CHRONIC MYELOGENOUS LEUKEMIA: A REVIEW AND UPDATE OF CURRENT AND FUTURE THERAPY

Leukemia is a cancer of marrow and blood, which is a clonal myeloproliferative disease, characterized by the presence of oncogenic Philadelphia chromosome, formed by a reciprocal translocation between chromosomes 9 and 22, resulting in the novel chimeric oncoprotein BCR/ABL. Chronic leukemia typically progresses slowly and permits the growth of greater numbers of more developed cells. If the cell change takes place in a type of marrow cell that normally goes on to form red blood cells, some kinds of white blood cells and platelets, the leukemia is called myeloid. Therapy for chronic myeloid leukemia depends on the stage of CML patient. After diagnosis and confirmation of CML positive patient, treatment available for patients includes imatinib that is an early diagnosed treatment for CML but after some duration of time, it may lead to resistance to imatinib treatment. Dasatinib, nilotinib, bosutinib & ponatinib can be used for the treatment of CML as secondary treatments. Ponatinib is also found effective against T315i mutation patients. Omacetaxine mepesuccinate can be given with a mechanism of action independent of tyrosine kinase inhibition. Clinical trial for development of advanced therapy, which includes combination therapy and newer developed a treatment against CML are going on. It is required to develop better drug therapy, which will not cause genetical mutation and drug resistant. It is also required to find out thecause of resistance and what are the possible ways by which better therapy for CML is possible.Keywords: Philadelphia (Ph) chromosome, chronic myeloid leukemia, Imatinib, Tyrosine Kinase Inhibitor (TKI), Haematological Response (HR), Cytogenetic Response (CR), Molecular Responses (MR), Reverse Transcriptase Polymerase Chain Reaction (RTPCR), BCR-ABL gene, T315I mutation, Imatinib-Resistanc

Cobalt(III), nickel(II) and ruthenium(II) complexes of 1,10-phenanthroline family of ligands: DNA binding and photocleavage studies

DNA binding and photocleavage characteristics of a series of mixed-ligand complexes of the type [M(phen)2LL]n+ (where M = Co(III), Ni(II) or Ru(II), LL = 1,10-phenanthroline (phen), phenanthroline-dione (phen-dione) or dipyridophenazine (dppz) andn = 3 or 2) have been investigated in detail. Various physico-chemical and biochemical techniques including UV/Visible, fluorescence and viscometric titration, thermal denaturation, and differential pulse voltammetry have been employed to probe the details of DNA binding by these complexes; intrinsic binding constants (Kb) have been estimated under a similar set of experimental conditions. Analysis of the results suggests that intercalative ability of the coordinated ligands varies as dppz>phen>phen-dione in this series of complexes. While the Co(II) and Ru(II) complexes investigated in this study effect photocleavage of the supercoiled pBR 322 DNA, the corresponding Ni(II) complexes are found to be inactive under similar experimental conditions. Results of detailed investigations carried out inquiring into the mechanistic aspects of DNA photocleavage by [Co(phen)2(dppz)]3+ have also been reported

Isolation and characterization of altered root growth behavior and salinity tolerant mutants in rice

Generation, screening and isolating mutants for any developmental and adaptive traits plays a major role in plant functional genomics research. Identification and exploitation of mutants possessing contrasting root growth behavior and salinity tolerance in rice will help us to identify key genes controlling these traits and in turn will be useful for manipulating abiotic stress tolerance through tilling and genetic engineering in rice. In this study, we have screened about 1500 mutants (M2 generation) generated by treating an upland drought tolerant genotype Nagina 22 with Ethyl Methane Sulfonate (EMS), for their root growth behavior and salinity tolerance under hydroponic conditions. Six independent mutant lines possessing significantly shorter roots and three mutant lines exhibiting greater degree of salinity tolerance than the wild type plants were identified. The identified mutant lines were advanced to M5 generation to allow the mutants to reach homozygosity, and the fixed mutants were confirmed for their phenotype. One mutant namely N22-C-241-5-6 was found to possess significantly shorter roots than wild type N22, and it was also noticed that the mutant was devoid of root cap. Among the three salinity tolerant mutant lines identified, N22-C-334-3 was found to possess a greater degree of tolerance upto 250 mM Nacl stress at germination stage. These identified mutant lines can be used for further physiological, biochemical and molecular biology experiments to identify candidate gene(s) controlling root growth behavior and salinity tolerance in rice.Keywords: Rice, mutation, EMS, altered rood growth and salinity tolerant mutantAfrican Journal of Biotechnology Vol. 12(40), pp. 5852-585

Federated learning with hybrid differential privacy for secure and reliable cross-IoT platform knowledge sharing

The federated learning has gained prominent attention as a collaborative machine learning method, allowing multiple users to jointly train a shared model without directly exchanging raw data. This research addresses the fundamental challenge of balancing data privacy and utility in distributed learning by introducing an innovative hybrid methodology fusing differential privacy with federated learning(HDP-FL) Through meticulous experimentation on EMNIST and CIFAR-10 datasets, this hybrid approach yields substantial advancements, showcasing a noteworthy 4.22% and up to 9.39% enhancement in model accuracy for EMNIST and CIFAR-10, respectively, compared to conventional federated learning methods. Our adjustments to parameters highlighted how noise impacts privacy, showcasing the effectiveness of our hybrid DP approach in striking a balance between privacy and accuracy. Assessments across diverse FL techniques and client counts emphasized this trade-off, particularly in non-IID data settings, where our hybrid method effectively countered accuracy declines. Comparative analyses against standard machine learning and state-of-the-art FL approaches consistently showcased the superiority of our proposed model, achieving impressive accuracies of 96.29% for EMNIST and 82.88% for CIFAR-10. These insights offer a strategic approach to securely collaborate and share knowledge among IoT devices without compromising data privacy, ensuring efficient and reliable learning mechanisms across decentralized networks

Design and Analysis of Composite Leaf Spring

In the present scenario, reducing the weight is the major desire in automobile world. As the conventional steel leaf spring contributes some amount of weight with respect to the total weight of vehicle. So lots of researches are being developed for reduction of weight. This paper deals the reduction of weight in the conventional steel leaf spring with the composite leaf spring. For this purpose various composite materials such as E-glass, epoxy and jute are used in different proportion. This papers also compares the stress, deformation of conventional leaf steel spring with composite leaf spring while loading and unloading, thereby ensuring that the stiffness and efficiency is improved .The three dimensional model are analyzed in CATIA V5R20 and Ansys

Ultrasonic treatment of Cryptosporidium oocysts

Abstract The effect of 20 kHz ultrasound on the viability of Cryptosporidium oocysts was investigated. More than 90% of the dispersed Cryptosporidium oocysts could be deactivated in about 1.5 min of continuous sonication. In order to apply this technique to large quantities of contaminated water, quantitative filtration and redispersion of Cryptosporidium oocysts were investigated and found to be easily achievable. The estimated cost of sonication showed that the ultrasound treatment of Cryptosporidium oocysts contaminated water could be a very effective means of "deactivating" Cryptosporidium oocysts

A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and function

We report on a homozygous frameshift deletion in DDX59 (c.185del: p.Phe62fs*13) in a family presenting with orofaciodigital syndrome phenotype associated with a broad neurological involvement characterized by microcephaly, intellectual disability, epilepsy, and white matter signal abnormalities associated with cortical and subcortical ischemic events. DDX59 encodes a DEAD-box RNA helicase and its role in brain function and neurological diseases is unclear. We showed a reduction of mutant cDNA and perturbation of SHH signaling from patient-derived cell lines; furthermore, analysis of human brain gene expression provides evidence that DDX59 is enriched in oligodendrocytes and might act within pathways of leukoencephalopathies-associated genes. We also characterized the neuronal phenotype of the Drosophila model using mutant mahe, the homolog of human DDX59, and showed that mahe loss-of-function mutant embryos exhibit impaired development of peripheral and central nervous system. Taken together, our results support a conserved role of this DEAD-box RNA helicase in neurological function