ON CONFORMAL QUASI HEMI-SLANT SUBMERSIONS FROM LORENTZIAN PARA SASAKIAN MANIFOLDS ONTP RIEMANNIAN MANIFOLDS

In the present article, our purpose is to define and study conformal quasi hemi-slant submersions (cqhs submersions, in short) from Lorentzian para Sasakian manifolds onto Riemannian manifolds. Its geometric properties are also investigated. Lastly, we give a non-trivial example for this type of submersio

Hybrid Approach for Resource Allocation in Cloud Infrastructure Using Random Forest and Genetic Algorithm

In cloud computing, the virtualization technique is a significant technology to optimize the power consumption of the cloud data center. In this generation, most of the services are moving to the cloud resulting in increased load on data centers. As a result, the size of the data center grows and hence there is more energy consumption. To resolve this issue, an efficient optimization algorithm is required for resource allocation. In this work, a hybrid approach for virtual machine allocation based on genetic algorithm (GA) and the random forest (RF) is proposed which belongs to a class of supervised machine learning techniques. The aim of the work is to minimize power consumption while maintaining better load balance among available resources and maximizing resource utilization. The proposed model used a genetic algorithm to generate a training dataset for the random forest model and further get a trained model. The real-time workload traces from PlanetLab are used to evaluate the approach. The results showed that the proposed GA-RF model improves energy consumption, execution time, and resource utilization of the data center and hosts as compared to the existing models. The work used power consumption, execution time, resource utilization, average start time, and average finish time as performance metrics

Intelligent Fault-Tolerant Mechanism for Data Centers of Cloud Infrastructure

Fault tolerance in cloud computing is considered as one of the most vital issues to deliver reliable services. Checkpoint/restart is one of the methods used to enhance the reliability of the cloud services. However, many existing methods do not focus on virtual machine (VM) failure that occurs due to the higher response time of a node, byzantine fault, and performance fault, and existing methods also ignore the optimization during the recovery phase. This paper proposes a checkpoint/restart mechanism to enhance reliability of cloud services. Our work is threefold: (1) we design an algorithm to identify virtual machine failure due to several faults; (2) an algorithm to optimize the checkpoint interval time is designed; (3) lastly, the asynchronous checkpoint/restart with log-based recovery mechanism is used to restart the failed tasks. The valuation results obtained using a real-time dataset shows that the proposed model reduces power consumption and improves the performance with a better fault tolerance solution compared to the nonoptimization method

Inhibition of IRGM establishes a robust antiviral immune state to restrict pathogenic viruses

The type I interferon (IFN) response is the major host arsenal against invading viruses. IRGM is a negative regulator of IFN responses under basal conditions. However, the role of human IRGM during viral infection has remained unclear. In this study, we show that IRGM expression is increased upon viral infection. IFN responses induced by viral PAMPs are negatively regulated by IRGM. Conversely, IRGM depletion results in a robust induction of key viral restriction factors including IFITMs, APOBECs, SAMHD1, tetherin, viperin, and HERC5/6. Additionally, antiviral processes such as MHC-I antigen presentation and stress granule signaling are enhanced in IRGM-deficient cells, indicating a robust cell-intrinsic antiviral immune state. Consistently, IRGM-depleted cells are resistant to the infection with seven viruses from five different families, including Togaviridae, Herpesviridae, Flaviviverdae, Rhabdoviridae, and Coronaviridae. Moreover, we show that Irgm1 knockout mice are highly resistant to chikungunya virus (CHIKV) infection. Altogether, our work highlights IRGM as a broad therapeutic target to promote defense against a large number of human viruses, including SARS-CoV-2, CHIKV, and Zika virus

Disparity in the DNA translocase domains of SWI/SNF and ISW2

An ATP-dependent DNA translocase domain consisting of seven conserved motifs is a general feature of all ATP-dependent chromatin remodelers. While motifs on the ATPase domains of the yeast SWI/SNF and ISWI families of remodelers are highly conserved, the ATPase domains of these complexes appear not to be functionally interchangeable. We found one reason that may account for this is the ATPase domains interact differently with nucleosomes even though both associate with nucleosomal DNA 17–18 bp from the dyad axis. The cleft formed between the two lobes of the ISW2 ATPase domain is bound to nucleosomal DNA and Isw2 associates with the side of nucleosomal DNA away from the histone octamer. The ATPase domain of SWI/SNF binds to the same region of nucleosomal DNA, but is bound outside of the cleft region. The catalytic subunit of SWI/SNF also appears to intercalate between the DNA gyre and histone octamer. The altered interactions of SWI/SNF with DNA are specific to nucleosomes and do not occur with free DNA. These differences are likely mediated through interactions with the histone surface. The placement of SWI/SNF between the octamer and DNA could make it easier to disrupt histone–DNA interactions

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

MECHANISMS OF CHROMATIN REMODELING BY ISWI FAMILY OF REMODELERS: A FUNCTIONAL AND STRUCTURAL INSIGHT INTO THE ROLE OF THE Itc1 SUBUNIT OF ISW2 REMODELING COMPLEX

ISWI type remodelers mobilize and space nucleosomes. These ATP-dependent remodeling complexes have a relatively small number of subunits (2-4) as compared to other classes of remodelers such as SWI/SNF, RSC and INO80/SWR-C. The accessory subunits of some of the ISWI remodelers from yeast have been shown to contact extensively extranucleosomal or linker DNA and appear to be involved in regulating the movement of nucleosomes along DNA. In the ISW2 complex, the Itc1 (accessory) and Isw2 (catalytic) subunits make up the minimal active complex. ISW2 moves mononucleosomes to the center of DNA as a function of the length of extranucleosomal DNA. This same property is also responsible for the nucleosome spacing activity of ISW2 observed in nucleosomal arrays. The Itc1 subunit has been shown to contact the linker DNA starting at the entry site of the nucleosome and extending over at least 59 bp of linker DNA. The role of the Itc1 subunit in regulating the remodeling activity of the ISW2 complex was investigated by deleting different regions of Itc1 and monitoring the effects on complex assembly, ATPase activity and nucleosome mobilization activities of ISW2. A key finding was that a domain of 322 amino acids at the C-terminus of Itc1 was crucial for regulating nucleosome movement. Deletion of this domain causes ISW2 to move nucleosomes from one end to the other of DNA without pausing or stopping at a central position unlike wild type (WT) ISW2. The missing domain appears to be responsible for sensing linker DNA length to stall or stop remodeling when linker DNA is shortened to certain lengths. Loss of another region of 122 amino acids near the C-terminus was found to adversely affect the processivity of the ISW2 complex. The regions of Itc1 contacting the different parts of linker DNA were mapped by site-directed DNA cross-linking and peptide mapping. The mapping data along with molecular modeling provided an idea of the spatial arrangement of Itc1 with linker DNA like that previously obtained for the Isw2 subunit. The domain of Itc1 that interacts with Isw2 and is required for complex assembly was also identified. Next, we have used an approach of arresting nucleosome movement by placing DNA gaps that block translocation to study the changes in contacts of Itc1 with linker DNA upon ATP hydrolysis and remodeling. Results from such experiments highlighted massive conformational changes in both Itc1 and Isw2, which cause bending of the extranucleosomal DNA and assist to pump it inside the nucleosome for DNA translocation. ISW1 complexes have a common catalytic subunit but different accessory subunits. Considering the vital role that accessory subunits play in modulating the catalytic activities of remodelers, a comparative analysis of the remodeling properties of ISW1a, ISW1b and ISW2 complexes with various nucleosomal substrates was done. The analysis revealed significant differences in substrate specificities and translocation mechanisms among these three remodelers. The most intriguing observation was that ISW1a requires two sites on DNA to initiate translocation, unlike other known remodeling complexes. One of the sites is at SHL2, signature of all remodelers characterized to date, whereas the other unique site is 10 bp from the nucleosome edge on the extranucleosomal DNA. These mechanistic differences exhibited by different complexes of the same family underscore the importance of auxiliary subunits as regulators of enzyme function

Micro-RNA and epigenetic factors regulatory network during Myelopoiesis

Mammalian hematopoiesis is a hierarchal developmental process, which starts with Hematopoietic Stem Cells (HSCs) in bone marrow and through progressive stages of lineage commitment and differentiation gives rise to different mature blood cell types. These blood types can be classified into myeloid and lymphoid lineages. Epigenetic factors (EFs) are a class of gene regulators that modulate chromatin signatures and also work in concert with other classes of regulators like transcription factors (TFs) and non-coding RNAs (ncRNAs), in regulating normal development process. Perturbations in the expression of these regulators have been linked to various developmental defects and diseases progression including hematopoiesis. We are interested in understanding the cross-talk among these crucial regulators during myeloid cell development and acute myeloid leukemia. Towards this, we have analyzed the mRNA expression profile during each stage of myeloid cell development. The differentially expressed EFs during each stage of development were integrated with a network formed using curated gene regulations from different databases and a potentially active EF sub-network for each stage of development was extracted. These active stage specific sub-networks were further analyzed to obtain the unexplored potential regulatory relationship between EFs and miRNAs in a stage specific manner. The stage specific regulatory network generation will provide a framework for further understanding and targeting crucial EFs in hematopoiesis or blood cell development, perturbation in which leads to leukemia

Potential role of TIGAR in OSCC: tumorigenesis and survival

Despite the improvement of treatment modalities, OSCC remains a prevalent disease in India and 50% of OSCC patients die within 5 years of disease detection. One of the major reasons for treatment failure is imbalances of metabolic profile in cancer. TIGAR (TP53-induced glycolysis and apoptosis regulator), is a p53-inducible protein that functions as fructose-2, 6-bisphosphatase and fructose-1, 6-bisphosphatase, reducing the glycolytic rate and promoting the Pentose Phosphate Pathway. Consistent with increased activation of the PPP, cells expressing TIGAR have higher NADPH levels and a concomitantly enhanced ability to regulate levels of cellular ROS and thus reduce oxidative stress. Apart from the metabolic function of TIGAR, it has another role in the survival of cancer. Recently found that TIGAR is upregulated in some cancer, the main focus of our proposed study is to find out the potential role of TIGAR in tumorigenesis and survival of OSCC. For this we are using OSCC cell line as well as primary OSCC sample, some our recent finding suggesting that TIGAR is upregulated in OSCC cell line as well as patient sample compared their respective control, and also found that TIGAR knockdown decreases cell viability and drug sensitivity. Our main focus is how TIGAR regulated OSCC cell survival and what mechanism behind this, for this we will use RNA-Seq in TIGAR KD cell and TIGAR OE cell and found that how many pathway or which gene is affecting when targeting TIGAR. So overall our findings prove that TIGAR has some role in the survival of OSCC