Association between the c.*229C>T polymorphism of the topoisomerase IIb binding protein 1 (TopBP1) gene and breast cancer

Topoisomerase IIb binding protein 1 (TopBP1) is involved in cell survival, DNA replication, DNA damage repair and cell cycle checkpoint control. The biological function of TopBP1 and its close relation with BRCA1 prompted us to investigate whether alterations in the TopBP1 gene can influence the risk of breast cancer. The aim of this study was to examine the association between five polymorphisms (rs185903567, rs116645643, rs115160714, rs116195487, and rs112843513) located in the 30UTR region of the TopBP1 gene and breast cancer risk as well as allele-specific gene expression. Five hundred thirty-four breast cancer patients and 556 population controls were genotyped for these SNPs. Allele-specific Top- BP1 mRNA and protein expressions were determined by using real time PCR and western blotting methods, respectively. Only one SNP (rs115160714) showed an association with breast cancer. Compared to homozygous common allele carriers, heterozygous and homozygous for the T variant had significantly increased risk of breast cancer (adjusted odds ratio = 3.81, 95 % confidence interval: 1.63–8.34, p = 0.001). Mean TopBP1 mRNA and protein expression were higher in the individuals with the CT or TT genotype. There was a significant association between the rs115160714 and tumor grade and stage. Most carriers of minor allele had a high grade (G3) tumors classified as T2-T4N1M0. Our study raises a possibility that a genetic variation of TopBP1 may be implicated in the etiology of breast cancer

Coupled coarse graining and Markov Chain Monte Carlo for lattice systems

We propose an efficient Markov Chain Monte Carlo method for sampling equilibrium distributions for stochastic lattice models, capable of handling correctly long and short-range particle interactions. The proposed method is a Metropolis-type algorithm with the proposal probability transition matrix based on the coarse-grained approximating measures introduced in a series of works of M. Katsoulakis, A. Majda, D. Vlachos and P. Plechac, L. Rey-Bellet and D.Tsagkarogiannis,. We prove that the proposed algorithm reduces the computational cost due to energy differences and has comparable mixing properties with the classical microscopic Metropolis algorithm, controlled by the level of coarsening and reconstruction procedure. The properties and effectiveness of the algorithm are demonstrated with an exactly solvable example of a one dimensional Ising-type model, comparing efficiency of the single spin-flip Metropolis dynamics and the proposed coupled Metropolis algorithm.Comment: 20 pages, 4 figure

Magnetars and pulsars: a missing link

There is growing evidence that soft gamma-ray repeaters (SGRs) and anomalous X-ray pulsars (AXPs) are isolated neutron stars with superstrong magnetic fields, i.e., magnetars, marking them a distinguished species from the conventional species of spindown-powered isolated neutron stars, i.e., radio pulsars. The current arguments in favor of the magnetar interpretation of SGR/AXP phenomenology will be outlined, and the two energy sources in magnetars, i.e. a magnetic dissipation energy and a spindown energy, will be reviewed. I will then discuss a missing link between magnetars and pulsars, i.e., lack of the observational evidence of the spindown-powered behaviors in known magnetars. Some recent theoretical efforts in studying such behaviors will be reviewed along with some predictions testable in the near future.Comment: Invited talk at the Sixth Pacific Rim Conference on Stellar Astrophysics, a tribute to Helmut A. Abt, July 11-17, 2002, Xi'an. To appear in the proceedings (eds. K. S. Cheng, K. C. Leung & T. P. Li

Evolution of cooperation driven by zealots

Recent experimental results with humans involved in social dilemma games suggest that cooperation may be a contagious phenomenon and that the selection pressure operating on evolutionary dynamics (i.e., mimicry) is relatively weak. I propose an evolutionary dynamics model that links these experimental findings and evolution of cooperation. By assuming a small fraction of (imperfect) zealous cooperators, I show that a large fraction of cooperation emerges in evolutionary dynamics of social dilemma games. Even if defection is more lucrative than cooperation for most individuals, they often mimic cooperation of fellows unless the selection pressure is very strong. Then, zealous cooperators can transform the population to be even fully cooperative under standard evolutionary dynamics.Comment: 5 figure

Nanostructured 3D Constructs Based on Chitosan and Chondroitin Sulphate Multilayers for Cartilage Tissue Engineering

Nanostructured three-dimensional constructs combining layer-by-layer technology (LbL) and template leaching were processed and evaluated as possible support structures for cartilage tissue engineering. Multilayered constructs were formed by depositing the polyelectrolytes chitosan (CHT) and chondroitin sulphate (CS) on either bidimensional glass surfaces or 3D packet of paraffin spheres. 2D CHT/CS multi-layered constructs proved to support the attachment and proliferation of bovine chondrocytes (BCH). The technology was transposed to 3D level and CHT/CS multi-layered hierarchical scaffolds were retrieved after paraffin leaching. The obtained nanostructured 3D constructs had a high porosity and water uptake capacity of about 300%. Dynamical mechanical analysis (DMA) showed the viscoelastic nature of the scaffolds. Cellular tests were performed with the culture of BCH and multipotent bone marrow derived stromal cells (hMSCs) up to 21 days in chondrogenic differentiation media. Together with scanning electronic microscopy analysis, viability tests and DNA quantification, our results clearly showed that cells attached, proliferated and were metabolically active over the entire scaffold. Cartilaginous extracellular matrix (ECM) formation was further assessed and results showed that GAG secretion occurred indicating the maintenance of the chondrogenic phenotype and the chondrogenic differentiation of hMSCs

Time-resolved measurements of fast electron recirculation for relativistically intense femtosecond scale laser-plasma interactions

A key issue in realising the development of a number of applications of high-intensity lasers is the dynamics of the fast electrons produced and how to diagnose them. We report on measurements of fast electron transport in aluminium targets in the ultra-intense, short-pulse (<50 fs) regime using a high resolution temporally and spatially resolved optical probe. The measurements show a rapidly (≈0.5c) expanding region of Ohmic heating at the rear of the target, driven by lateral transport of the fast electron population inside the target. Simulations demonstrate that a broad angular distribution of fast electrons on the order of 60° is required, in conjunction with extensive recirculation of the electron population, in order to drive such lateral transport. These results provide fundamental new insight into fast electron dynamics driven by ultra-short laser pulses, which is an important regime for the development of laser-based radiation and particle sources

Synergistic Antibacterial Effects of Metallic Nanoparticle Combinations

© The Author(s) 2019.Metallic nanoparticles have unique antimicrobial properties that make them suitable for use within medical and pharmaceutical devices to prevent the spread of infection in healthcare. The use of nanoparticles in healthcare is on the increase with silver being used in many devices. However, not all metallic nanoparticles can target and kill all disease-causing bacteria. To overcome this, a combination of several different metallic nanoparticles were used in this study to compare effects of multiple metallic nanoparticles when in combination than when used singly, as single elemental nanoparticles (SENPs), against two common hospital acquired pathogens (Staphylococcus aureus and Pseudomonas. aeruginosa). Flow cytometry LIVE/DEAD assay was used to determine rates of cell death within a bacterial population when exposed to the nanoparticles. Results were analysed using linear models to compare effectiveness of three different metallic nanoparticles, tungsten carbide (WC), silver (Ag) and copper (Cu), in combination and separately. Results show that when the nanoparticles are placed in combination (NPCs), antimicrobial effects significantly increase than when compared with SENPs (P < 0.01). This study demonstrates that certain metallic nanoparticles can be used in combination to improve the antimicrobial efficiency in destroying morphologically distinct pathogens within the healthcare and pharmaceutical industry.Peer reviewe

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Climate change has likely already affected global food production

Crop yields are projected to decrease under future climate conditions, and recent research suggests that yields have already been impacted. However, current impacts on a diversity of crops subnationally and implications for food security remains unclear. Here, we constructed linear regression relationships using weather and reported crop data to assess the potential impact of observed climate change on the yields of the top ten global crops–barley, cassava, maize, oil palm, rapeseed, rice, sorghum, soybean, sugarcane and wheat at ~20,000 political units. We find that the impact of global climate change on yields of different crops from climate trends ranged from -13.4% (oil palm) to 3.5% (soybean). Our results show that impacts are mostly negative in Europe, Southern Africa and Australia but generally positive in Latin America. Impacts in Asia and Northern and Central America are mixed. This has likely led to ~1% average reduction (-3.5 X 1013 kcal/year) in consumable food calories in these ten crops. In nearly half of food insecure countries, estimated caloric availability decreased. Our results suggest that climate change has already affected global food production