We investigated r-process nucleosynthesis in magneto-rotational supernovae, based on a new explosion mechanism induced by the magneto-rotational instability (MRI). A series of axisymmetric ...magneto-hydrodynamical simulations with detailed microphysics including neutrino heating is performed, numerically resolving the MRI. Neutrino-heating dominated explosions, enhanced by magnetic fields, showed mildly neutron-rich ejecta producing nuclei up to (i.e., the weak r-process), while explosion models with stronger magnetic fields reproduce a solar-like r-process pattern. More commonly seen abundance patterns in our models are in between the weak and regular r-process, producing lighter and intermediate-mass nuclei. These intermediate r-processes exhibit a variety of abundance distributions, compatible with several abundance patterns in r-process-enhanced metal-poor stars. The amount of Eu ejecta in magnetically driven jets agrees with predicted values in the chemical evolution of early galaxies. In contrast, neutrino-heating dominated explosions have a significant amount of Fe ( ) and Zn, comparable to regular supernovae and hypernovae, respectively. These results indicate magneto-rotational supernovae can produce a wide range of heavy nuclei from iron-group to r-process elements, depending on the explosion dynamics.
We develop a numerical code to calculate the neutrino transfer with multi-energy and multi-angle in three dimensions (3D) for the study of core-collapse supernovae. The numerical code solves the ...Boltzmann equations for neutrino distributions by the discrete-ordinate (S sub(n)) method with a fully implicit differencing for time advance. The Boltzmann equations are formulated in the inertial frame with collision terms being evaluated to the zeroth order of v/c. A basic set of neutrino reactions for three neutrino species is implemented together with a realistic equation of state of dense matter. The pair process is included approximately in order to keep the system linear. We present numerical results for a set of test problems to demonstrate the ability of the code. The numerical treatments of advection and collision terms are validated first in the diffusion and free-streaming limits. Then we compute steady neutrino distributions for a background extracted from a spherically symmetric, general relativistic simulation of a 15 M sub(middot in circle) star and compare them with the results in the latter computation. We also demonstrate multi-dimensional capabilities of the 3D code solving neutrino transfers for artificially deformed supernova cores in 2D and 3D. Formal solutions along neutrino paths are utilized as exact solutions. We plan to apply this code to the 3D neutrino-radiation hydrodynamics simulations of supernovae. This is the first article in a series of reports on the development.
Drug resistance impedes the successful treatment of many types of cancers, especially ovarian cancer (OCa). To counter this problem, we developed novel long-circulating, self-assembled core–shell ...nanoscale coordination polymer (NCP) nanoparticles that efficiently deliver multiple therapeutics with different mechanisms of action to enhance synergistic therapeutic effects. These NCP particles contain high payloads of chemotherapeutics cisplatin or cisplatin plus gemcitabine in the core and pooled siRNAs that target multidrug resistant (MDR) genes in the shell. The NCP particles possess efficient endosomal escape via a novel carbon dioxide release mechanism without compromising the neutral surface charge required for long blood circulation and effectively downregulate MDR gene expression in vivo to enhance chemotherapeutic efficacy by several orders of magnitude. Even at low doses, intraperitoneal injections of nanoparticles led to effective and long-lasting tumor regression/eradication in subcutaneous and intraperitoneal xenograft mouse models of cisplatin-resistant OCa. By silencing MDR genes in tumors, self-assembled core–shell nanoparticles promise a more effective chemotherapeutic treatment for many challenging cancers.
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IJS, KILJ, NUK, PNG, UL, UM
Intra-abdominal tumors, such as ovarian cancer, have a clear predilection for metastasis to the omentum, an organ primarily composed of adipocytes. Currently, it is unclear why tumor cells ...preferentially home to and proliferate in the omentum, yet omental metastases typically represent the largest tumor in the abdominal cavities of women with ovarian cancer. We show here that primary human omental adipocytes promote homing, migration and invasion of ovarian cancer cells, and that adipokines including interleukin-8 (IL-8) mediate these activities. Adipocyte-ovarian cancer cell coculture led to the direct transfer of lipids from adipocytes to ovarian cancer cells and promoted in vitro and in vivo tumor growth. Furthermore, coculture induced lipolysis in adipocytes and β-oxidation in cancer cells, suggesting adipocytes act as an energy source for the cancer cells. A protein array identified upregulation of fatty acid-binding protein 4 (FABP4, also known as aP2) in omental metastases as compared to primary ovarian tumors, and FABP4 expression was detected in ovarian cancer cells at the adipocyte-tumor cell interface. FABP4 deficiency substantially impaired metastatic tumor growth in mice, indicating that FABP4 has a key role in ovarian cancer metastasis. These data indicate adipocytes provide fatty acids for rapid tumor growth, identifying lipid metabolism and transport as new targets for the treatment of cancers where adipocytes are a major component of the microenvironment.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
High-grade serous carcinoma has a poor prognosis, owing primarily to its early dissemination throughout the abdominal cavity. Genomic and proteomic approaches have provided snapshots of the ...proteogenomics of ovarian cancer
, but a systematic examination of both the tumour and stromal compartments is critical in understanding ovarian cancer metastasis. Here we develop a label-free proteomic workflow to analyse as few as 5,000 formalin-fixed, paraffin-embedded cells microdissected from each compartment. The tumour proteome was stable during progression from in situ lesions to metastatic disease; however, the metastasis-associated stroma was characterized by a highly conserved proteomic signature, prominently including the methyltransferase nicotinamide N-methyltransferase (NNMT) and several of the proteins that it regulates. Stromal NNMT expression was necessary and sufficient for functional aspects of the cancer-associated fibroblast (CAF) phenotype, including the expression of CAF markers and the secretion of cytokines and oncogenic extracellular matrix. Stromal NNMT expression supported ovarian cancer migration, proliferation and in vivo growth and metastasis. Expression of NNMT in CAFs led to depletion of S-adenosyl methionine and reduction in histone methylation associated with widespread gene expression changes in the tumour stroma. This work supports the use of ultra-low-input proteomics to identify candidate drivers of disease phenotypes. NNMT is a central, metabolic regulator of CAF differentiation and cancer progression in the stroma that may be therapeutically targeted.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We have discovered room-temperature low-field colossal magnetoresistance (CMR) in an A-site ordered NdBaMn2O6 crystal. The resistance changes more than 2 orders of magnitude at a magnetic field lower ...than 2 T near 300 K. When the temperature and magnetic field sweep from an insulating (metallic) phase to a metallic (insulating) phase, the insulating (metallic) conduction changes to the metallic (insulating) conduction within 1 K and 0.5 T, respectively. The CMR is ascribed to the melting of the charge and orbital ordering. The entropy change which is estimated from the B−T phase diagram is smaller than what is expected for the charge and orbital ordering. The suppression of the entropy change is attributable to the loss of the short-range ferromagnetic fluctuation of Mn spin moments, which is an important key of the high temperature and low magnetic field CMR effect.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
Despite the remarkable progress of 3D graphics technology, the Evans index has been the most popular index for ventricular enlargement. We investigated a novel reliable index for the MR imaging ...features specified in idiopathic normal pressure hydrocephalus, rather than the Evans index.
The patients with suspected idiopathic normal pressure hydrocephalus on the basis of the ventriculomegaly and a triad of symptoms underwent the CSF tap test. CSF volumes were extracted from a T2-weighted 3D spin-echo sequence named "sampling perfection with application-optimized contrasts by using different flip angle evolutions (SPACE)" on 3T MR imaging and were quantified semiautomatically. Subarachnoid spaces were divided as follows: upper and lower parts and 4 compartments of frontal convexity, parietal convexity, Sylvian fissure and basal cistern, and posterior fossa. The maximum length of 3 axial directions in the bilateral ventricles and their frontal horns was measured. The "z-Evans Index" was defined as the maximum z-axial length of the frontal horns to the maximum cranial z-axial length. These parameters were evaluated for the predictive accuracy for the tap-positive groups compared with the tap-negative groups and age-adjusted odds ratios at the optimal thresholds.
In this study, 24 patients with tap-positive idiopathic normal pressure hydrocephalus, 25 patients without response to the tap test, and 23 age-matched controls were included. The frontal horns of the bilateral ventricles were expanded, with the most excessive expansion being toward the z-direction. The CSF volume of the parietal convexity had the highest area under the receiver operating characteristic curve (0.768), the z-Evans Index was the second (0.758), and the upper-to-lower subarachnoid space ratio index was the third (0.723), to discriminate the tap-test response.
The CSF volume of the parietal convexity of <38 mL, upper-to-lower subarachnoid space ratio of <0.33, and the z-Evans Index of >0.42 were newly proposed useful indices for the idiopathic normal pressure hydrocephalus diagnosis, an alternative to the Evans Index.
OBJECTIVE:To estimate whether metformin use by ovarian cancer patients with type II diabetes was associated with improved survival.
METHODS:We reviewed the effect of diabetes and diabetes medications ...on ovarian cancer treatment and outcomes in a single-institution retrospective cohort. Inclusion criteria were International Federation of Gynecology and Obstetrics stage I–IV epithelial ovarian, fallopian, or peritoneal cancer. Exclusion criteria were noninvasive pathology or nonepithelial malignancies. The primary exposures analyzed were history of type II diabetes and diabetes medications. The primary outcomes were progression-free and overall ovarian cancer survival.
RESULTS:Of the 341 ovarian cancer patients included in the study, 297 did not have diabetes, 28 were type II diabetic patients who did not use metformin, and 16 were type II diabetic patients who used metformin. The progression-free survival at 5 years was 51% for diabetic patients who used metformin compared with 23% for the nondiabetic patients and 8% for the diabetic patients who did not use metformin (P=.03). The overall survival at 5 years was 63%, 37%, and 23% for the diabetic patients who used metformin, the nondiabetic patients, and the diabetic patients who did not use metformin, respectively (P=.03). The patients with diabetes received the same treatment for ovarian cancer as the patients without diabetes. The association of metformin use and increased progression-free survival, but not overall survival, remained significant after controlling for standard clinicopathologic parameters.
CONCLUSION:In this ovarian cancer cohort, the patients with type II diabetes who used metformin had longer progression-free survival, despite receiving similar treatment for ovarian cancer.
LEVEL OF EVIDENCE:II
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