35 research outputs found

    The neutron production rate measurement of an indigenously developed compact D-D neutron generator

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    One electrostatic accelerator based compact neutron generator was developed. The deuterium ions generated by the ion source were accelerated by one accelerating gap after the extraction from the ion source and bombarded to a target. Two different types of targets, the drive - in titanium target and the deuteriated titanium target were used. The neutron generator was operated at the ion source discharge potential at +Ve 1 kV that generates the deuterium ion current of 200 mA at the target while accelerated through a negative potential of 80 kV in the vacuum at 1.3×10-2 Pa filled with deuterium gas. A comparative study for the neutron yield with both the targets was carried out. The neutron flux measurement was done by the bubble detectors purchased from Bubble Technology Industries. The number of bubbles formed in the detector is the direct measurement of the total energy deposited in the detector. By counting the number of bubbles the total dose was estimated. With the help of the ICRP-74 neutron flux to dose equivalent rate conversion factors and the solid angle covered by the detector, the total neutron flux was calculated. In this presentation the operation of the generator, neutron detection by bubble detector and estimation of neutron flux has been discussed

    Fibronectin on the Surface of Myeloma Cell-derived Exosomes Mediates Exosome-Cell Interactions

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    Exosomes regulate cell behavior by binding to and delivering their cargo to target cells; however, the mechanisms mediating exosome-cell interactions are poorly understood. Heparan sulfates on target cell surfaces can act as receptors for exosome uptake, but the ligand for heparan sulfate on exosomes has not been identified. Using exosomes isolated from myeloma cell lines and from myeloma patients, we identify exosomal fibronectin as a key heparan sulfate-binding ligand and mediator of exosome-cell interactions. We discovered that heparan sulfate plays a dual role in exosome-cell interaction; heparan sulfate on exosomes captures fibronectin, and on target cells it acts as a receptor for fibronectin. Removal of heparan sulfate from the exosome surface releases fibronectin and dramatically inhibits exosome-target cell interaction. Antibody specific for the Hep-II heparin-binding domain of fibronectin blocks exosome interaction with tumor cells or with marrow stromal cells. Regarding exosome function, fibronectin-mediated binding of exosomes to myeloma cells activated p38 and pERK signaling and expression of downstream target genes DKK1 and MMP-9, two molecules that promote myeloma progression. Antibody against fibronectin inhibited the ability of myeloma-derived exosomes to stimulate endothelial cell invasion. Heparin or heparin mimetics including Roneparstat, a modified heparin in phase I trials in myeloma patients, significantly inhibited exosome-cell interactions. These studies provide the first evidence that fibronectin binding to heparan sulfate mediates exosome-cell interactions, revealing a fundamental mechanism important for exosome-mediated cross-talk within tumor microenvironments. Moreover, these results imply that therapeutic disruption of fibronectin-heparan sulfate interactions will negatively impact myeloma tumor growth and progression

    Poziotinib Inhibits HER2-Mutant-Driven Therapeutic Resistance and Multiorgan Metastasis in Breast Cancer

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    UNLABELLED: The pan-HER tyrosine kinase inhibitor (TKI) neratinib is therapeutically active against metastatic breast cancers harboring activating HER2 mutations, but responses are variable and often not durable. Here we demonstrate that recurrent HER2 mutations have differential effects on endocrine therapy responsiveness, metastasis, and pan-HER TKI therapeutic sensitivity. The prevalence and prognostic significance may also depend on whether the HER2 mutant has arisen in the context of lobular versus ductal histology. The most highly recurrent HER2 mutant, L755S, was particularly resistant to neratinib but sensitive to the pan-HER TKI poziotinib, alone or in combination with fulvestrant. Poziotinib reduced tumor growth, diminished multiorgan metastasis, and inhibited mTOR activation more effectively than neratinib. Similar therapeutic effects of poziotinib were observed in both an engineered HER2L755S MCF7 model and a patient-derived xenograft harboring a HER2G778_P780dup mutation. Overall, these findings support the need for clinical evaluation of poziotinib for the treatment of HER2-mutant metastatic breast cancer. SIGNIFICANCE: Evaluation of the functional impact of HER2 mutations on therapy-induced resistance and metastasis identifies robust antitumor activity of poziotinib and supports the clinical evaluation of poziotinib in ER+ HER2 mutant breast cancer

    Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

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    A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic

    Detection of fast burst of neutrons in the background of intense electromagnetic pulse

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    449-454<span style="font-size:14.0pt;line-height: 115%;font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:black;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">There are many experiments, in which fast neutron burst is emitted along with strong electromagnetic pulse. This pulse has frequency spectrum starting from few tens of kHz to hard X-rays. Detecting these neutrons bursts require special measurement techniques, which are described.</span

    Production of hot spots in low pressure electrical discharges

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    728-733Hot spots (temperature ~ a few keV) have been observed in relatively low density, low temperature (~1 eV) plasma produced by various techniques. The properties of the plasmas were not conducive to radiation collapse, pinching or electron acceleration. Therefore these hot spots were probably produced by thermal run-away process

    Off-centre X-ray emitting regions in X-pinch driven by low energy capacitor bank

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    676-679<span style="font-size:14.0pt;line-height: 115%;font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:black;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">In our X-pinch experiments, driven by a 3.2 kJ bank, it has been observed that X-rays are also emitted from the regions away from the point of contact. They are along the segment of the wires towards the anode. These off-centre X-ray emitting regions can be due to self-reorganization phenomena.</span
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