ATRA mechanically reprograms pancreatic stellate cells to suppress matrix remodelling and inhibit cancer cell invasion

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a dismal survival rate. Persistent activation of pancreatic stellate cells (PSCs) can perturb the biomechanical homoeostasis of the tumour microenvironment to favour cancer cell invasion. Here we report that ATRA, an active metabolite of vitamin A, restores mechanical quiescence in PSCs via a mechanism involving a retinoic acid receptor beta (RAR-β)-dependent downregulation of actomyosin (MLC-2) contractility. We show that ATRA reduces the ability of PSCs to generate high traction forces and adapt to extracellular mechanical cues (mechanosensing), as well as suppresses force-mediated extracellular matrix remodelling to inhibit local cancer cell invasion in 3D organotypic models. Our findings implicate a RAR-β/MLC-2 pathway in peritumoural stromal remodelling and mechanosensory-driven activation of PSCs, and further suggest that mechanical reprogramming of PSCs with retinoic acid derivatives might be a viable alternative to stromal ablation strategies for the treatment of PDAC

Reconstructing the Complete Patent Bargain: The Doctrine of Equivalents

This paper provides a theoretical justification for the doctrine of equivalents in patent law that is based on the contractarian view of the patent grant

Exceptions to Trade Mark Exhaustion: Inalienability Rules for the Protection of Reputational Economic Value

This article analyses the exceptions to the principle of exhaustion of trade mark rights from the perspective of the functions theory and the concept of inalienability rules. Despite its traditional hostility towards the imposition of restrictions to the alienation of chattels, the law often chooses to protect entitlements through inalienability rules with a view to achieving economic efficiency

Wave interaction with defects in pressurised composite structures

There exists a great variety of structural failure modes which must be frequently inspected to ensure continuous structural integrity of composite structures. This work presents a Finite Element (FE) based method for calculating wave interaction with damage within structures of arbitrary layering and geometric complexity. The principal novelty is the investigation of pre-stress effect on wave propagation and scattering in layered structures. A Wave Finite Element (WFE) method, which combines FE analysis with periodic structure theory (PST), is used to predict the wave propagation properties along periodic waveguides of the structural system. This is then coupled to the full FE model of a coupling joint within which structural damage is modelled, in order to quantify wave interaction coeffcients through the joint. Pre-stress impact is quantified by comparison of results under pressurised and non-pressurised scenarios. The results show that including these pressurisation effects in calculations is essential. This is of specific relevance to aircraft structures being intensely pressurised while on air. Numerical case studies are exhibited for different forms of damage type. The exhibited results are validated against available analytical and experimental results

African Americans, Gentrification, and Neoliberal Urbanization: the Case of Fort Greene, Brooklyn

This article examines the gentrification of Fort Greene, which is located in the western part of black Brooklyn, one of the largest contiguous black urban areas in the USA. Between the late 1960s and 2003, gentrification in Fort Greene followed the patterns discovered by scholars of black neighborhoods; the gentrifying agents were almost exclusively black and gentrification as a process was largely bottom-up because entities interested in the production of space were mostly not involved. Since 2003, this has changed. Whites have been moving to Fort Greene in large numbers and will soon represent the numerical majority. Public and private interventions in and around Fort Greene have created a new top-down version of gentrification, which is facilitating this white influx. Existing black residential and commercial tenants are replaced and displaced in the name of urban economic development

An artificial neural network model application for the estimation of thermal comfort conditions in mountainous regions, Greece

In this research, an artificial neural network model (ANN) was applied to estimate the thermal comfort conditions in the mountainous regions of Gerania (MG) and of Nafpaktia (MN) in Greece. Air temperature and relative humidity were recorded from June to August 2007 at two selected sites for each study region. Data of the aforementioned parameters were used for the calculation of the thermohygrometric index (THI), from which thermal comfort conditions were evaluated as classes. The ANN model, the multilayer perceptron (MLP) was used for the estimation of THI values at the examined high altitude level (1334 and 1338 m in MG and MN, respectively) based on the temperature and the relative humidity of the examined low altitude level (650 m in MG and 676 m in MN), taking into account the actual time of measurement (ATM). The results of the development and application of this extended MLP model indicated more accurate estimations of THI values at the two study regions during the whole day period compared to the MLP application without the use of ATM. Also, the extended model, examining the whole day, showed more accurate estimations of THI values in MG compared to MN. Similarly, this model provided better estimations separately for both daytime (09h00min-20h00min) and nighttime (21h00min-08h00min) in comparison with the respective THI estimations taking into account only the air temperature and relative humidity as input parameters. Additionally, the extended MLP model was more efficient estimating THI values during daytime hours compared to nighttime hours in both MG and MN. Also, the extended MLP model was more capable in estimating better the THI values in the “hot” class in MG as well as in the “comfortable” class in MN.En esta investigación, se aplicó un modelo de red neuronal artificial (ANN), para estimar las condiciones térmicas de las regiones montañosas de Gerania (MG) y de Nafpaktia (MN) en Grecia. La temperatura del aire y la humedad relativa fueron registradas de junio hasta agosto de 2007, en dos sitios seleccionados de cada región estudiada. Datos de los parámetros antes mencionados se usaron para calcular el índice termohigrométrico (THI), evaluando las condiciones de confort térmico como categorías. El modelo ANN, perceptrón multicapa (MLP), fue usado para estimar los valores del THI en los niveles de las alturas 1334 y 1338 m en MG y MN, respectivamente. Con base en la temperatura y en la humedad relativa de los niveles examinados a baja altitud (650 m en MG y 676 m en MN), teniendo en cuenta el tiempo de medición real (ATM). Los resultados del desarrollo y aplicación del modelo ampliado MLP indicaron una estimación más precisa de los valores THI en los estudios de las dos regiones durante un periodo de todo el día, comparado con la aplicación MLP sin el uso del ATM. También, el modelo ampliado, examinando el día entero, mostró estimaciones más precisas de los valores THI en el MG comparados con el MN. De manera similar, este modelo proporcionó una mejor estimación por separado del periodo, tanto durante el día (09h00min-20h00min) y durante la noche (21h00min-08h00min) en comparación con las estimaciones respectivas del THI, tomando en cuenta sólo la temperatura del aire y la humedad relativa como parámetros de entrada. Adicionalmente, la ampliación del modelo MLP fue mucho más eficiente para estimar los valores THI durante las horas del día, comparado con las horas de la noche en ambos MG y MN. También el modelo ampliado MLP fue capaz de estimar mejor los valores de THI en la clase Caliente en MG, como así mismo en la clase Confortable en MN

Distributed Power Control in Wireless Communication Systems

Energy efficiency is a measure of performance in wireless networks. Therefore, controlling the transmitter power at a given node increases not only battery operating life, but also overall system capacity by successfully admitting new links. It is essential to find effective means of power control in point-to-point, broadcasting and multicasting scenarios. Wireless networking presents formidable challenges, and we consider the problem of unicast or point-to-point (peer-to-peer) communication in wireless networks in the presence of other nodes. We study the feasibility of admitting new links in an wireless network operating area while maintaining quality of service (QoS), in terms of signal-to-interference ratio (SIR), for each link. SIR is maintained by adjusting the transmitter power levels at each source for a given link. Distributed power control (DPC) is a natural choice for this purpose because, unlike centralized power control, DPC should be able to adjust the power levels of each transmitted signal using local measurements, so that in a reasonable time, all nodes/links maintain the desired SIR. We present a suite of DPC schemes using both state space and optimal control methodology in discrete time. Further, we prove the convergence of the overall network with our algorithm using Lyapunov stability analysis in comparison with a well-known DPC scheme (see Bambos, N. et al., IEEE ACM Trans. on Networking, p.583-97, 2000). We present simulation results and comparisons for point-to-point communications in an overlapping scenario