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This article aims to provide approximate solutions for the non-linear collision-induced breakage equation using two different semi-analytical schemes, i.e., variational iteration method (VIM) and optimized decomposition method (ODM). The study also includes the detailed convergence analysis and error estimation for ODM in the case of product collisional ($K(\epsilon,\rho)=\epsilon\rho$) and breakage ($b(\epsilon,\rho,\sigma)=\frac{2}{\rho}$) kernels with an exponential decay initial condition. By contrasting estimated concentration function and moments with exact solutions, the novelty of the suggested approaches is presented considering three numerical examples. Interestingly, in one case, VIM provides a closed-form solution, however, finite term series solutions obtained via both schemes supply a great approximation for the concentration function and moments.

The non-linear collision-induced breakage equation has significant applications in particulate processes. Two semi-analytical techniques, namely homotopy analysis method (HAM) and accelerated homotopy perturbation method (AHPM) are investigated along with the well-known finite volume method (FVM) to comprehend the dynamical behavior of the non-linear system, i.e., the concentration function, the total number and the total mass of the particles in the system. The theoretical convergence analyses of the series solutions of HAM and AHPM are discussed. In addition, the error estimations of the truncated solutions of both methods equip the maximum absolute error bound. To justify the applicability and accuracy of these methods, numerical simulations are compared with the findings of FVM and analytical solutions considering three physical problems.

Cloud computing is an extremely important infrastructure used to perform tasks over processing units. Despite its numerous benefits, a cloud platform has several challenges preventing it from carrying out an efficient workflow submission. One of these is linked to task scheduling. An optimization problem related to this is the maximal determination of cloud computing scheduling criteria. Existing methods have been unable to find the quality of service (QoS) limits of users- like meeting the economic restrictions and reduction of the makespan. Of all these methods, the Heterogeneous Earliest Finish Time (HEFT) algorithm produces the maximum outcomes for scheduling tasks in a heterogeneous environment in a reduced time. Reviewed literature proves that HEFT is efficient in terms of execution time and quality of schedule. The HEFT algorithm makes use of average communication and computation costs as weights in the DAG. In some cases, however, the average cost of computation and selecting the first empty slot may not be enough for a good solution to be produced. In this paper, we propose different HEFT algorithm versions altered to produce improved results. In the first stage (rank generation), we execute several methodologies to calculate the ranks, and in the second stage, we alter how the empty slots are selected for the task scheduling. These alterations do not add any cost to the primary HEFT algorithm, and reduce the makespan of the virtual machines’ workflow submissions. Our findings suggest that the altered versions of the HEFT algorithm have a better performance than the basic HEFT algorithm regarding decreased schedule length of the workflow problems.

In this study, an attempt is made to investigate how the operational parameters such as capacitance, voltage, feed rate, and rotating speed affect the material removal rate, tool wear, overcut, and taper angle for micro-EDM drilling of aluminium 6061 utilizing brass C360 electrode. A novel Taguchi-GRA-CRITIC hybrid optimization methodology is used to obtain the optimal combination of micro-EDM drilling process parameters. The experiment was designed using the Taguchi L18 orthogonal array, and responses were recorded for each experiment. Grey Relational Analysis (GRA) is applied to improve the multi-response of the planned experiment. The weighting values corresponding to various responses are determined using CRITIC (criterion importance through intercriteria correlation) analysis. The hybrid methodology determines the best combination of process parameters for different responses. ANOVA was used to discover the most critical parameters. Finally, confirmation experiments were conducted with optimal parameters to identify improvement in grey relational grade over the initial parameters. The study's findings indicate that, compared to the initial process parameter setting, the grey relational grade (GRG) increased by 92.36% with the optimal parameter setting.

A performance comparison of the conventional slip ring induction motor (SRIM) drive and the recently inducted variable frequency drive (VFD) in the sugar industry, for sugarcane preparation (chopping/ shredding of sugarcane), is carried out to assess their effectiveness and to explore better electric drives for the application. These high inertial machines demand high starting torque and mitigating means to reduce surge load due to the impact load imposed on them. Though, both the drives meet the requirement but the SRIM drives are subjected to huge slip power loss, low power factor, unequal load sharing problem for coupled motors and high drop in rpm, whereas VFDs are subjected to the problems of input current harmonics, high dV/dt stress and common-mode voltage (CMV). In this paper, along with the performance comparison a three/four-level multilevel inverter (MLI) fed open-end winding induction motor (OEWIM) drive is also proposed as an improvement over the existing ones.

Drug oral absorption is a crucial concern, particularly when the medication is costly, poorly bioavailable, and administered for extended periods of time. Chemical substances known as "bioenhancers" are those that, when combined with pharmaceuticals, increase their bioavailability without having a synergistic impact on the drug itself. Toxicity, expense, poor bioavailability, and long-term medication administration all contribute to the need for bioenhancers, which aid in solving the majority of these issues. Piperine, also known as 1-peperoyl piperidine, is an aromatic alkaloid produced by the Piper species. Piperine alters the lipid milieu and membrane dynamics at the site of absorption to improve permeability. The molecular nature of piperine makes it appropriate for inhibiting enzymes. By blocking several metabolising enzymes, it increases the bioavailability of many medications, including carbamazepine, curcumin, ciprofloxacin, ampicillin, metronidazole, oxytetracycline, and many more. As a result, piperine, a potent inhibitor of medication metabolism, effectively increases absorption. The mechanism, metabolic inhibition, influence of structural alterations on activity, and medications that are bioenhanced by piperine are all explored in the review that follows. It offers insight into the use of piperine as a useful bioenhancer and the advantages of a bioenhanced drug formulation over one without one. Bioavailability enhancers are typically plant-based molecules that support the biological activity, bioavailability, or uptake of drugs in combination therapy. This review article finishes with discussing piperine's capacity to increase bioavailability. Keywords: Bioenhancers, Piperine, Oral absorption, Alkaloid.

The semi-analytical method obtains the solution for linear/nonlinear ODEs and PDEs in series form. This article presents a novel semi-analytical approach named Daftardar-Jafari method (DJM) to solve integro-partial differential equation such as breakage and nonlinear aggregation-breakage equations (ABE). Four test cases for the breakage equation are used to acquire closed form series solutions. Further, numerical findings such as number density and moments are compared with the analytical solutions to show the efficiency and accuracy of the method. Moreover, the DJM is employed to solve the well-known ABE, and truncated solutions are presented for the two test cases. In addition, absolute errors over various time periods are depicted in the form of tables.

Oxidative DNA damage is recognized by 8-oxoguanine (8-oxoG) DNA glycosylase 1 (OGG1), which excises 8-oxoG, leaving a substrate for apurinic endonuclease 1 (APE1) and initiating repair. Here, we describe a small molecule (TH10785) that interacts with the phenylalanine-319 and glycine-42 amino acids of OGG1, increases the enzyme activity 10-fold, and generates a previously undescribed beta,delta-lyase enzymatic function. TH10785 controls the catalytic activity mediated by a nitrogen base within its molecular structure. In cells, TH10785 increases OGG1 recruitment to and repair of oxidative DNA damage. This alters the repair process, which no longer requires APE1 but instead is dependent on polynucleotide kinase phosphatase (PNKP1) activity. The increased repair of oxidative DNA lesions with a small molecule may have therapeutic applications in various diseases and aging.

The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.

Collisional breakage in the particulate process has a lot of recent curiosity. We study the pure collisional breakage equation which is nonlinear in nature accompanied by locally bounded breakage kernel and collision kernel. The continuous equation is discretized using a finite volume scheme (FVS) and the weak convergence of the approximated solution towards the exact solution is analyzed for non-uniform mesh. The idea of the analysis is based on the weak $L^1$ compactness and a suitable stable condition on time step is introduced. Furthermore, theoretical error analysis is developed for a uniform mesh when kernels are taken in $W_{loc}^{1,\infty}$ space. The scheme is shown to be first-order convergent which is verified numerically for three test examples of the kernels.

This article deals with the convergence of finite volume scheme (FVS) for solving coagulation and multiple fragmentation equations having locally bounded coagulation kernel but singularity near the origin due to fragmentation rates. Thanks to the Dunford-Pettis and De La Vall$\acute{e}$e-Poussin theorems which allow us to have the convergence of numerically truncated solution towards a weak solution of the continuous model using a weak $L^1$ compactness argument. A suitable stable condition on time step is taken to achieve the result. Furthermore, when kernels are in $W^{1,\infty}_{loc}$ space, first order error approximation is demonstrated for a uniform mesh. It is numerically validated by attempting several test problems.

Currently, the majority of AML patients still die of their disease due to primary resistance or relapse toward conventional ROS- and DNA damage-inducing chemotherapy regimens. Herein, we explored the therapeutic potential to enhance chemotherapy response in AML, by targeting the ROS scavenger enzyme MutT homolog 1 (MTH1, NUDT1), which protects cellular integrity through prevention of fatal chemotherapy-induced oxidative DNA damage. We demonstrate that MTH1 is a potential druggable target expressed by the majority of AML patients and the inv(16)/KITD816Y AML mouse model mimicking the genetics of AML patients exhibiting poor response to standard chemotherapy (i.e. anthracycline & cytarabine). Strikingly, combinatorial treatment of inv(16)/KITD816Y AML cells with the MTH1 inhibitor TH1579 and ROS- and DNA damage-inducing standard chemotherapy induced growth arrest and incorporated oxidized nucleotides into DNA leading to significantly increased DNA damage. Consistently, TH1579 and chemotherapy synergistically inhibited growth of clonogenic inv(16)/KITD816Y AML cells without substantially inhibiting normal clonogenic bone marrow cells. In addition, combinatorial treatment of inv(16)/KITD816Y AML mice with TH1579 and chemotherapy significantly reduced AML burden and prolonged survival compared to untreated or single treated mice. In conclusion, our study provides a rationale for future clinical studies combining standard AML chemotherapy with TH1579 to boost standard chemotherapy response in AML patients. Moreover, other cancer entities treated with ROS- and DNA damage-inducing chemo- or radiation therapies might benefit therapeutically from complementary treatment with TH1579.

T cell-driven diseases account for considerable morbidity and disability globally and there is an urgent need for new targeted therapies. Both cancer cells and activated T cells have an altered redox balance, and up-regulate the DNA repair protein MTH1 that sanitizes the oxidized nucleotide pool to avoid DNA damage and cell death. Herein we suggest that the up-regulation of MTH1 in activated T cells correlates with their redox status, but occurs before the ROS levels increase, challenging the established conception of MTH1 increasing as a direct response to an increased ROS status. We also propose a heterogeneity in MTH1 levels among activated T cells, where a smaller subset of activated T cells does not upregulate MTH1 despite activation and proliferation. The study suggests that the vast majority of activated T cells have high MTH1 levels and are sensitive to the MTH1 inhibitor TH1579 (Karonudib) via induction of DNA damage and cell cycle arrest. TH1579 further drives the surviving cells to the MTH1[superscript low] phenotype with altered redox status. TH1579 does not affect resting T cells, as opposed to the established immunosuppressor Azathioprine, and no sensitivity among other major immune cell types regarding their function can be observed. Finally, we demonstrate a therapeutic effect in a murine model of experimental autoimmune encephalomyelitis. In conclusion, we show proof of concept of the existence of MTH1[superscript high] and MTH1[superscript low] activated T cells, and that MTH1 inhibition by TH1579 selectively suppresses pro-inflammatory activated T cells. Thus, MTH1 inhibition by TH1579 may serve as a novel treatment option against autoreactive T cells in autoimmune diseases, such as multiple sclerosis.

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy, exhibiting high levels of reactive oxygen species (ROS). ROS levels have been suggested to drive leukemogenesis and is thus a potential novel target for treating AML. MTH1 prevents incorporation of oxidized nucleotides into the DNA to maintain genome integrity and is upregulated in many cancers. Here we demonstrate that hematologic cancers are highly sensitive to MTH1 inhibitor TH1579 (karonudib). A functional precision medicine ex vivo screen in primary AML bone marrow samples demonstrated a broad response profile of TH1579, independent of the genomic alteration of AML, resembling the response profile of the standard-of-care treatments cytarabine and doxorubicin. Furthermore, TH1579 killed primary human AML blast cells (CD45+) as well as chemotherapy resistance leukemic stem cells (CD45+Lin−CD34+CD38−), which are often responsible for AML progression. TH1579 killed AML cells by causing mitotic arrest, elevating intracellular ROS levels, and enhancing oxidative DNA damage. TH1579 showed a significant therapeutic window, was well tolerated in animals, and could be combined with standard-of-care treatments to further improve efficacy. TH1579 significantly improved survival in two different AML disease models in vivo. In conclusion, the preclinical data presented here support that TH1579 is a promising novel anticancer agent for AML, providing a rationale to investigate the clinical usefulness of TH1579 in AML in an ongoing clinical phase I trial. Significance: The MTH1 inhibitor TH1579 is a potential novel AML treatment, targeting both blasts and the pivotal leukemic stem cells while sparing normal bone marrow cells.

The deoxycytidine analogue cytarabine (ara-C) remains the backbone treatment of acute myeloid leukaemia (AML) as well as other haematological and lymphoid malignancies, but must be combined with other chemotherapeutics to achieve cure. Yet, the underlying mechanism dictating synergistic efficacy of combination chemotherapy remains largely unknown. The dNTPase SAMHD1, which regulates dNTP homoeostasis antagonistically to ribonucleotide reductase (RNR), limits ara-C efficacy by hydrolysing the active triphosphate metabolite ara-CTP. Here, we report that clinically used inhibitors of RNR, such as gemcitabine and hydroxyurea, overcome the SAMHD1-mediated barrier to ara-C efficacy in primary blasts and mouse models of AML, displaying SAMHD1-dependent synergy with ara-C. We present evidence that this is mediated by dNTP pool imbalances leading to allosteric reduction of SAMHD1 ara-CTPase activity. Thus, SAMHD1 constitutes a novel biomarker for combination therapies of ara-C and RNR inhibitors with immediate consequences for clinical practice to improve treatment of AML.

When integrating to the power system, large wind farms pose stability and control issues. A thorough study is required to identify the potential problems and to develop measures to mitigate them. Although integration of high levels of wind power into an existing transmission system does not require a major redesign, it necessitates additional control and compensating equipment to enable recovery from severe system disturbances. This thesis investigates the use of a Static Synchronous Compensator (STATCOM) and SSSC along with wind farms for the purpose of stabilizing the grid voltage after grid-side disturbances such as a three phase short circuit fault, temporary trip of a wind turbine and sudden load changes. The DC voltage at individual wind turbine (WT) inverters is also stabilized to facilitate continuous operation of wind turbines during disturbances.

Altered oncogene expression in cancer cells causes loss of redox homeostasis resulting in oxidative DNA damage, e.g. 8-oxoguanine (8-oxoG), repaired by base excision repair (BER). PARP1 coordinates BER and relies on the upstream 8-oxoguanine-DNA glycosylase (OGG1) to recognise and excise 8-oxoG. Here we hypothesize that OGG1 may represent an attractive target to exploit reactive oxygen species (ROS) elevation in cancer. Although OGG1 depletion is well tolerated in non-transformed cells, we report here that OGG1 depletion obstructs A3 T-cell lymphoblastic acute leukemia growth in vitro and in vivo, validating OGG1 as a potential anti-cancer target. In line with this hypothesis, we show that OGG1 inhibitors (OGG1i) target a wide range of cancer cells, with a favourable therapeutic index compared to non-transformed cells. Mechanistically, OGG1i and shRNA depletion cause S-phase DNA damage, replication stress and proliferation arrest or cell death, representing a novel mechanistic approach to target cancer. This study adds OGG1 to the list of BER factors, e.g. PARP1, as potential targets for cancer treatment.

Indian English poetry has produced a number of literary movements; Aurobindonean School of Poetry, Ezekielen School of Poetry, Confessional School of Poetry, Subaltern School of Poetry and, above all, the Phrasal Movement for the spiritual whirlwind for Tom, Dick and Harry in general and the versifiers in particular in spite of the materialistic monarchy infecting the society. The Phrasal Movement in Indian English Poetry that runs wild from alpha and omega of the verses of the poet Arbind Kumar Choudhary speaks volumes about his gigantic poetic personality in and outside India.

The onset of inflammation is associated with reactive oxygen species and oxidative damage to macromolecules like 7,8-dihydro-8-oxoguanine (8-oxoG) in DNA. Because 8-oxoguanine DNA glycosylase 1 (OGG1) binds 8-oxoG and because Ogg1-deficient mice are resistant to acute and systemic inflammation, we hypothesized that OGG1 inhibition may represent a strategy for the prevention and treatment of inflammation. We developed TH5487, a selective active-site inhibitor of OGG1, which hampers OGG1 binding to and repair of 8-oxoG and which is well tolerated by mice. TH5487 prevents tumor necrosis factor-alpha-induced OGG1-DNA interactions at guanine-rich promoters of proinflammatory genes. This, in turn, decreases DNA occupancy of nuclear factor kappa B and proinflammatory gene expression, resulting in decreased immune cell recruitment to mouse lungs. Thus, we present a proof of concept that targeting oxidative DNA repair can alleviate inflammatory conditions in vivo.

The dCTP pyrophosphatase 1 (dCTPase) is a nucleotide pool "housekeeping" enzyme responsible for the catabolism of canonical and noncanonical nucleoside triphosphates (dNTPs) and has been associated with cancer progression and cancer cell sternness. We have identified a series of piperazin-1-ylpyridazines as a new class of potent dCTPase inhibitors. Lead compounds increase dCTPase thermal and protease stability, display outstanding selectivity over related enzymes and synergize with a cytidine analogue against leukemic cells. This new class of dCTPase inhibitors lays the first stone toward the development of drug-like probes for the dCTPase enzyme.

Glioblastoma multiforme (GBM) is an aggressive form of brain cancer with poor prognosis. Cancer cells are characterized by a specific redox environment that adjusts metabolism to its specific needs and allows the tumor to grow and metastasize. As a consequence, cancer cells and especially GBM cells suffer from elevated oxidative pressure which requires antioxidant-defense and other sanitation enzymes to be upregulated. MTH1, which degrades oxidized nucleotides, is one of these defense enzymes and represents a promising cancer target. We found MTH1 expression levels elevated and correlated with GBM aggressiveness and discovered that siRNA knock-down or inhibition of MTH1 with small molecules efficiently reduced viability of patient-derived GBM cultures. The effect of MTH1 loss on GBM viability was likely mediated through incorporation of oxidized nucleotides and subsequent DNA damage. We revealed that MTH1 inhibition targets GBM independent of aggressiveness as well as potently kills putative GBM stem cells in vitro. We used an orthotopic zebrafish model to confirm our results in vivo and light-sheet microscopy to follow the effect of MTH1 inhibition in GBM in real time. In conclusion, MTH1 represents a promising target for GBM therapy and MTH1 inhibitors may also be effective in patients that suffer from recurring disease., QC 20171103Erratum: 2020 Oncotarget11(8), pp. 827 Scopus: 2-s2.0-85082722694

The cytostatic deoxycytidine analog cytarabine (ara-C) is the most active agent available against acute myelogenous leukemia (AML). Together with anthracyclines, ara-C forms the backbone of AML treatment for children and adults'. In AML, both the cytotoxicity of ara-C in vitro and the clinical response to ara-C therapy are correlated with the ability of AML blasts to accumulate the active metabolite ara-C triphosphate (ara-CTP)(2-5), which causes DNA damage through perturbation of DNA synthesis(6). Differences in expression levels of known transporters or metabolic enzymes relevant to ara-C only partially account for patient-specific differential ara-CTP accumulation in AML blasts and response to ara-C treatment(7-9). Here we demonstrate that the deoxynucleoside triphosphate (dNTP) triphosphohydrolase SAM domain and HD domain 1 (SAMHD1) promotes the detoxification of intracellular ara-CTP pools. Recombinant SAMHD1 exhibited ara-CTPase activity in vitro, and cells in which SAMHD1 expression was transiently reduced by treatment with the simian immunodeficiency virus (SIV) protein Vpx were dramatically more sensitive to ara-C-induced cytotoxicity. CRISPR-Cas9-mediated disruption of the gene encoding SAMHD1 sensitized cells to ara-C, and this sensitivity could be abrogated by ectopic expression of wild-type (WT), but not dNTPase-deficient, SAMHD1. Mouse models of AML lacking SAMHD1 were hypersensitive to ara-C, and treatment ex vivo with Vpx sensitized primary patient derived AML blasts to ara-C. Finally, we identified SAMHD1 as a risk factor in cohorts of both pediatric and adult patients with de novo AML who received ara-C treatment. Thus, SAMHD1 expression levels dictate patient sensitivity to ara-C, providing proof-of-concept that the targeting of SAMHD1 by Vpx could be an attractive therapeutic strategy for potentiating ara-C efficacy in hematological malignancies., Funding: We are grateful to M. Wickstrom, N. Eissler and L. Elfman for consulting and assistance with xenotransplantation. We thank S. Olsson and M. Gustafsson for assistance with animal work. We would like to thank I. Bodin for help with paraffin-embedding and processing of tumor tissue and A. Bjorklund for assistance with primary AML samples. We acknowledge M. Nordenskjold and S. Eriksson for laboratory assistance, D. Gavhed and K. Edfeldt for administrative assistance. We thank D. Trono for the gift of the pMD.G plasmid. We would like to thank J. Cinatl for initial discussions. We would like to express our gratitude to NCI's Office of Cancer Genomics (OCG), The Cancer Genome Atlas (TCGA) and Therapeutically Applicable Research To Generate Effective Treatments initiative (TARGET) for granting public access to their AML databases, and to the Broad Institute for access to the Cancer Therapeutics Response Portal (CTRP). This work was supported by grants from the Swedish Children's Cancer Foundation (TJ2016-0040 (to N.H.); 2015-0005 (to J.-I.H.); PR2015-0009 (to D.G.); and PR2013-0002 and PR2014-0048 (both to T.H.)), the Swedish Cancer Society (CAN 2016/837 to J.W.; CAN 2014/814 to S.L.; CAN 2015/768 to D.G.; CAN 2013/396 to J.-I.H.; and CAN 2012/770 and CAN 2015/255 to T.H.), the Swedish Research Council (2014-1839 to M.U.; 2015-02498 to S.L.; 2012-2037 to D.G.; and 2012-5935 and 2013-3791 to T.H.), Radiumhemmet's Research Foundations (154242 to G.R. and 144063 to D.G.), the Knut and Alice Wallenberg Foundation (KAW2014.0273 to T.H.), the Swedish Pain Relief Foundation (SSF/01-05 to T.H.), the Torsten and Ragnar Soderberg Foundation (to T.H.), the David and Astrid Hagelen Foundation (C24702193 to B.D.G.P.) and the Stockholm County Council (ALF project) (20150353 to S.L. and 20150016 to J.-I.H.). This work was supported by the German Research Foundation (DFG) (SCHA1950/1-1 to T.S.) and partially through the Federal Ministry of Education and Research of Germany (BMB

Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.

We present observations of a confined M4.0 flare from NOAA 11302 on 2011 September 26. Observations at high temporal, spatial, and spectral resolution from Solar Dynamics Observatory, Reuven Ramaty High Energy Solar Spectroscopic Imager, and Nobeyama Radioheliograph enabled us to explore the possible triggering and energy release processes of this flare despite its very impulsive behavior and compact morphology. The flare light curves exhibit an abrupt rise of non-thermal emission with co-temporal hard X-ray (HXR) and microwave (MW) bursts that peaked instantly without any precursor emission. This stage was associated with HXR emission up to 200 keV that followed a power law with photon spectral index ($\delta$) $\sim$3. Another non-thermal peak, observed 32 s later, was more pronounced in the MW flux than the HXR profiles. Dual peaked structure in the MW and HXR light curves suggest a two-step magnetic reconnection process. Extreme ultraviolet (EUV) images exhibit a sequential evolution of the inner and outer core regions of magnetic loop system while the overlying loop configuration remained unaltered. Combined observations in HXR, (E)UV, and H$\alpha$ provide support for flare models involving interaction of coronal loops. The magnetograms obtained from Helioseismic and Magnetic Imager (HMI) reveal the emergence of magnetic flux which started $\sim$5 hr before the flare. However, the more crucial changes in the photospheric magnetic flux occurred about 1 minute prior to the flare onset with opposite polarity magnetic transients appearing at the early flare location within the inner core region. The spectral, temporal, and spatial properties of magnetic transients suggest that the sudden changes in the small-scale magnetic field have likely triggered the flare by destabilizing the highly sheared pre-flare magnetic configuration., Comment: 18 pages, Accepted for publication in ApJ

A sensor network is one of the critical networks that is based on hardware components as well the energy parameters. Because of this, such network requires the optimization in all kind communication to improve the network life. In case of underwater sensor network, the criticality of network is also increased because of the random floating movement of the nodes. In this work, a composition of the multicast or broadcast communication is presented by the generation of aggregative path. The presented work is about to define a new chain based aggregative routing approach to provide the effective communication over the network. In this work, an effective aggregative path is suggested under the different parameters of energy, distance and congestion analysis. Based on these parameters a trustful aggregative route will be generated so that the network life will be improved., Comment: 4 pages,1 figure

An understanding of how individuals shape and impact the evolution of society is vastly limited due to the unavailability of large-scale reliable datasets that can simultaneously capture information regarding individual movements and social interactions. We believe that the popular Indian film industry, 'Bollywood', can provide a social network apt for such a study. Bollywood provides massive amounts of real, unbiased data that spans more than 100 years, and hence this network has been used as a model for the present paper. The nodes which maintain a moderate degree or widely cooperate with the other nodes of the network tend to be more fit (measured as the success of the node in the industry) in comparison to the other nodes. The analysis carried forth in the current work, using a conjoined framework of complex network theory and random matrix theory, aims to quantify the elements that determine the fitness of an individual node and the factors that contribute to the robustness of a network. The authors of this paper believe that the method of study used in the current paper can be extended to study various other industries and organizations., Comment: 39 pages, 12 figures, 14 tables

The sunspot penumbra comprises numerous thin, radially elongated filaments that are central for heat transport within the penumbra, but whose structure is still not clear. To investigate the fine-scale structure of these filaments, we perform a depth-dependent inversion of spectropolarimetric data of a sunspot very close to solar disk center obtained by Hinode (SOT/SP). We have used a recently developed spatially coupled 2D inversion scheme which allows us to analyze the fine structure of individual penumbral filaments up to the diffraction limit of the telescope. Filaments of different sizes in all parts of penumbra display very similar magnetic field strengths, inclinations and velocity patterns. The similarities allowed us to average all these filaments and to extract the physical properties common to all of them. This average filament shows upflows associated with an upward pointing field at its inner, umbral end and along its axis, downflows along the lateral edge and strong downflows in the outer end associated with a nearly vertical, strong and downward pointing field. The upflowing plasma is significantly hotter than the downflowing plasma. The hot, tear-shaped head of the averaged filament can be associated with a penumbral grain. The central part of the filament shows nearly horizontal fields with strengths of ~1kG. The field above the filament converges, whereas a diverging trend is seen in the deepest layers near the head of the filament. We put forward a unified observational picture of a sunspot penumbral filament. It is consistent with such a filament being a magneto-convective cell, in line with recent MHD simulations. The uniformity of its properties over the penumbra sets constraints on penumbral models and simulations. The complex and inhomogeneous structure of the filament provides a natural explanation for a number of long-running controversies in the literature., Comment: 19 pages; 12 figures; accepted for publication in A&A

Background: Chemotherapy-induced reduction in tumor load is a function of apoptotic cell death, orchestrated by intracellular caspases. However, the effectiveness of these therapies is compromised by mutations affecting specific genes, controlling and/or regulating apoptotic signaling. Therefore, it is desirable to identify novel pathways of cell death, which could function in tandem with or in the absence of efficient apoptotic machinery. In this regard, recent evidence supports the existence of a novel cell death pathway termed autophagy, which is activated upon growth factor deprivation or exposure to genotoxic compounds. The functional relevance of this pathway in terms of its ability to serve as a stress response or a truly death effector mechanism is still in question; however, reports indicate that autophagy is a specialized form of cell death under certain conditions. Methodology/Principal Findings: We report here the simultaneous induction of non-canonical autophagy and apoptosis in human cancer cells upon exposure to a small molecule compound that triggers intracellular hydrogen peroxide (H2O2) production. Whereas, silencing of beclin1 neither inhibited the hallmarks of autophagy nor the induction of cell death, Atg 7 or Ulk1 knockdown significantly abrogated drug-induced H2O2-mediated autophagy. Furthermore, we provide evidence that activated extracellular regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) are upstream effectors controlling both autophagy and apoptosis in response to elevated intracellular H2O2. Interestingly, inhibition of JNK activity reversed the increase in Atg7 expression in this system, thus indicating that JNK may regulate autophagy by activating Atg7. Of note, the small molecule compound triggered autophagy and apoptosis in primary cells derived from patients with lymphoma, but not in non-transformed cells. Conclusions/Significance: Considering that loss of tumor suppressor beclin 1 is associated with neoplasia, the ability, Singapore. Biomedical Research Council, Singapore. Ministry of Education

A major flare (of class X3.4) occurred on 13 December 2006 in the active region NOAA 10930. The energy released during flares is also known to induce acoustic oscillations in the Sun. Here, we analyze the line-of-sight velocity patterns in this active region during the X3.4 flare using the Dopplergrams obtained by GONG instrument. We have also analyzed the disk-integrated velocity observations of the Sun obtained by GOLF instrument onboard SOHO spacecraft as well as full-disk collapsed velocity signals from GONG observations during this flare to study any possible connection between the flare related changes seen in the local and global velocity oscillations in the Sun. We apply wavelet transform to the time series of the localized velocity oscillations as well as the global velocity oscillations in the Sun spanning the flare event. The line-of-sight velocity shows significant enhancement in some localized regions of the penumbra of this active region during the flare. The affected region is seen to be away from the locations of the flare ribbons and the hard X-ray footpoints. The sudden enhancement in this velocity seems to be caused by the Lorentz force driven by the "magnetic jerk" in the localized penumbral region. Application of wavelet analysis to these flare induced localized seismic signals show significant enhancement in the high-frequency domain (5-8 mHz) and a feeble enhancement in the p-mode oscillations (2-5 mHz) during the flare. On the other hand, the wavelet analysis of GOLF velocity data and the full-disk collapsed GONG velocity data spanning the flare event indicate significant post-flare enhancements in the high-frequency global velocity oscillations in the Sun. We find indications of a connection between flare induced localized seismic signals and the excitation of global high-frequency oscillations in the Sun., Comment: 29 pages, 7 figures, To appear in The Astrophysical Journal

Analysis of a time series of high spatial resolution vector magnetograms of the active region NOAA 10930 available from SOT/SP on-board Hinode revealed that there is a mixture of upward and downward currents in the two foot-points of an emerging flux-rope. The flux emergence rate is almost the same in both the polarities. We observe that along with an increase in magnetic flux, the net current in each polarity increases initially for about three days after which it decreases. This net current is characterized by having exactly opposite signs in each polarities while its magnitude remains almost the same most of the time. The decrease of net current in both the polarities is due to the increase of current having a sign opposite to that of the net current. The dominant current, with same sign as the net current, is seen to increase first and then decreases during the major X-class flares. Evolution of non-dominant current appears to be a necessary condition for a flare initiation. The above observations can have a plausible explanation in terms of the superposition of two different force-free states resulting in non-zero Lorentz force in the corona. This Lorentz force then push the coronal plasma and might facilitate the magnetic reconnection required for flares. Also, the evolution of the net current is found to follow the evolution of magnetic shear at the polarity inversion line., Comment: 24 pages, 6 figures, Submitted to Astrophysical Journal

A magnetic field is force-free if there is no interaction between the magnetic field and plasma in surrounding atmosphere i.e., electric currents are aligned with the magnetic field, giving rise to zero Lorentz force. Computation of various magnetic parameters such as magnetic energy, gradient of twist of sunspot fields and any kind of extrapolations, heavily hinge on the force-free approximation of the photospheric sunspot magnetic fields. Thus it is important to inspect the force-freeness of sunspot fields. The force-freeness of sunspot magnetic fields has been examined earlier by some researchers ending with incoherent results. Accurate photospheric vector field measurements with high spatial resolution are required to inspect the force-free nature of sunspots. We use several such vector magnetograms obtained from the Solar Optical Telescope/Spectro-Polarimeter aboard the Hinode. Both necessary and sufficient conditions for force-freeness are examined by checking global and local nature of magnetic forces over sunspots. We find that the sunspot magnetic fields are not much away from force-free configuration, although they are not completely force-free on the photosphere. The umbral and inner penumbral fields are more force-free than the middle and the outer penumbral fields. During their evolution, sunspot magnetic fields are found to maintain their proximity to force-free behaviour. Although a dependence of net Lorentz force components is seen on the evolutionary stages of the sunspots, we don't find a systematic relationship between the nature of sunspot fields and associated flare activity. Further, we examine whether the fields at photosphere follow linear or non-linear force free conditions. After examining this in various complex and simple sunspots we conclude that,in either case,the photospheric sunspot fields are closer to satisfy non linear force-free field approximation., Comment: 34 pages, 4 figures, 2 tables; accepted for publication in the Astrophysical Journal

Background: Chemotherapy-induced reduction in tumor load is a function of apoptotic cell death, orchestrated by intracellular caspases. However, the effectiveness of these therapies is compromised by mutations affecting specific genes, controlling and/or regulating apoptotic signaling. Therefore, it is desirable to identify novel pathways of cell death, which could function in tandem with or in the absence of efficient apoptotic machinery. In this regard, recent evidence supports the existence of a novel cell death pathway termed autophagy, which is activated upon growth factor deprivation or exposure to genotoxic compounds. The functional relevance of this pathway in terms of its ability to serve as a stress response or a truly death effector mechanism is still in question; however, reports indicate that autophagy is a specialized form of cell death under certain conditions. Methodology/Principal Findings: We report here the simultaneous induction of non-canonical autophagy and apoptosis in human cancer cells upon exposure to a small molecule compound that triggers intracellular hydrogen peroxide (H2O2) production. Whereas, silencing of beclin1 neither inhibited the hallmarks of autophagy nor the induction of cell death, Atg 7 or Ulk1 knockdown significantly abrogated drug-induced H2O2-mediated autophagy. Furthermore, we provide evidence that activated extracellular regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) are upstream effectors controlling both autophagy and apoptosis in response to elevated intracellular H2O2. Interestingly, inhibition of JNK activity reversed the increase in Atg7 expression in this system, thus indicating that JNK may regulate autophagy by activating Atg7. Of note, the small molecule compound triggered autophagy and apoptosis in primary cells derived from patients with lymphoma, but not in non-transformed cells. Conclusions/Significance: Considering that loss of tumor suppressor beclin 1 is associated with neoplasia, the ability, Singapore. Biomedical Research Council, Singapore. Ministry of Education

Magnetic twist of the active region has been measured over a decade using photospheric vector field data, chromospheric H_alpha data, and coronal loop data. The twist and tilt of the active regions have been measured at the photospheric level with the vector magnetic field measurements. The active region NOAA 10930 is a highly twisted emerging region. The same active region produced several flares and has been extensively observed by Hinode. In this paper, we will show the evolution of twist and tilt in this active region leading up to the two X-class flares. We find that the twist initially increases with time for a few days with a simultaneous decrease in the tilt until before the X3.4 class flare on December 13, 2006. The total twist acquired by the active region is larger than one complete winding before the X3.4 class flare and it decreases in later part of observations. The injected helicity into the corona is negative and it is in excess of 10^43 Mx^2 before the flares., Comment: 12 pages, 5 Figures, Accepted in Advances in Geosciences (Solar-Terrestrial Sciences)

Helicity measures complexity in the field. Magnetic helicity is given by a volume integral over the scalar product of magnetic field {\bf B} and its vector potential {\bf A}. A direct computation of magnetic helicity in the solar atmosphere is not possible due to unavailability of the observations at different heights and also due to non-uniqueness of {\bf A}. The force-free parameter $\alpha$ has been used as a proxy of magnetic helicity for a long time. We have clarified the physical meaning of $\alpha$ and its relationship with the magnetic helicity. We have studied the effect of polarimetric noise on estimation of various magnetic parameters. Fine structures of sunspots in terms of vertical current ($J_z$) and $\alpha$ have been examined. We have introduced the concept of signed shear angle (SSA) for sunspots and established its importance for non force-free fields. We find that there is no net current in sunspots even in presence of a significant twist, showing consistency with their fibril-bundle nature. The finding of existence of a lower limit of SASSA for a given class of X-ray flare will be very useful for space weather forecasting. A good correlation is found between the sign of helicity in the sunspots and the chirality of the associated chromospheric and coronal features. We find that a large number of sunspots observed in the declining phase of solar cycle 23 do not follow the hemispheric helicity rule whereas most of the sunspots observed in the beginning of new solar cycle 24 do follow. This indicates a long term behaviour of the hemispheric helicity patterns in the Sun. The above sums up my PhD thesis., Comment: 06 pages; To appear in the "Physics of Sun and star spots", Proceedings of IAU Symposium 273, eds. D.P. Choudhary and K.G. Strassmeier

In a force-free magnetic field, there is no interaction of field and the plasma in the surrounding atmosphere i.e., electric currents are aligned with the magnetic field, giving rise to zero Lorentz force. The computation of many magnetic parameters like magnetic energy, gradient of twist of sunspot magnetic fields (computed from the force-free parameter $\alpha$), including any kind of extrapolations heavily hinge on the force-free approximation of the photospheric magnetic fields. The force-free magnetic behaviour of the photospheric sunspot fields has been examined by \cite{metc95} and \cite{moon02} ending with inconsistent results. \cite{metc95} concluded that the photospheric magnetic fields are far from the force-free nature whereas \cite{moon02} found the that the photospheric magnetic fields are not so far from the force-free nature as conventionally regarded. The accurate photospheric vector field measurements with high resolution are needed to examine the force-free nature of sunspots. We use high resolution vector magnetograms obtained from the Solar Optical Telescope/Spectro-Polarimeter (SOT/SP) aboard Hinode to inspect the force-free behaviour of the photospheric sunspot magnetic fields. Both the necessary and sufficient conditions for force-freeness are examined by checking global as well as as local nature of sunspot magnetic fields. We find that the sunspot magnetic fields are very close to the force-free approximation, although they are not completely force-free on the photosphere., Comment: 04 pages; To appear in the "Physics of Sun and star spots", Proceedings of IAU Symposium 273, eds. D.P. Choudhary and K.G. Strassmeier

The high-resolution pictures of the solar photosphere from space based 50 cm Solar Optical Telescope (SOT) on-board Hinode spacecraft, are now routinely observed. Such images of a delta-sunspot in NOAA 10930 were obtained by Hinode during 13 December 2006 while a X-class flare occurred in this active region. Two bright ribbons were visible even in white light and G-band images apart from chromospheric Ca II H images. We register the sunspot globally using cross-correlation technique and analyse local effects during flare interval. We find that during flare the penumbral filaments show lateral motion. Also, we locate two patches, one in either polarity, which show converging motion towards the polarity inversion line (PIL). In Ca II H images we find kernel with pre-flare brightening which lie along the PIL., Comment: 4 pages (ASP style), 2 figures, for the proceedings of "Hinode-3:The third Hinode Science Meeting" Tokyo

Predicting the severity of the solar eruptive phenomena like flares and Coronal Mass Ejections (CMEs) remains a great challenge despite concerted efforts for several decades. The advent of high quality vector magnetograms obtained from Hinode (SOT/SP) has increased the possibility of meeting this challenge. In particular, the Spatially Averaged Signed Shear Angle (SASSA) seems to be an unique parameter to quantify the non-potentiality of the active regions. We demonstrate the usefulness of SASSA for predicting the flare severity. For this purpose we present case studies of the evolution of magnetic non-potentiality using 115 vector magnetograms of four active regions namely ARs NOAA 10930, 10960, 10961 and 10963 during December 08-15, 2006, June 03-10, 2007, June 28-July 5, 2007 and July 10-17, 2007 respectively. The NOAA ARs 10930 and 10960 were very active and produced X and M class flares respectively, along with many smaller X-ray flares. On the other hand, the NOAA ARs 10961 and 10963 were relatively less active and produced only very small (mostly A and B-class) flares. For this study we have used a large number of high resolution vector magnetograms obtained from Hinode (SOT/SP). The analysis shows that the peak X-ray flux of the most intense solar flare emanating from the active regions depends on the magnitude of the SASSA at the time of the flare. This finding of the existence of a lower limit of SASSA for a given class of X-ray flare will be very useful for space weather forecasting. We have also studied another non-potentiality parameter called mean weighted shear angle (MWSA) of the vector magnetograms along with SASSA. We find that the MWSA does not show such distinction as the SASSA for upper limits of GOES X-Ray flux of solar flares, however both the quantities show similar trends during the evolution of all active regions studied., Comment: 25 pages, 5 figures, accepted for publication in the Astrophysical Journal

The accuracy of Milne-Eddington (ME) inversions, used to retrieve the magnetic field vector, depends upon the signal-to-noise ratio (SNR) of the spectro-polarimetric observations. The SNR in real observations varies from pixel to pixel, therefore the accuracy of the field vector also varies over the map. The aim of this work is to study the effect of polarimetric noise on the inference of magnetic field vector and the magnetic non-potentiality of a real sunspot. To this end, we use Hinode SOT/SP vector magnetogram of a real sunspot NOAA 10933 as an input to generate synthetic Stokes profiles under ME model assumptions. We then add normally-distributed polarimetric noise of the level 0.5\% of continuum intensity to these synthetic profiles and invert them again using ME code. This process is repeated 100 times with different realizations of noise. It is found that within most of the sunspot area (> 90% area) the spread in the (i) field strength is less than 8 Gauss, (ii) field inclination is less than 1 degree, and (iii) field azimuth is less than 5 degrees. Further, we determine the uncertainty in the magnetic non-potentiality of a sunspot as determined by the force-free parameter alpha_g and Spatially Averaged Signed Shear Angle (SASSA). It is found that for the sunspot studied here these parameters are alpha_g = -3.5 +/- 0.37 (x 10^{-9} m^{-1}) and SASSA = -1.68 +/- 0.014 degrees. This suggests that the SASSA is a less dispersion non-potentiality parameter as compared to alpha_g. Further, we examine the effect of increasing noise levels viz. 0.01, 0.1, 0.5 and 1% of continuum intensity and find that SASSA is less vulnerable to noise as compared to alpha_g parameter., Comment: Astrophysical Journal (In Press) 29 pages, 5 figures (scatterplots do not appear in soft-copy but appear on laser-printer)

The equilibrium structure of sunspots depends critically on its magnetic topology and is dominated by magnetic forces. Tension force is one component of the Lorentz force which balances the gradient of magnetic pressure in force-free configurations. We employ the tension term of the Lorentz force to clarify the structure of sunspot features like penumbral filaments, umbral light bridges and outer penumbral fine structures. We compute vertical component of tension term of Lorentz force over two active regions namely NOAA AR 10933 and NOAA AR 10930 observed on 05 January 2007 and 12 December 2006 respectively. The former is a simple while latter is a complex active region with highly sheared polarity inversion line (PIL). The vector magnetograms used are obtained from Hinode(SOT/SP). We find an inhomogeneous distribution of tension with both positive and negative signs in various features of the sunspots. The existence of positive tension at locations of lower field strength and higher inclination is compatible with the uncombed model of the penumbral structure. Positive tension is also seen in umbral light bridges which could be indication of uncombed structure of the light bridge. Likewise, the upward directed tension associated with bipolar regions in the penumbra could be a direct confirmation of the sea serpent model of penumbral structures. Upward directed tension at the PIL of AR 10930 seems to be related to flux emergence. The magnitude of the tension force is greater than the force of gravity in some places, implying a nearly force-free configuration for these sunspot features. From our study, magnetic tension emerges as a useful diagnostic of the local equilibrium of the sunspot fine structures., Comment: 06 pages, 6 figures; Accepted for publication in the Astronomy & Astrophysics as a "Letter to the Editor"

The X-3.4 class flare of 13 December 2006 was observed with a high cadence of 2 minutes at 0.2 arc-sec resolution by HINODE/SOT FG instrument. The flare ribbons could be seen in G-band images also. A careful analysis of these observations after proper registration of images show flare related changes in penumbral filaments of the associated sunspot, for the first time. The observations of sunspot deformation, decay of penumbral area and changes in magnetic flux during large flares have been reported earlier in the literature. In this Letter, we report lateral motion of the penumbral filaments in a sheared region of the delta-sunspot during the X-class flare. Such shifts have not been seen earlier. The lateral motion occurs in two phases, (i) motion before the flare ribbons move across the penumbral filaments and (ii) motion afterwards. The former motion is directed away from expanding flare ribbons and lasts for about four minutes. The latter motion is directed in the opposite direction and lasts for more than forty minutes. Further, we locate a patch in adjacent opposite polarity spot moving in opposite direction to the penumbral filaments. Together these patches represent conjugate foot-points on either side of the polarity inversion line (PIL), moving towards each other. This converging motion could be interpreted as shrinkage of field lines., Comment: 20 pages, 3 figures, Accepted for publication in Astrophysical Journal Letters

Various theoretical and observational results have been reported regarding the presence/absence of net electric currents in the sunspots. The limited spatial resolution of the earlier observations perhaps obscured the conclusions. We have analyzed 12 sunspots observed from Hinode (SOT/SP) to clarify the issue. The azimuthal and radial components of magnetic fields and currents have been derived. The azimuthal component of the magnetic field of sunspots is found to vary in sign with azimuth. The radial component of the field also varies in magnitude with azimuth. While the latter pattern is a confirmation of the interlocking combed structure of penumbral filaments, the former pattern shows that the penumbra is made up of a "curly interlocking combed" magnetic field. The azimuthally averaged azimuthal component is seen to decline much faster than 1/$\varpi$ in the penumbra, after an initial increase in the umbra, for all the spots studied. This confirms the confinement of magnetic fields and absence of a net current for sunspots as postulated by \cite{parker96}. The existence of a global twist for a sunspot even in the absence of a net current is consistent with a fibril-bundle structure of the sunspot magnetic fields., Comment: 15 pages, 4 figures, 1 table; accepted for publication in the ApJ Letters

The presence of fine structures in the sunspot vector magnetic fields has been confirmed from Hinode as well as other earlier observations. We studied 43 sunspots based on the data sets taken from ASP/DLSP, Hinode (SOT/SP) and SVM (USO). In this \emph{Letter}, (i) We introduce the concept of signed shear angle (SSA) for sunspots and establish its importance for non force-free fields. (ii) We find that the sign of global $\alpha$ (force-free parameter) is well correlated with the global SSA and the photospheric chirality of sunspots. (iii) Local $\alpha$ patches of opposite signs are present in the umbra of each sunspot. The amplitude of the spatial variation of local $\alpha$ in the umbra is typically of the order of the global $\alpha$ of the sunspot. (iv) We find that the local $\alpha$ is distributed as alternately positive and negative filaments in the penumbra. The amplitude of azimuthal variation of the local $\alpha$ in the penumbra is approximately an order of magnitude larger than that in the umbra. The contributions of the local positive and negative currents and $\alpha$ in the penumbra cancel each other giving almost no contribution for their global values for whole sunspot. (v) Arc-like structures (partial rings) with a sign opposite to that of the dominant sign of $\alpha$ of the umbral region are seen at the umbral-penumbral boundaries of some sunspots. (vi) Most of the sunspots studied, belong to the minimum epoch of the 23$^{rd}$ solar cycle and do not follow the so-called hemispheric helicity rule., Comment: 15 pages, 3 figures, 1 table; Accepted for publication in the ApJ Letters

We have studied the evolution of magnetic helicity and chirality in an active region over three consecutive solar rotations. The region when it first appeared was named NOAA10923 and in subsequent rotations it was numbered NOAA 10930, 10935 and 10941. We compare the chirality of these regions at photospheric, chromospheric and coronal heights. The observations used for photospheric and chromospheric heights are taken from Solar Vector Magnetograph (SVM) and H_alpha imaging telescope of Udaipur Solar Observatory (USO), respectively. We discuss the chirality of the sunspots and associated H_alpha filaments in these regions. We find that the twistedness of superpenumbral filaments is maintained in the photospheric transverse field vectors also. We also compare the chirality at photospheric and chromospheric heights with the chirality of the associated coronal loops, as observed from the HINODE X-Ray Telescope., Comment: 8 pages, 4 figures

The force-free parameter $\alpha$, also known as helicity parameter or twist parameter, bears the same sign as the magnetic helicity under some restrictive conditions. The single global value of $\alpha$ for a whole active region gives the degree of twist per unit axial length. We investigate the effect of polarimetric noise on the calculation of global $\alpha$ value and magnetic energy of an analytical bipole. The analytical bipole has been generated using the force-free field approximation with a known value of constant $\alpha$ and magnetic energy. The magnetic parameters obtained from the analytical bipole are used to generate Stokes profiles from the Unno-Rachkovsky solutions for polarized radiative transfer equations. Then we add random noise of the order of 10$^{-3}$ of the continuum intensity (I$_{c}$) in these profiles to simulate the real profiles obtained by modern spectropolarimeters like Hinode (SOT/SP), SVM (USO), ASP, DLSP, POLIS, SOLIS etc. These noisy profiles are then inverted using a Milne-Eddington inversion code to retrieve the magnetic parameters. Hundred realizations of this process of adding random noise and polarimetric inversion is repeated to study the distribution of error in global $\alpha$ and magnetic energy values. The results show that : (1). the sign of $\alpha$ is not influenced by polarimetric noise and very accurate values of global twist can be calculated, and (2). accurate estimation of magnetic energy with uncertainty as low as 0.5% is possible under the force-free condition., Comment: 33 pages, 6 figures, 1 table; Accepted for publication in the ApJ