or trigonometry. The system is based on 16 Vedic sutras or aphorisms, which are actually word formulae describing natural ways of solving a whole range of mathematical problems. In this paper, we will be taking a few Vedic sutras. Akadhiken Purven (By one more than the one before), Nikhilam Navtashcharam Dashat (All from 9 and the last from 10) are two of them. NASA has adopted it fully in the realms of advanced robotics. Calculations that can be solved as quick as lightning are a great tool to adopt, but you wouldn’t want to teach it worldwide in the fear that you may churn out a generation of child geniuses that may threaten the intellectual status quo. The gift that the Hindus gave to the world, thousands of years ago, and that which is currently responsible for global silicon chip technology, was none other than the invention of zero and the use of the decimal point. We call our common numbers “Arabic Numerals” but really they extend back to the Hindu concept of creation and were known as “Bindu” or Unity. All Vedic Maths is based on the understanding of Unity Consciousness which means they utilize processes or Number Bases that correspond to 0, 10, 100, 1000, 10000, etc all of which add to 1. In light of the fact that the Vedas, literally “the illimitable storehouse of All Knowledge” came under 4 headings or categories like the Rig Veda, the Yajur Veda, the Sama Veda, and the Atharva Veda. Thus a Vedic Mathematician was also an astronomer, healer, and poet. It was a total system if you are out in the field and you need to tile a square floor that is, say 108 units square. How do you do it with mental ease? I think only of the excess “8”, saying how much is 108 more than my Base of 100. It is “8”. So we will merely add this “8” to the number in question “108” and tag on the squaring of this excess: 108 Squared = 108 + 8 / 8×8 = 116 / 64 = 11,664.Vedic mathematical methods are derived from ancient systems of computations, Compared to conventional mathematical methods, these are computationally faster and easier to perform. An application of Vedic mathematics can be effectively increased if it can make available to the beginners in various fields of study

Analysis of Effective Load Balancing Techniques in Distributed Environment

Computational approaches contribute a significance role in various fields such as medical applications, astronomy, and weather science, to perform complex calculations in speedy manner. Today, personal computers are very powerful but underutilized. Most of the computer resources are idle; 75% of the time and server are often unproductive. This brings the sense of distributed computing, in which the idea is to use the geographically distributed resources to meet the demand of high-performance computing. The Internet facilitates users to access heterogeneous services and run applications over a distributed environment. Due to openness and heterogeneous nature of distributed computing, the developer must deal with several issues like load balancing, interoperability, fault occurrence, resource selection, and task scheduling. Load balancing is the mechanism to distribute the load among resources optimally. The objective of this chapter is to discuss need and issues of load balancing that evolves the research scope. Various load balancing algorithms and scheduling methods are analyzed that are used for performance optimization of web resources. A systematic literature with their solutions and limitations has been presented. The chapter provides a concise narrative of the problems encountered and dimensions for future extension

Report of four novel variants in ASNS causing asparagine synthetase deficiency and review of literature

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145519/1/cga12275.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145519/2/cga12275_am.pd

Bain type of X‐linked syndromic mental retardation in a male with a pathogenic variant in HNRNPH2

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA binding proteins, which aid in maturation, stabilization, and transport of mRNA. They have a significant role in cellular nucleic acid metabolism. The hnRNPs alter gene expression and are linked to various neurodegenerative disorders and cancers. Previously, six unrelated girls with developmental delay, intellectual disability, and hypotonia were found to have de novo heterozygous pathogenic missense variants in HNRNPH2, located on the X chromosome. A gain‐of‐function effect was proposed for the variant and it was thought to be lethal in males as no surviving males were identified. We describe a family with two affected siblings, one male and one female, with a known pathogenic variant in HNRNPH2, possibly due to maternal germline mosaicism.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152580/1/ajmga61388.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152580/2/ajmga61388_am.pd

Homozygous deletion of exons 2 and 3 of NPC2 associated with Niemann–Pick disease type C

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134235/1/ajmga37794.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134235/2/ajmga37794-sup-0001-SuppData-S1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134235/3/ajmga37794_am.pd

Heterozygous ANKRD17 loss-of-function variants cause a syndrome with intellectual disability, speech delay, and dysmorphism

ANKRD17 is an ankyrin repeat-containing protein thought to play a role in cell cycle progression, whose ortholog in Drosophila functions in the Hippo pathway as a co-factor of Yorkie. Here, we delineate a neurodevelopmental disorder caused by de novo heterozygous ANKRD17 variants. The mutational spectrum of this cohort of 34 individuals from 32 families is highly suggestive of haploinsufficiency as the underlying mechanism of disease, with 21 truncating or essential splice site variants, 9 missense variants, 1 in-frame insertion-deletion, and 1 microdeletion (1.16 Mb). Consequently, our data indicate that loss of ANKRD17 is likely the main cause of phenotypes previously associated with large multi-gene chromosomal aberrations of the 4q13.3 region. Protein modeling suggests that most of the missense variants disrupt the stability of the ankyrin repeats through alteration of core structural residues. The major phenotypic characteristic of our cohort is a variable degree of developmental delay/intellectual disability, particularly affecting speech, while additional features include growth failure, feeding difficulties, non-specific MRI abnormalities, epilepsy and/or abnormal EEG, predisposition to recurrent infections (mostly bacterial), ophthalmological abnormalities, gait/balance disturbance, and joint hypermobility. Moreover, many individuals shared similar dysmorphic facial features. Analysis of single-cell RNA-seq data from the developing human telencephalon indicated ANKRD17 expression at multiple stages of neurogenesis, adding further evidence to the assertion that damaging ANKRD17 variants cause a neurodevelopmental disorder

Neurodevelopmental and Epilepsy Phenotypes in Individuals With Missense Variants in the Voltage-Sensing and Pore Domains of KCNH5

Background and Objectives KCNH5 encodes the voltage-gated potassium channel EAG2/Kv10.2. We aimed to delineate the neurodevelopmental and epilepsy phenotypic spectrum associated with de novo KCNH5 variants.Methods We screened 893 individuals with developmental and epileptic encephalopathies for KCNH5 variants using targeted or exome sequencing. Additional individuals with KCNH5 variants were identified through an international collaboration. Clinical history, EEG, and imaging data were analyzed; seizure types and epilepsy syndromes were classified. We included 3 previously published individuals including additional phenotypic details.Results We report a cohort of 17 patients, including 9 with a recurrent de novo missense variant p.Arg327His, 4 with a recurrent missense variant p.Arg333His, and 4 additional novel missense variants. All variants were located in or near the functionally critical voltage-sensing or pore domains, absent in the general population, and classified as pathogenic or likely pathogenic using the American College of Medical Genetics and Genomics criteria. All individuals presented with epilepsy with a median seizure onset at 6 months. They had a wide range of seizure types, including focal and generalized seizures. Cognitive outcomes ranged from normal intellect to profound impairment. Individuals with the recurrent p.Arg333His variant had a self-limited drug-responsive focal or generalized epilepsy and normal intellect, whereas the recurrent p.Arg327His variant was associated with infantile-onset DEE. Two individuals with variants in the pore domain were more severely affected, with a neonatal-onset movement disorder, early-infantile DEE, profound disability, and childhood death.Discussion We describe a cohort of 17 individuals with pathogenic or likely pathogenic missense variants in the voltage-sensing and pore domains of Kv10.2, including 14 previously unreported individuals. We present evidence for a putative emerging genotype-phenotype correlation with a spectrum of epilepsy and cognitive outcomes. Overall, we expand the role of EAG proteins in human disease and establish KCNH5 as implicated in a spectrum of neurodevelopmental disorders and epilepsy.</p

CPP-ZFN: A potential DNA-targeting anti-malarial drug

<p>Abstract</p> <p>Background</p> <p>Multidrug-resistant <it>Plasmodium </it>is of major concern today. Effective vaccines or successful applications of RNAi-based strategies for the treatment of malaria are currently unavailable. An unexplored area in the field of malaria research is the development of DNA-targeting drugs that can specifically interact with parasitic DNA and introduce deleterious changes, leading to loss of vital genome function and parasite death.</p> <p>Presentation of the hypothesis</p> <p>Advances in the development of zinc finger nuclease (ZFN) with engineered DNA recognition domains allow us to design and develop nuclease of high target sequence specificity with a mega recognition site that typically occurs only once in the genome. Moreover, cell-penetrating peptides (CPP) can cross the cell plasma membrane and deliver conjugated protein, nucleic acid, or any other cargo to the cytoplasm, nucleus, or mitochondria. This article proposes that a drug from the combination of the CPP and ZFN systems can effectively enter the intracellular parasite, introduce deleterious changes in its genome, and eliminate the parasite from the infected cells.</p> <p>Testing the hypothesis</p> <p>Availability of a DNA-binding motif for more than 45 triplets and its modular nature, with freedom to change number of fingers in a ZFN, makes development of customized ZFN against diverse target DNA sequence of any gene feasible. Since the <it>Plasmodium </it>genome is highly AT rich, there is considerable sequence site diversity even for the structurally and functionally conserved enzymes between <it>Plasmodium </it>and humans. CPP can be used to deliver ZFN to the intracellular nucleus of the parasite. Signal-peptide-based heterologous protein translocation to <it>Plasmodium</it>-infected RBCs (iRBCs) and different <it>Plasmodium </it>organelles have been achieved. With successful fusion of CPP with mitochondrial- and nuclear-targeting peptides, fusion of CPP with 1 more <it>Plasmodium </it>cell membrane translocation peptide seems achievable.</p> <p>Implications of the hypothesis</p> <p>Targeting of the <it>Plasmodium </it>genome using ZFN has great potential for the development of anti-malarial drugs. It allows the development of a single drug against all malarial infections, including multidrug-resistant strains. Availability of multiple ZFN target sites in a single gene will provide alternative drug target sites to combat the development of resistance in the future.</p

Hypomorphic Mutations in TONSL Cause SPONASTRIME Dysplasia

SPONASTRIME dysplasia is a rare, recessive skeletal dysplasia characterized by short stature, facial dysmorphism, and aberrant radiographic findings of the spine and long bone metaphysis. No causative genetic alterations for SPONASTRIME dysplasia have yet been determined. Using whole-exome sequencing (WES), we identified bi-allelic TONSL mutations in 10 of 13 individuals with SPONASTRIME dysplasia. TONSL is a multi-domain scaffold protein that interacts with DNA replication and repair factors and which plays critical roles in resistance to replication stress and the maintenance of genome integrity. We show here that cellular defects in dermal fibroblasts from affected individuals are complemented by the expression of wild-type TONSL. In addition, in vitro cell-based as-says and in silico analyses of TONSL structure support the pathogenicity of those TONSL variants. Intriguingly, a knock-in (KI) Tonsl mouse model leads to embryonic lethality, implying the physiological importance of TONSL. Overall, these findings indicate that genetic variants resulting in reduced function of TONSL cause SPONASTRIME dysplasia and highlight the importance of TONSL in embryonic development and postnatal growth.Peer reviewe