Phase I/II study of the deacetylase inhibitor panobinostat after allogeneic stem cell transplantation in patients with high-risk MDS or AML (PANOBEST trial)

Maintenance therapy after allogeneic hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) is conceptually attractive to prevent relapse, but has been hampered by the limited number of suitable anti-leukemic agents. The deacetylase inhibitor (DACi) panobinostat demonstrated moderate anti-leukemic activity in a small subset of patients with advanced AML and high-risk MDS in phase I/II trials.1, 2 It also displays immunomodulatory activity3 that may enhance leukemia-specific cytotoxicity4 and mitigate graft versus host disease (GvHD), but conversely could impair T- and NK cell function.5, 6 We conducted this open-label, multi-center phase I/II trial (NCT01451268) to assess the feasibility and preliminary efficacy of prolonged prophylactic administration of panobinostat after HSCT for AML or MDS. The study protocol was approved by an independent ethics committee and conducted in compliance with the Declaration of Helsinki. All patients provided written informed consent. ..

Fractional quantum Hall effect in the absence of Landau levels

It has been well-known that topological phenomena with fractional excitations, i.e., the fractional quantum Hall effect (FQHE) \cite{Tsui1982} will emerge when electrons move in Landau levels. In this letter, we report the discovery of the FQHE in the absence of Landau levels in an interacting fermion model. The non-interacting part of our Hamiltonian is the recently proposed topologically nontrivial flat band model on the checkerboard lattice \cite{sun}. In the presence of nearest-neighboring repulsion ($U$), we find that at 1/3 filling, the Fermi-liquid state is unstable towards FQHE. At 1/5 filling, however, a next-nearest-neighboring repulsion is needed for the occurrence of the 1/5 FQHE when $U$ is not too strong. We demonstrate the characteristic features of these novel states and determine the phase diagram correspondingly.Comment: 6 pages and 4 figure

Super-Eddington accretion on to the neutron star NGC7793 P13: Broad-band X-ray spectroscopy and ultraluminous X-ray sources

We present a detailed, broad-band X-ray spectral analysis of the ultraluminous X-ray source (ULX) pulsar NGC 7793 P13, a known super-Eddington source, utilizing data from the XMM–Newton, NuSTAR and Chandra observatories. The broad-band XMM–Newton+NuSTAR spectrum of P13 is qualitatively similar to the rest of the ULX sample with broad-band coverage, suggesting that additional ULXs in the known population may host neutron star accretors. Through time-averaged, phase-resolved and multi-epoch studies, we find that two non-pulsed thermal blackbody components with temperatures ∼0.5 and 1.5 keV are required to fit the data below 10 keV, in addition to a third continuum component which extends to higher energies and is associated with the pulsed emission from the accretion column. The characteristic radii of the thermal components appear to be comparable, and are too large to be associated with the neutron star itself, so the need for two components likely indicates the accretion flow outside the magnetosphere is complex. We suggest a scenario in which the thick inner disc expected for super-Eddington accretion begins to form, but is terminated by the neutron star's magnetic field soon after its onset, implying a limit of B ≲ 6 × 1012 G for the dipolar component of the central neutron star's magnetic field. Evidence of similar termination of the disc in other sources may offer a further means of identifying additional neutron star ULXs. Finally, we examine the spectrum exhibited by P13 during one of its unusual ‘off’ states. These data require both a hard power-law component, suggesting residual accretion on to the neutron star, and emission from a thermal plasma, which we argue is likely associated with the P13 system

Radioprotective Effect of American Ginseng on Human Lymphocytes at 90 Minutes Post-irradiation: A Study of 40 Cases

Backgroundâ Ionizing radiation (IR) initiates intracellular oxidative stress through enhanced formation of reactive oxygen species (ROS) that attack DNA leading to cell death. As the diversity of IR applied in medicine, agriculture, industry, and the growing threats of global terrorism, the acquisition of radioprotectors is an urgent need for the nation. However, the applicability of radioprotectors currently under investigation is limited due to their inherent toxicity. Objectiveâ This study investigated the effect of a standardized North American ginseng extract (NAGE, total ginsenoside content: 11.7%) on DNA damage in human lymphocytes at 90 min postirradiation. Designâ With the application of NAGE (250 â 1000 μg mlâ 1) at 90 min post-irradiation (1 and 2 Gy), DNA damage in lymphocytes obtained from 40 healthy individuals was evaluated by cytokinesis-block micronucleus (CBMN) assay. Similar experiments were also performed in lymphocytes treated with WR-1065 (1 mM or 3mM). In addition, before and after irradiation, lymphocytes obtained from 10 individuals were measured for their total antioxidant capacity (TAC) and the reactive oxygen species (ROS). Resultsâ The significant effect of NAGE against 137Cs-induced MN in lymphocytes is concentration-dependent. NAGE (750 μg mlâ 1) reduced MN yield by 50.7% after 1 Gy and 35.9% after 2 Gy exposures, respectively; these results were comparable to that of WR-1065. Further, we also found that NAGE reduces MN yield and ROS but increases TAC in lymphocytes. Conclusionsâ Our results suggest that NAGE is a relatively non-toxic natural compound that holds radioprotective potential in human lymphocytes even when applied at 90 min post-irradiation. One of the radioprotective mechanisms may be mediated through the scavenging of free radicals and enhancement of the intracellular TAC. Originally published Journal of Alternative and Complementary Medicine Vol. 16, No. 5 2010

A review of physical supply and EROI of fossil fuels in China

This paper reviews China’s future fossil fuel supply from the perspectives of physical output and net energy output. Comprehensive analyses of physical output of fossil fuels suggest that China’s total oil production will likely reach its peak, at about 230 Mt/year (or 9.6 EJ/year), in 2018; its total gas production will peak at around 350 Bcm/year (or 13.6 EJ/year) in 2040, while coal production will peak at about 4400 Mt/year (or 91.9 EJ/year) around 2020 or so. In terms of the forecast production of these fuels, there are significant differences among current studies. These differences can be mainly explained by different ultimately recoverable resources assumptions, the nature of the models used, and differences in the historical production data. Due to the future constraints on fossil fuels production, a large gap is projected to grow between domestic supply and demand, which will need to be met by increasing imports. Net energy analyses show that both coal and oil and gas production show a steady declining trend of EROI (energy return on investment) due to the depletion of shallow-buried coal resources and conventional oil and gas resources, which is generally consistent with the approaching peaks of physical production of fossil fuels. The peaks of fossil fuels production, coupled with the decline in EROI ratios, are likely to challenge the sustainable development of Chinese society unless new abundant energy resources with high EROI values can be found

Thin film Gallium nitride (GaN) based acoustofluidic Tweezer: Modelling and microparticle manipulation.

Gallium nitride (GaN) is a compound semiconductor which shows advantages in new functionalities and applications due to its piezoelectric, optoelectronic, and piezo-resistive properties. This study develops a thin film GaN-based acoustic tweezer (GaNAT) using surface acoustic waves (SAWs) and demonstrates its acoustofluidic ability to pattern and manipulate microparticles. Although the piezoelectric performance of the GaNAT is compromised compared with conventional lithium niobate-based SAW devices, the inherited properties of GaN allow higher input powers and superior thermal stability. This study shows for the first time that thin film GaN is suitable for the fabrication of the acoustofluidic devices to manipulate microparticles with excellent performance. Numerical modelling of the acoustic pressure fields and the trajectories of mixtures of microparticles driven by the GaNAT was performed and the results were verified from the experimental studies using samples of polystyrene microspheres. The work has proved the robustness of thin film GaN as a candidate material to develop high-power acoustic tweezers, with the potential of monolithical integration with electronics to offer diverse microsystem applications.Engineering and Physical Sciences Research Council Grant numbers: EP/P002803/1, EP/P018998/1, Natural Science Basic Research Program of Shaanxi Province/2020JQ-233, Fundamental Scientific Research of Central Universities/3102017OQD116, Engineering and Physical Sciences Research Council fellowship /EP/N01202X/2, Royal Society / IEC/NSFC/170142, IE161019, Natural Science Foundation of China/61704017, Dalian Science and Technology Innovation Fund/2018J11CY00

Cell-based expression cloning for identification of polypeptides that hypersensitize mammalian cells to mitotic arrest

Microtubule inhibitors such as Vinblastine and Paclitaxel are chemotherapy agents that activate the mitotic spindle checkpoint, arresting cells in mitosis and leading to cell death. The pathways that connect mitotic arrest to cell death are not well characterized. We developed a mammalian cell-based cDNA cloning method to isolate proteins and protein fragments whose expression inhibits colony formation in the presence of microtubule inhibitors. Understanding how these proteins impact cellular responses to microtubule drugs will lead to better understanding of the biochemical pathways connecting mitotic arrest and cell death in mammalian cells and may provide novel targets that can enhance microtubule inhibitor-mediated chemotherapy

Kernelized Multiview Projection for Robust Action Recognition

Conventional action recognition algorithms adopt a single type of feature or a simple concatenation of multiple features. In this paper, we propose to better fuse and embed different feature representations for action recognition using a novel spectral coding algorithm called Kernelized Multiview Projection (KMP). Computing the kernel matrices from different features/views via time-sequential distance learning, KMP can encode different features with different weights to achieve a low-dimensional and semantically meaningful subspace where the distribution of each view is sufficiently smooth and discriminative. More crucially, KMP is linear for the reproducing kernel Hilbert space, which allows it to be competent for various practical applications. We demonstrate KMP’s performance for action recognition on five popular action datasets and the results are consistently superior to state-of-the-art techniques

Emergence of scale-free leadership structure in social recommender systems

The study of the organization of social networks is important for understanding of opinion formation, rumor spreading, and the emergence of trends and fashion. This paper reports empirical analysis of networks extracted from four leading sites with social functionality (Delicious, Flickr, Twitter and YouTube) and shows that they all display a scale-free leadership structure. To reproduce this feature, we propose an adaptive network model driven by social recommending. Artificial agent-based simulations of this model highlight a "good get richer" mechanism where users with broad interests and good judgments are likely to become popular leaders for the others. Simulations also indicate that the studied social recommendation mechanism can gradually improve the user experience by adapting to tastes of its users. Finally we outline implications for real online resource-sharing systems