34 research outputs found
The neutron production rate measurement of an indigenously developed compact D-D neutron generator
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
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
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
Detection of fast burst of neutrons in the background of intense electromagnetic pulse
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
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
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