ROR-γ drives androgen receptor expression and represents a therapeutic target in castration-resistant prostate cancer.

The androgen receptor (AR) is overexpressed and hyperactivated in human castration-resistant prostate cancer (CRPC). However, the determinants of AR overexpression in CRPC are poorly defined. Here we show that retinoic acid receptor-related orphan receptor γ (ROR-γ) is overexpressed and amplified in metastatic CRPC tumors, and that ROR-γ drives AR expression in the tumors. ROR-γ recruits nuclear receptor coactivator 1 and 3 (NCOA1 and NCOA3, also known as SRC-1 and SRC-3) to an AR-ROR response element (RORE) to stimulate AR gene transcription. ROR-γ antagonists suppress the expression of both AR and its variant AR-V7 in prostate cancer (PCa) cell lines and tumors. ROR-γ antagonists also markedly diminish genome-wide AR binding, H3K27ac abundance and expression of the AR target gene network. Finally, ROR-γ antagonists suppressed tumor growth in multiple AR-expressing, but not AR-negative, xenograft PCa models, and they effectively sensitized CRPC tumors to enzalutamide, without overt toxicity, in mice. Taken together, these results establish ROR-γ as a key player in CRPC by acting upstream of AR and as a potential therapeutic target for advanced PCa

RORγ is a targetable master regulator of cholesterol biosynthesis in a cancer subtype.

Tumor subtype-specific metabolic reprogrammers could serve as targets of therapeutic intervention. Here we show that triple-negative breast cancer (TNBC) exhibits a hyper-activated cholesterol-biosynthesis program that is strongly linked to nuclear receptor RORγ, compared to estrogen receptor-positive breast cancer. Genetic and pharmacological inhibition of RORγ reduces tumor cholesterol content and synthesis rate while preserving host cholesterol homeostasis. We demonstrate that RORγ functions as an essential activator of the entire cholesterol-biosynthesis program, dominating SREBP2 via its binding to cholesterol-biosynthesis genes and its facilitation of the recruitment of SREBP2. RORγ inhibition disrupts its association with SREBP2 and reduces chromatin acetylation at cholesterol-biosynthesis gene loci. RORγ antagonists cause tumor regression in patient-derived xenografts and immune-intact models. Their combination with cholesterol-lowering statins elicits superior anti-tumor synergy selectively in TNBC. Together, our study uncovers a master regulator of the cholesterol-biosynthesis program and an attractive target for TNBC

A Perceptron Algorithm for Forest Fire Prediction Based on Wireless Sensor Networks

Forest fire prediction constitutes a significant component of forest management. Timely and accurate forest fire prediction will greatly reduce property and natural losses. A quick method to estimate forest fire hazard levels through known climatic conditions could make an effective improvement in forest fire prediction. This paper presents a description and analysis of a forest fire prediction methods based on machine learning, which adopts WSN (Wireless Sensor Networks) technology and perceptron algorithms to provide a reliable and rapid detection of potential forest fire. Weather data are gathered by sensors, and then forwarded to the server, where a fire hazard index can be calculated

Experimental and numerical study of a two-body heaving wave energy converter with different power take-off models

Wave energy is one of the most difficult energies to be captured among marine renewables. With the technical progress, wave energy converters (WECs) are being tested in relatively deeper waters, which makes floating concepts almost the only choice. In this paper, a two-body heaving WEC where the wave energy is absorbed through the relative motion between the outer annular and the inner cylindrical buoys is studied. Both experimental and numerical studies are adopted for regular wave conditions. In the physical model test, a hydraulic system is used to achieve constant power take-off (PTO) damping force. Numerical simulations, validated against experimental data, are applied using both the frequency domain and the time domains analyses. Different types of PTOs, including constant, linear and nonlinear damping forces, are undertaken to evaluate the hydrodynamic and power absorption performance of such device.acceptedVersio

Computers from plants we never made. Speculations

We discuss possible designs and prototypes of computing systems that could be based on morphological development of roots, interaction of roots, and analog electrical computation with plants, and plant-derived electronic components. In morphological plant processors data are represented by initial configuration of roots and configurations of sources of attractants and repellents; results of computation are represented by topology of the roots' network. Computation is implemented by the roots following gradients of attractants and repellents, as well as interacting with each other. Problems solvable by plant roots, in principle, include shortest-path, minimum spanning tree, Voronoi diagram, $\alpha$-shapes, convex subdivision of concave polygons. Electrical properties of plants can be modified by loading the plants with functional nanoparticles or coating parts of plants of conductive polymers. Thus, we are in position to make living variable resistors, capacitors, operational amplifiers, multipliers, potentiometers and fixed-function generators. The electrically modified plants can implement summation, integration with respect to time, inversion, multiplication, exponentiation, logarithm, division. Mathematical and engineering problems to be solved can be represented in plant root networks of resistive or reaction elements. Developments in plant-based computing architectures will trigger emergence of a unique community of biologists, electronic engineering and computer scientists working together to produce living electronic devices which future green computers will be made of.Comment: The chapter will be published in "Inspired by Nature. Computing inspired by physics, chemistry and biology. Essays presented to Julian Miller on the occasion of his 60th birthday", Editors: Susan Stepney and Andrew Adamatzky (Springer, 2017

Power Absorption of A Two-Body Heaving Wave Energy Converter Considering Different Control and Power Take-off Systems

This study proposed a wave power system with two coaxial floating cylinders of different diameters and drafts. Wavebob’s conceptual design has been adopted in the wave power system. In this study, a basic analysis of the wave energy extraction by the relative motion between two floats is presented. The maximum power absorption was studied theoretically under regular wave conditions, and the effects of both linear and constant damping forces on the power take-off (PTO) were investigated. A set of dynamic equations describing the floats’ displacement under regular waves and different PTOs are established. A time-domain numerical model is developed, considering the PTO parameter and viscous damping, and the optimal PTO damping and output power are obtained. With the analysis of estimating the maximum power absorption, a new estimation method called Power Capture Function (PCF) is proposed and constructed, which can be used to predict the power capture under both linear and constant PTO forces. Based on this, energy extraction is analyzed and optimized. Finally, the performance characteristics of the two-body power system are concluded.acceptedVersio

Maximum Data Generation Rate Routing Protocol Based on Data Flow Controlling Technology for Rechargeable Wireless Sensor Networks

For rechargeable wireless sensor networks, limited energy storage capacity, dynamic energy supply, low and dynamic duty cycles cause that it is unpractical to maintain a fixed routing path for packets delivery permanently from a source to destination in a distributed scenario. Therefore, before data delivery, a sensor has to update its waking schedule continuously and share them to its neighbors, which lead to high energy expenditure for reestablishing path links frequently and low efficiency of energy utilization for collecting packets. In this work, we propose the maximum data generation rate routing protocol based on data flow controlling technology. For a sensor, it does not share its waking schedule to its neighbors and cache any waking schedules of other sensors. Hence, the energy consumption for time synchronization, location information and waking schedule shared will be reduced significantly. The saving energy can be used for improving data collection rate. Simulation shows our scheme is efficient to improve packets generation rate in rechargeable wireless sensor networks

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Identification of a CTRP9 C-Terminal polypeptide capable of enhancing bone-derived mesenchymal stem cell cardioprotection through promoting angiogenic exosome production.

BACKGROUND: Mesenchymal stem cell therapy improves ischemic heart failure via incompletely understood mechanisms. C1q-TNFα related protein-9 (CTRP9) is a novel anti-oxidative cardiokine capable of improving the local microenvironment and cell survival by its c-terminal active globular domain (gCTRP9). The current study attempted to: 1) identify active gCTRP9 c-terminal polypeptides with stem cell protective function; 2) determine whether a lead polypeptide may enable/enhance cortical bone-derived mesenchymal stem cell (CBSC) cardioprotection against post-myocardial infarction (post-MI) remodeling; and 3) define the responsible underlying cellular/molecular mechanisms. METHODS AND RESULTS: Utilizing I-TASSER structure prediction and 3-D active site modeling, we cloned and purified 3 gCTRP9 fragments (CTRP9-237, CTRP9-277, and CTRP9-281). Their activation of cell salvage kinase was compared against gCTRP9. Among the three fragments, CTRP9-281 (a 45 residue-containing polypeptide) exerted comparable or greater ERK1/2 activation compared to gCTRP9. Treatment with CTRP9-281 or gCTRP9 significantly increased CBSC proliferation and migration, and attenuated oxidative stress-induced CBSC apoptosis. CTRP9-281 and gCTRP9 comparably upregulated SOD2 and SOD3 expression. However, CTRP9-281, not gCTRP9, upregulated FGF2 and VEGFA expression/secretion in an ERK1/2 dependent manner. Administration of gCTRP9 or CTRP9-281 alone attenuated post-MI cardiac dysfunction and improved CBSC retention in the infarcted heart in similar fashion. However, CTRP9-281 exerted greater synergistic effect with CBSC than gCTRP9 related to pro-angiogenic, anti-fibrotic, and anti-remodeling effects. Mechanistically, CTRP9-281 significantly increased SOD2-rich and VEGFA-rich exosome production by CBSC. Exosomes from CTRP9-281 treated CBSC significantly attenuated oxidative stress-induced cardiomyocyte apoptosis in vitro. An exosome generation inhibitor attenuated CTRP9-281 enhancement of CBSC cardioprotection in vivo. CONCLUSION: We identified a CTRP9 polypeptide that upregulates SOD2/SOD3 expression and improves CBSC survival/retention, similar to gCTRP9. Moreover, CTRP9-281 stimulates VEGFA-rich exosome production by CBSC, exerting superior pro-angiogenic, anti-fibrotic, and cardioprotective actions