Targeting AKT/mTOR Signaling Pathways During Murine Skin Tumor Promotion and the Impact of Dietary Energy Balance Manipulation

The prevalence of obesity has continued to rise over the last several decades in the United States lending to overall increases in risk for chronic diseases including many types of cancer. In contrast, reduction in energy consumption via calorie restriction (CR) has been shown to be a potent inhibitor of carcinogenesis across a broad range of species and tumor types. Previous data has demonstrated differential signaling through Akt and mTOR via the IGF-1R and other growth factor receptors across the diet-induced obesity (DIO)/CR spectrum. Furthermore, mTORC1 is known to be regulated directly via nutrient availability, supporting its role in the link between epithelial carcinogenesis and diet-induced obesity. In an effort to better understand the importance of mTORC1 in the context of both positive and negative energy balance during epithelial carcinogenesis, we have employed the use of specific pharmacological inhibitors, rapamycin (mTORC1 inhibitor) and metformin (AMPK activator) to target mTORC1 or various components of this pathway during skin tumor promotion. Two-stage skin carcinogenesis studies demonstrated that mTORC1 inhibition via rapamycin, metformin or combination treatments greatly inhibited skin tumor development in normal, overweight and obese mice. Furthermore, mechanisms by which these chemopreventive agents may be exerting their anti-tumor effects were explored. In addition, the effect of these compounds on the epidermal proliferative response was analyzed and drastic decreases in epidermal hyperproliferation and hyperplasia were found. Rapamycin also inhibited dermal inflammatory cell infiltration in a dose-dependent manner. Both compounds also blocked or attenuated TPA-induced signaling through epidermal mTORC1 as well as several downstream targets. In addition, inhibition of this pathway by metformin appeared to be, at least in part, dependent on AMPK activation in the skin. Overall, the data indicate that pharmacological strategies targeting this pathway offset the tumor-enhancing effects of DIO and may serve as possible CR mimetics. They suggest that mTORC1 contributes significantly to the process of skin tumor promotion, specifically during dietary energy balance effects. Exploiting the mechanistic information underlying dietary energy balance responsive pathways will help translate decades of research into effective strategies for prevention of epithelial carcinogenesis.

Over-determined charbonate chemstry dataset from different kinds of manipulation (TA, DIC) and water types (natural and artificial seawater)

The growing field of ocean acidification research is concerned with the investigation of organism responses to increasing pCO2 values. One important approach in this context is culture work using seawater with adjusted CO2 levels. As aqueous pCO2 is difficult to measure directly in small-scale experiments, it is generally calculated from two other measured parameters of the carbonate system (often AT, CT or pH). Unfortunately, the overall uncertainties of measured and subsequently calculated values are often unknown. Especially under high pCO2, this can become a severe problem with respect to the interpretation of physiological and ecological data. In the few datasets from ocean acidification research where all three of these parameters were measured, pCO2 values calculated from AT and CT are typically about 30% lower (i.e. ~300 µatm at a target pCO2 of 1000 µatm) than those calculated from AT and pH or CT and pH. This study presents and discusses these discrepancies as well as likely consequences for the ocean acidification community. Until this problem is solved, one has to consider that calculated parameters of the carbonate system (e.g. pCO2, calcite saturation state) may not be comparable between studies, and that this may have important implications for the interpretation of CO2 perturbation experiments.

Mesocosm experiment Cape Verde 2012: Data

Two 7-day mesocosm experiments were conducted in October 2012 at the Instituto Nacional de Desenvolvimento das Pescas (INDP), Mindelo, Cape Verde. Surface water was collected at night before the start of the respective experiment with RV Islândia south of São Vicente (16°44.4'N, 25°09.4'W) and transported to shore using four 600L food safe intermediate bulk containers. Sixteen mesocosm bags were distributed in four flow-through water baths and shaded with blue, transparent lids to approximately 20% of surface irradiation. Mesocosm bags were filled from the containers by gravity, using a submerged hose to minimize bubbles. The accurate volume inside the individual bags was calculated after addition of 1.5 mmol silicate and measuring the resulting silicate concentration. The volume ranged from 105.5 to 145 L. The experimental manipulation comprised addition of different amounts of inorganic N and P. In the first experiment, the P supply was changed at constant N supply in thirteen of the sixteen units, while in the second experiment the N supply was changed at constant P supply in twelve of the sixteen units. In addition to this, "cornerpoints" were chosen that were repeated during both experiments. Four cornerpoints should have been repeated, but setting the nutrient levels in one mesocosm was not succesfull and therefore this mesocosm also was set at the center point conditions. Experimental treatments were evenly distributed between the four water baths. Initial sampling of the mesocosms on day 1 of each run was conducted between 9:45 and 11:30. After nutrient manipulation, sampling was conducted on a daily basis between 09:00 and 10:30 for days 2 to 8.

Phytoplankton responses and associated carbon cycling during shipboard carbonate chemistry manipulation experiments conducted around Northwest European shelf seas

The ongoing oceanic uptake of anthropogenic carbon dioxide (CO2) is significantly altering the carbonate chemistry of seawater, a phenomenon referred to as ocean acidification. Experimental manipulations have been increasingly used to gauge how continued ocean acidification will potentially impact marine ecosystems and their associated biogeochemical cycles in the future; however, results amongst studies, particularly when performed on natural communities, are highly variable, which may reflect community/environment-specific responses or inconsistencies in experimental approach. To investigate the potential for identification of more generic responses and greater experimentally reproducibility, we devised and implemented a series (n = 8) of short-term (2-4 days) multi-level (>=4 conditions) carbonate chemistry/nutrient manipulation experiments on a range of natural microbial communities sampled in Northwest European shelf seas. Carbonate chemistry manipulations and resulting biological responses were found to be highly reproducible within individual experiments and to a lesser extent between geographically separated experiments. Statistically robust reproducible physiological responses of phytoplankton to increasing pCO2, characterised by a suppression of net growth for small-sized cells (<10 µm), were observed in the majority of the experiments, irrespective of natural or manipulated nutrient status. Remaining between-experiment variability was potentially linked to initial community structure and/or other site-specific environmental factors. Analysis of carbon cycling within the experiments revealed the expected increased sensitivity of carbonate chemistry to biological processes at higher pCO2 and hence lower buffer capacity. The results thus emphasise how biogeochemical feedbacks may be altered in the future ocean.

Intrusion-Resilient Integrity in Data-Centric Unattended WSNs

Unattended Wireless Sensor Networks (UWSNs) operate in autonomous or disconnected mode: sensed data is collected periodically by an itinerant sink. Between successive sink visits, sensor-collected data is subject to some unique vulnerabilities. In particular, while the network is unattended, a mobile adversary (capable of subverting up to a fraction of sensors at a time) can migrate between compromised sets of sensors and inject fraudulent data. In this paper, we provide two collaborative authentication techniques that allow an UWSN to maintain integrity and authenticity of sensor data-in the presence of a mobile adversary-until the next sink visit. Proposed schemes use simple, standard, and inexpensive symmetric cryptographic primitives, coupled with key evolution and few message exchanges. We study their security and effectiveness, both analytically and via simulations. We also assess their robustness and show how to achieve the desired trade-off between performance and security.

Parallel and Distributed Data Management. Introduction

The manipulation and handling of an ever increasing volume of data by current data-intensive applications require novel techniques for e?cient data management. Despite recent advances in every aspect of data management (storage, access, querying, analysis, mining), future applications are expected to scale to even higher degrees, not only in terms of volumes of data handled but also in terms of users and resources, often making use of multiple, pre-existing autonomous, distributed or heterogeneous resources.

Sea Bottom Classification by Means of Bathymetric LIDAR Data

Light Detection and Ranging (LIDAR) provides high horizontal and vertical resolution of spatial data located in point cloud images, and is increasingly being used in a number of applications and disciplines, which have concentrated on the exploit and manipulation of the data using mainly its three dimensional nature. Bathymetric LIDAR systems and data are mainly focused to map depths in shallow and clear waters with a high degree of accuracy. Additionally, the backscattering produced by the different materials distributed over the bottom surface causes that the returned intensity signal contains important information about the reflection properties of these materials. Processing conveniently these values using a Simplified Radiative Transfer Model, allows the identification of different sea bottom types. This paper presents an original method for the classification of sea bottom by means of information processing extracted from the images generated through LIDAR data. The results are validated using a vector database containing benthic information derived by marine surveys.

Control framework for dexterous manipulation using dynamic visual servoing and tactile sensors’ feedback

Tactile sensors play an important role in robotics manipulation to perform dexterous and complex tasks. This paper presents a novel control framework to perform dexterous manipulation with multi-fingered robotic hands using feedback data from tactile and visual sensors. This control framework permits the definition of new visual controllers which allow the path tracking of the object motion taking into account both the dynamics model of the robot hand and the grasping force of the fingertips under a hybrid control scheme. In addition, the proposed general method employs optimal control to obtain the desired behaviour in the joint space of the fingers based on an indicated cost function which determines how the control effort is distributed over the joints of the robotic hand. Finally, authors show experimental verifications on a real robotic manipulation system for some of the controllers derived from the control framework.

Fénix: a flexible information exchange data model for natural language processing

In this paper we describe Fénix, a data model for exchanging information between Natural Language Processing applications. The format proposed is intended to be flexible enough to cover both current and future data structures employed in the field of Computational Linguistics. The Fénix architecture is divided into four separate layers: conceptual, logical, persistence and physical. This division provides a simple interface to abstract the users from low-level implementation details, such as programming languages and data storage employed, allowing them to focus in the concepts and processes to be modelled. The Fénix architecture is accompanied by a set of programming libraries to facilitate the access and manipulation of the structures created in this framework. We will also show how this architecture has been already successfully applied in different research projects.

3D Visual Data-Driven Spatiotemporal Deformations for Non-Rigid Object Grasping Using Robot Hands

Sensing techniques are important for solving problems of uncertainty inherent to intelligent grasping tasks. The main goal here is to present a visual sensing system based on range imaging technology for robot manipulation of non-rigid objects. Our proposal provides a suitable visual perception system of complex grasping tasks to support a robot controller when other sensor systems, such as tactile and force, are not able to obtain useful data relevant to the grasping manipulation task. In particular, a new visual approach based on RGBD data was implemented to help a robot controller carry out intelligent manipulation tasks with flexible objects. The proposed method supervises the interaction between the grasped object and the robot hand in order to avoid poor contact between the fingertips and an object when there is neither force nor pressure data. This new approach is also used to measure changes to the shape of an object’s surfaces and so allows us to find deformations caused by inappropriate pressure being applied by the hand’s fingers. Test was carried out for grasping tasks involving several flexible household objects with a multi-fingered robot hand working in real time. Our approach generates pulses from the deformation detection method and sends an event message to the robot controller when surface deformation is detected. In comparison with other methods, the obtained results reveal that our visual pipeline does not use deformations models of objects and materials, as well as the approach works well both planar and 3D household objects in real time. In addition, our method does not depend on the pose of the robot hand because the location of the reference system is computed from a recognition process of a pattern located place at the robot forearm. The presented experiments demonstrate that the proposed method accomplishes a good monitoring of grasping task with several objects and different grasping configurations in indoor environments.

The New EU Criminal Law Competence in Action: The Proposal for a Directive on Criminal Sanctions for Insider Dealing and Market Manipulation. IES WORKING PAPER 5/2013

The aim of this paper is to analyse the proposed Directive on criminal sanctions for insider dealing and market manipulation (COM(2011)654 final), which represents the first exercise of the European Union competence provided for by Article 83(2) of the Treaty on the Functioning of the European Union. The proposal aims at harmonising the sanctioning regimes provided by the Member States for market abuse, imposing the introduction of criminal sanctions and providing an opportunity to critically reflect on the position taken by the Commission towards the use of criminal law. The paper will discuss briefly the evolution of the EU’s criminal law competence, focusing on the Lisbon Treaty. It will analyse the ‘essentiality standard’ for the harmonisation of criminal law included in Article 83(2) TFEU, concluding that this standard encompasses both the subsidiarity and the ultima ratio principles and implies important practical consequences for the Union’s legislator. The research will then focus on the proposed Directive, trying to assess if the Union’s legislator, notwithstanding the ‘symbolic’ function of this proposal in the financial crisis, provides consistent arguments on the respect of the ‘essentiality standard’. The paper will note that the proposal raises some concerns, because of the lack of a clear reliance on empirical data regarding the essential need for the introduction of criminal law provisions. It will be stressed that only the assessment of the essential need of an EU action, according to the standard set in Article 83(2) TFEU, can guarantee a coherent choice of the areas interested by the harmonisation process, preventing the legislator to choose on the basis of other grounds.

Essays on Procurement, Scoring Auction, and Quality Manipulation Corruption

Thesis (Ph.D.)--University of Washington, 2016-06

Using secondary knowledge to support decision tree classification of retrospective clinical data

Retrospective clinical data presents many challenges for data mining and machine learning. The transcription of patient records from paper charts and subsequent manipulation of data often results in high volumes of noise as well as a loss of other important information. In addition, such datasets often fail to represent expert medical knowledge and reasoning in any explicit manner. In this research we describe applying data mining methods to retrospective clinical data to build a prediction model for asthma exacerbation severity for pediatric patients in the emergency department. Difficulties in building such a model forced us to investigate alternative strategies for analyzing and processing retrospective data. This paper describes this process together with an approach to mining retrospective clinical data by incorporating formalized external expert knowledge (secondary knowledge sources) into the classification task. This knowledge is used to partition the data into a number of coherent sets, where each set is explicitly described in terms of the secondary knowledge source. Instances from each set are then classified in a manner appropriate for the characteristics of the particular set. We present our methodology and outline a set of experiential results that demonstrate some advantages and some limitations of our approach. © 2008 Springer-Verlag Berlin Heidelberg.

Three-dimensional capture, representation, and manipulation of Cuneiform tablets

This paper presents the digital imaging results of a collaborative research project working toward the generation of an on-line interactive digital image database of signs from ancient cuneiform tablets. An important aim of this project is the application of forensic analysis to the cuneiform symbols to identify scribal hands. Cuneiform tablets are amongst the earliest records of written communication, and could be considered as one of the original information technologies; an accessible, portable and robust medium for communication across distance and time. The earliest examples are up to 5,000 years old, and the writing technique remained in use for some 3,000 years. Unfortunately, only a small fraction of these tablets can be made available for display in museums and much important academic work has yet to be performed on the very large numbers of tablets to which there is necessarily restricted access. Our paper will describe the challenges encountered in the 2D image capture of a sample set of tablets held in the British Museum, explaining the motivation for attempting 3D imaging and the results of initial experiments scanning the smaller, more densely inscribed cuneiform tablets. We will also discuss the tractability of 3D digital capture, representation and manipulation, and investigate the requirements for scaleable data compression and transmission methods. Additional information can be found on the project website: www.cuneiform.net

Web-based report generators, data visualization, and Web-to-database connectivity

Because some Web users will be able to design a template to visualize information from scratch, while other users need to automatically visualize information by changing some parameters, providing different levels of customization of the information is a desirable goal. Our system allows the automatic generation of visualizations given the semantics of the data, and the static or pre-specified visualization by creating an interface language. We address information visualization taking into consideration the Web, where the presentation of the retrieved information is a challenge. ^ We provide a model to narrow the gap between the user's way of expressing queries and database manipulation languages (SQL) without changing the system itself thus improving the query specification process. We develop a Web interface model that is integrated with the HTML language to create a powerful language that facilitates the construction of Web-based database reports. ^ As opposed to other papers, this model offers a new way of exploring databases focusing on providing Web connectivity to databases with minimal or no result buffering, formatting, or extra programming. We describe how to easily connect the database to the Web. In addition, we offer an enhanced way on viewing and exploring the contents of a database, allowing users to customize their views depending on the contents and the structure of the data. Current database front-ends typically attempt to display the database objects in a flat view making it difficult for users to grasp the contents and the structure of their result. Our model narrows the gap between databases and the Web. ^ The overall objective of this research is to construct a model that accesses different databases easily across the net and generates SQL, forms, and reports across all platforms without requiring the developer to code a complex application. This increases the speed of development. In addition, using only the Web browsers, the end-user can retrieve data from databases remotely to make necessary modifications and manipulations of data using the Web formatted forms and reports, independent of the platform, without having to open different applications, or learn to use anything but their Web browser. We introduce a strategic method to generate and construct SQL queries, enabling inexperienced users that are not well exposed to the SQL world to build syntactically and semantically a valid SQL query and to understand the retrieved data. The generated SQL query will be validated against the database schema to ensure harmless and efficient SQL execution. (Abstract shortened by UMI.)^