17-AAG mediates targeting of HSP90 limits tert activity in peritoneal sarcoma related malignant ascites by downregulating cyclin D1 during cell cycle entry

Aim: Peritoneal or retro-peritoneal sarcomatosis related malignant ascites formation is a rare but serious consequence of the locoregional metastatic event. The present work aimed to study the effect of the Hsp90 inhibitor (17-AAG), an ansamycin analog, on cell cycle and DNA replication specific chaperone-clients interaction in the event of peritoneal sarcoma related malignant ascites formation in mouse model at the late stage of malignant growth. Methods: We administered 17-AAG, an Hsp90 inhibitor, divided doses (330 μg/kg b.w./day for first five days then next ten days with166 μg/kg b.w./day) through intra-peritoneal route of inbred Swiss albino mice bearing full grown peritoneal malignant ascites of sarcoma-180. Our study was evaluated by peripheral blood hemogram analysis, malignant ascitic cytology, cell viability test, survival time and mitotic indexing. Furthermore, flowcytometric HSP90, TERT, CyclinD1, PCNA and GM-CSF expression analysis has been considered for special objective of the study. Results: Our experimental efforts reduced the aggressive proliferation of malignant ascites by drastic downregulation of TERT and cyclin D1 on the verge of cell cycle entry along with DNA replication processivity factor PCNA by directly modulating their folding machinery — heat shock protein 90. Consequently, we observed that malignant ascitic cells became error prone during the event of karyokinesis and produced micronucleus containing malignant cells with low viability. Peripheral neutrophilia due to over-expression of GM-CSF by the peritoneal malignant ascites were also controlled by the treatment with 17-AAG and overall, the treatment modality improved the median survival time. Conclusion: Finally we can conclude that 17AAG administration might serve as a prospective pharmacological agent for the management of peritoneal sarcoma related malignant ascites and throws light towards prolonged survival of the patients concerned

Day of Archaeology 2011–2017: Global Community, Public Engagement, and Digital Practice.

The Day of Archaeology (http://www.dayofarchaeology.com) was a volunteer-led international archaeological blogging event that ran from 2011 to 2017. The project asked people who define themselves as archaeologists to submit one or more blog posts about their working day on a chosen day in June or July. This article explores the history of the Day of Archaeology project and the practicalities of running a large-scale collaborative blogging project, before examining some of the topics covered in the posts. An assessment of the impact of the project follows. Overall, we hope in this work to answer some of the basic questions regarding this type of collaborative, online, global engagement – what we did, who we reached, what they talked about – and also to provide some insights for any other similar initiatives that may follow us in the future

The impact of meteorology on the interannual growth rate of atmospheric methane

The impact of interannual changes in meteorology on the local and global growth rates of atmospheric methane is assessed in a nineteen year simulation using a tropospheric chemical transport model forced by ECMWF meteorological analyses from 1980 to 1998. A very simple CH4 chemistry scheme has been implemented, using prescribed OH fields. There are no interannual variations in modeled methane emissions or in the OH fields, so any changes in the modeled growth rate arise from changes in meteorology. The methane simulation shows significant interannual variability at both local and global scales. The local scale variability is comparable in magnitude to the interannual variability found in surface observations and shows some clear correlation with observed changes in growth rates. This suggests that, even over interannual timescales, meteorology could be important in driving the interannual fluctuations of atmospheric methane at the surface

The dynamics of quantum phases in a spinor condensate

We discuss the quantum phases and their diffusion dynamics in a spinor-1 atomic Bose-Einstein condensate. For ferromagnetic interactions, we obtain the exact ground state distribution of the phases associated with the total atom number ($N$), the total magnetization (${\cal M}$), and the alignment (or hypercharge) ($Y$) of the system. The mean field ground state is stable against fluctuations of atom numbers in each of the spin components, and the phases associated with the order parameter for each spin components diffuse while dynamically recover the two broken continuous symmetries [U(1) and SO(2)] when $N$ and ${\cal M}$ are conserved as in current experiments. We discuss the implications to the quantum dynamics due to an external (homogeneous) magnetic field. We also comment on the case of a spinor-1 condensate with anti-ferromagnetic interactions.Comment: 5 figures, an extended version of cond-mat/030117

Breakdown of superfluidity of an atom laser past an obstacle

The 1D flow of a continuous beam of Bose-Einstein condensed atoms in the presence of an obstacle is studied as a function of the beam velocity and of the type of perturbing potential (representing the interaction of the obstacle with the atoms of the beam). We identify the relevant regimes: stationary/time-dependent and superfluid/dissipative; the absence of drag is used as a criterion for superfluidity. There exists a critical velocity below which the flow is superfluid. For attractive obstacles, we show that this critical velocity can reach the value predicted by Landau's approach. For penetrable obstacles, it is shown that superfluidity is recovered at large beam velocity. Finally, enormous differences in drag occur when switching from repulsive to attractive potential.Comment: 15 pages, 6 figure

Generation of entangled states of two atoms inside a leaky cavity

An in-depth theoretical study is carried out to examine the quasi-deterministic entanglement of two atoms inside a leaky cavity. Two $\Lambda$-type three-level atoms, initially in their ground states, may become maximally entangled through the interaction with a single photon. By working out an exact analytic solution, we show that the probability of success depends crucially on the spectral function of the injected photon. With a cavity photon, one can generate a maximally entangled state with a certain probability that is always less than 50%. However, for an injected photon with a narrower spectral width, this probability can be significantly increased. In particular, we discover situations in which entanglement can be achieved in a single trial with an almost unit probability

Allen Telescope Array Multi-Frequency Observations of the Sun

We present the first observations of the Sun with the Allen Telescope Array (ATA). We used up to six frequencies, from 1.43 to 6 GHz, and baselines from 6 to 300 m. To our knowledge, these are the first simultaneous multifrequency full-Sun maps obtained at microwave frequencies without mosaicing. The observations took place when the Sun was relatively quiet, although at least one active region was present each time. We present multi-frequency flux budgets for each sources on the Sun. Outside of active regions, assuming optically thin bremsstrahlung (free--free) coronal emission on top of an optically thick ~10 000 K chromosphere, the multi-frequency information can be condensed into a single, frequency-independent, "coronal bremsstrahlung contribution function" [EM/sqrt(T)] map. This technique allows the separation of the physics of emission as well as a measurement of the density structure of the corona. Deviations from this simple relationship usually indicate the presence of an additional gyroresonance-emission component, as is typical in active regions.Comment: 16 pages, 11 figures. Accepted for publication in Solar Physic

A modular digital twinning framework for safety assurance of collaborative robotics

Digital twins offer a unique opportunity to design, test, deploy, monitor, and control real-world robotic processes. In this paper we present a novel, modular digital twinning framework developed for the investigation of safety within collaborative robotic manufacturing processes. The modular architecture supports scalable representations of user-defined cyber-physical environments, and tools for safety analysis and control. This versatile research tool facilitates the creation of mixed environments of Digital Models, Digital Shadows, and Digital Twins, whilst standardising communication and physical system representation across different hardware platforms. The framework is demonstrated as applied to an industrial case-study focused on the safety assurance of a collaborative robotic manufacturing process. We describe the creation of a digital twin scenario, consisting of individual digital twins of entities in the manufacturing case study, and the application of a synthesised safety controller from our wider work. We show how the framework is able to provide adequate evidence to virtually assess safety claims made against the safety controller using a supporting validation module and testing strategy. The implementation, evidence and safety investigation is presented and discussed, raising exciting possibilities for the use of digital twins in robotic safety assurance

Disease consequences of higher adiposity uncoupled from its adverse metabolic effects using Mendelian randomisation

Background:Some individuals living with obesity may be relatively metabolically healthy, whilst others suffer from multiple conditions that may be linked to adverse metabolic effects or other factors. The extent to which the adverse metabolic component of obesity contributes to disease compared to the non-metabolic components is often uncertain. We aimed to use Mendelian randomisation (MR) and specific genetic variants to separately test the causal roles of higher adiposity with and without its adverse metabolic effects on diseases.Methods:We selected 37 chronic diseases associated with obesity and genetic variants associated with different aspects of excess weight. These genetic variants included those associated with metabolically ‘favourable adiposity’ (FA) and ‘unfavourable adiposity’ (UFA) that are both associated with higher adiposity but with opposite effects on metabolic risk. We used these variants and two sample MR to test the effects on the chronic diseases.Results:MR identified two sets of diseases. First, 11 conditions where the metabolic effect of higher adiposity is the likely primary cause of the disease. Here, MR with the FA and UFA genetics showed opposing effects on risk of disease: coronary artery disease, peripheral artery disease, hypertension, stroke, type 2 diabetes, polycystic ovary syndrome, heart failure, atrial fibrillation, chronic kidney disease, renal cancer, and gout. Second, 9 conditions where the non-metabolic effects of excess weight (e.g. mechanical effect) are likely a cause. Here, MR with the FA genetics, despite leading to lower metabolic risk, and MR with the UFA genetics, both indicated higher disease risk: osteoarthritis, rheumatoid arthritis, osteoporosis, gastro-oesophageal reflux disease, gallstones, adult-onset asthma, psoriasis, deep vein thrombosis, and venous thromboembolism.Conclusions:Our results assist in understanding the consequences of higher adiposity uncoupled from its adverse metabolic effects, including the risks to individuals with high body mass index who may be relatively metabolically healthy.Funding:Diabetes UK, UK Medical Research Council, World Cancer Research Fund, National Cancer Institute

Disease consequences of higher adiposity uncoupled from its adverse metabolic effects using Mendelian randomisation

Background:Some individuals living with obesity may be relatively metabolically healthy, whilst others suffer from multiple conditions that may be linked to adverse metabolic effects or other factors. The extent to which the adverse metabolic component of obesity contributes to disease compared to the non-metabolic components is often uncertain. We aimed to use Mendelian randomisation (MR) and specific genetic variants to separately test the causal roles of higher adiposity with and without its adverse metabolic effects on diseases.Methods:We selected 37 chronic diseases associated with obesity and genetic variants associated with different aspects of excess weight. These genetic variants included those associated with metabolically ‘favourable adiposity’ (FA) and ‘unfavourable adiposity’ (UFA) that are both associated with higher adiposity but with opposite effects on metabolic risk. We used these variants and two sample MR to test the effects on the chronic diseases.Results:MR identified two sets of diseases. First, 11 conditions where the metabolic effect of higher adiposity is the likely primary cause of the disease. Here, MR with the FA and UFA genetics showed opposing effects on risk of disease: coronary artery disease, peripheral artery disease, hypertension, stroke, type 2 diabetes, polycystic ovary syndrome, heart failure, atrial fibrillation, chronic kidney disease, renal cancer, and gout. Second, 9 conditions where the non-metabolic effects of excess weight (e.g. mechanical effect) are likely a cause. Here, MR with the FA genetics, despite leading to lower metabolic risk, and MR with the UFA genetics, both indicated higher disease risk: osteoarthritis, rheumatoid arthritis, osteoporosis, gastro-oesophageal reflux disease, gallstones, adult-onset asthma, psoriasis, deep vein thrombosis, and venous thromboembolism.Conclusions:Our results assist in understanding the consequences of higher adiposity uncoupled from its adverse metabolic effects, including the risks to individuals with high body mass index who may be relatively metabolically healthy.Funding:Diabetes UK, UK Medical Research Council, World Cancer Research Fund, National Cancer Institute