Valosin-containing protein regulates the proteasome-mediated degradation of DNA-PKcs in glioma cells.

DNA-dependent protein kinase (DNA-PK) has an important role in the repair of DNA damage and regulates the radiation sensitivity of glioblastoma cells. The VCP (valosine-containing protein), a chaperone protein that regulates ubiquitin-dependent protein degradation, is phosphorylated by DNA-PK and recruited to DNA double-strand break sites to regulate DNA damage repair. However, it is not clear whether VCP is involved in DNA-PKcs (DNA-PK catalytic subunit) degradation or whether it regulates the radiosensitivity of glioblastoma. Our data demonstrated that DNA-PKcs was ubiquitinated and bound to VCP. VCP knockdown resulted in the accumulation of the DNA-PKcs protein in glioblastoma cells, and the proteasome inhibitor MG132 synergised this increase. As expected, this increase promoted the efficiency of DNA repair in several glioblastoma cell lines; in turn, this enhanced activity decreased the radiation sensitivity and prolonged the survival fraction of glioblastoma cells in vitro. Moreover, the VCP knockdown in glioblastoma cells reduced the survival time of the xenografted mice with radiation treatment relative to the control xenografted glioblastoma mice. In addition, the VCP protein was also downregulated in ~25% of GBM tissues from patients (WHO, grade IV astrocytoma), and the VCP protein level was correlated with patient survival (R(2)=0.5222, P<0.05). These findings demonstrated that VCP regulates DNA-PKcs degradation and increases the sensitivity of GBM cells to radiation

Classification on imbalanced data sets, taking advantage of errors to improve performance

Classification methods usually exhibit a poor performance when they are applied on imbalanced data sets. In order to overcome this problem, some algorithms have been proposed in the last decade. Most of them generate synthetic instances in order to balance data sets, regardless the classification algorithm. These methods work reasonably well in most cases; however, they tend to cause over-fitting. In this paper, we propose a method to face the imbalance problem. Our approach, which is very simple to implement, works in two phases; the first one detects instances that are difficult to predict correctly for classification methods. These instances are then categorized into “noisy” and “secure”, where the former refers to those instances whose most of their nearest neighbors belong to the opposite class. The second phase of our method, consists in generating a number of synthetic instances for each one of those that are difficult to predict correctly. After applying our method to data sets, the AUC area of classifiers is improved dramatically. We compare our method with others of the state-of-the-art, using more than 10 data sets

Intermediate-statistics spin waves

In this paper, we show that spin waves, the elementary excitation of the Heisenberg magnetic system, obey a kind of intermediate statistics with a finite maximum occupation number n. We construct an operator realization for the intermediate statistics obeyed by magnons, the quantized spin waves, and then construct a corresponding intermediate-statistics realization for the angular momentum algebra in terms of the creation and annihilation operators of the magnons. In other words, instead of the Holstein-Primakoff representation, a bosonic representation subject to a constraint on the occupation number, we present an intermediate-statistics representation with no constraints. In this realization, the maximum occupation number is naturally embodied in the commutation relation of creation and annihilation operators, while the Holstein-Primakoff representation is a bosonic operator relation with an additional putting-in-by-hand restriction on the occupation number. We deduce the intermediate-statistics distribution function for magnons. On the basis of these results, we calculate the dispersion relations for ferromagnetic and antiferromagnetic spin waves. The relations between the intermediate statistics that magnons obey and the other two important kinds of intermediate statistics, Haldane-Wu statistics and the fractional statistics of anyons, are discussed. We also compare the spectrum of the intermediate-statistics spin wave with the exact solution of the one-dimensional s = 1/2 Heisenberg model, which is obtained by the Bethe ansatz method. For ferromagnets, we take the contributions from the interaction between magnons (the quartic contribution), the next-to-nearest neighbor interaction, and the dipolar interaction into account for comparison with the experiment.Comment: 22 pages, 2 figure

Investigation of dietary fiber, protein, vitamin E and other nutritional compounds of banana flower of two cultivars grown in China

The nutritional composition of banana flowers of two cultivars [cvs. Baxijiao (AAA) and Paradisical (AAB)] grown in Hainan of China has been studied. Flower samples were collected and extracted according to methods of Association of Official Analytical Chemists (AOAC). Results showed thatbanana flowers contained abundant dietary fiber (4.96-5.74 g/100g) and proteins (1.62-2.07 g/100 g). The major amino acids are glycine, leucine, alanine, and aspartic acid. Lysine had a lowest chemical score of 64% among the essential amino acids. In both species, flowers contained a higher composition of unsaturated fatty acids (65-66%), mainly the linoleic acid, while saturated fatty acids (mainly palmitic acid) is low. The contents of vitamin E, total saponin and flavonoids were 0.87-1.07, 0.12 and 5.27–5.90mg/100 g, respectively. This study provides a fundamental nutritional data of banana flowers which can be essential in food science

Continuous quantum measurement of two coupled quantum dots using a point contact: A quantum trajectory approach

We obtain the finite-temperature unconditional master equation of the density matrix for two coupled quantum dots (CQD) when one dot is subjected to a measurement of its electron occupation number using a point contact (PC). To determine how the CQD system state depends on the actual current through the PC device, we use the so-called quantum trajectory method to derive the zero-temperature conditional master equation. We first treat the electron tunneling through the PC barrier as a classical stochastic point process (a quantum-jump model). Then we show explicitly that our results can be extended to the quantum-diffusive limit when the average electron tunneling rate is very large compared to the extra change of the tunneling rate due to the presence of the electron in the dot closer to the PC. We find that in both quantum-jump and quantum-diffusive cases, the conditional dynamics of the CQD system can be described by the stochastic Schr\"{o}dinger equations for its conditioned state vector if and only if the information carried away from the CQD system by the PC reservoirs can be recovered by the perfect detection of the measurements.Comment: 14 pages, 1 figures, RevTex, onecolumn, to appear in Phys. Rev.

Thermal Hydraulics Phenomena Identification and Ranking Table (PIRT) for Advanced High Temperature Reactor (AHTR)

U.S. Department of Energy (DOE) Office of Nuclear Energy's Nuclear Energy University Programshttps://deepblue.lib.umich.edu/bitstream/2027.42/138121/1/Thermal hydraulic PIRT for AHTR.pd

Non-abelian Action for Multiple Five-Branes with Self-Dual Tensors

We construct an action for non-abelian 2-form in 6-dimensions. Our action consists of a non-abelian generalization of the abelian action of Perry and Schwarz for a single five-brane. It admits a self-duality equation on the field strength as the equation of motion. It has a modified 6d Lorentz symmetry. On dimensional reduction on a circle, our action gives the standard 5d Yang-Mills action plus higher order corrections. Based on these properties, we propose that our theory describes the gauge sector of multiple M5-branes in flat space.Comment: LaTeX, 26 pages. v2: improved discussion of Lorentz symmetry. ref added. v3: add comments in the discussion section on the inclusion of scalar fields and supersymmetry; title changed to a more suitable one; version published in JHE

Combating antimicrobial resistance: the silent war

Once hailed as miraculous solutions, antibiotics no longer hold that status. The excessive use of antibiotics across human healthcare, agriculture, and animal husbandry has given rise to a broad array of multidrug-resistant (MDR) pathogens, posing formidable treatment challenges. Antimicrobial resistance (AMR) has evolved into a pressing global health crisis, linked to elevated mortality rates in the modern medical era. Additionally, the absence of effective antibiotics introduces substantial risks to medical and surgical procedures. The dwindling interest of pharmaceutical industries in developing new antibiotics against MDR pathogens has aggravated the scarcity issue, resulting in an exceedingly limited pipeline of new antibiotics. Given these circumstances, the imperative to devise novel strategies to combat perilous MDR pathogens has become paramount. Contemporary research has unveiled several promising avenues for addressing this challenge. The article provides a comprehensive overview of these innovative therapeutic approaches, highlighting their mechanisms of action, benefits, and drawbacks

Characterization of heterogeneity and spatial distribution of phases in complex solid dispersions by thermal analysis by structural characterization and X-ray micro computed tomography

Purpose: This study investigated the effect of drug-excipient miscibility on the heterogeneity and spatial distribution of phase separation in pharmaceutical solid dispersions at a micron-scale using two novel and complementary characterization techniques, thermal analysis by structural characterization (TASC) and X-ray micro-computed tomography (XCT) in conjunction with conventional characterization methods. Method: Complex dispersions containing felodipine, TPGS, PEG and PEO were prepared using hot melt extrusion-injection moulding. The phase separation behavior of the samples was characterized using TASC and XCT in conjunction with conventional thermal, microscopic and spectroscopic techniques. The in vitro drug release study was performed to demonstrate the impact of phase separation on dissolution of the dispersions. Results: The conventional characterization results indicated the phase separating nature of the carrier materials in the patches and the presence of crystalline drug in the patches with the highest drug loading (30% w/w). TASC and XCT where used to provide insight into the spatial configuration of the separate phases. TASC enabled assessment of the increased heterogeneity of the dispersions with increasing the drug loading. XCT allowed the visualization of the accumulation of phase separated (crystalline) drug clusters at the interface of air pockets in the patches with highest drug loading which led to poor dissolution performance. Semi-quantitative assessment of the phase separated drug clusters in the patches were attempted using XCT. Conclusion: TASC and XμCT can provide unique information regarding the phase separation behavior of solid dispersions which can be closely associated with important product quality indicators such as heterogeneity and microstructure