scholarly journals A comparison of mechanistic signaling pathway activity analysis methods

2018 ◽  
Vol 20 (5) ◽  
pp. 1655-1668 ◽  
Author(s):  
Alicia Amadoz ◽  
Marta R Hidalgo ◽  
Cankut Çubuk ◽  
José Carbonell-Caballero ◽  
Joaquín Dopazo

Abstract Understanding the aspects of cell functionality that account for disease mechanisms or drug modes of action is a main challenge for precision medicine. Classical gene-based approaches ignore the modular nature of most human traits, whereas conventional pathway enrichment approaches produce only illustrative results of limited practical utility. Recently, a family of new methods has emerged that change the focus from the whole pathways to the definition of elementary subpathways within them that have any mechanistic significance and to the study of their activities. Thus, mechanistic pathway activity (MPA) methods constitute a new paradigm that allows recoding poorly informative genomic measurements into cell activity quantitative values and relate them to phenotypes. Here we provide a review on the MPA methods available and explain their contribution to systems medicine approaches for addressing challenges in the diagnostic and treatment of complex diseases.

2016 ◽  
Vol 10 (2) ◽  
pp. 136-148
Author(s):  
Renata Marques de Oliveira ◽  
Antonia Regina Ferreira Furegato

The objective of this study was to investigate elements of the personal and psychiatric history, as well as the challenges related to motherhood, of a young schizophrenic female, through person-centered therapeutic interaction. The investigation had an exploratory scope, undertaken in a teaching hospital and data were collected during nondirective interaction on the part of the nurse with a young schizophrenic woman who had been treated in the institution for 10 years. Thematic analysis of the content was undertaken, with emphasis on the nuclei of meaning, identification of the themes and definition of the categories. The patient, called L. in this study, was 30 years old, had a two-year-old child and was three months pregnant when data were collected. Her trajectory was characterized by doubts, fears and uncertainties. The episodes of hospitalization, the coexistence with other patients, and the medications promoted insight into the symptoms, and acceptance of the diagnosis. The main challenge was experiencing pregnancy and the puerperium concomitantly with the psychiatric treatment. The interpersonal relationship established evidenced that, the young woman felling understood and that her needs were attended, overcame several difficulties she had reported and felt fulfilled and integrated into her social environment.


Author(s):  
Mirjana Maksimović

Nowhere do the technology advancements bring improvements than in the healthcare sector, constantly creating new healthcare applications and systems which completely revolutionize the healthcare domain. The appearance of Internet of Things (IoT) based healthcare systems has immensely improved quality and delivery of care, and significantly reduced the costs. At the same time, these systems generate the enormous amount of health-associated data which has to be properly gathered, analyzed and shared. The smart devices, as the components of IoT-driven healthcare systems, are not able to deal with IoT-produced data, neither data posting to the Cloud is the appropriate solution. To overcome smart devices’ and Cloud’s limitations the new paradigm, known as Fog computing, has appeared, where an additional layer processes the data and sends the results to the Cloud. Despite numerous benefits Fog computing brings into IoT-based environments, the privacy and security issues remain the main challenge for its implementation. The reasons for integrating the IoT-based healthcare system and Fog computing, benefits and challenges, as well as the proposition of simple low-cost system are presented in this paper.


2019 ◽  
Vol 278 (3) ◽  
pp. 113
Author(s):  
Francisco Sérgio Maia Alves

<p>The new paradigm of decision based on art. 20 of the LINDB: analysis of the text according to the theories of Richard Posner and Neil MacCormick</p><p> </p><p>O presente trabalho visa analisar o art. 20 da Lei de Introdução às Normas do Direito Brasileiro (LINDB), introduzido pela Lei nº 13.655/2018. Para tanto, será mostrado como os valores jurídicos foram excluídos e novamente reintroduzidos na prática jurídica e como essa reintrodução gerou preocupações quanto ao aumento da discricionariedade da aplicação do direito. O artigo apresentará as teorias pragmática e consequencialista, segundo a doutrina de dois de seus principais expoentes, Richard Posner e Neil MacCormick. No afã de cumprir o objetivo central do artigo, serão delimitados os conceitos de valores jurídicos abstratos e consequências práticas da decisão, no contexto do art. 20 da LINDB, e, por fim, definido o espaço de aplicação do dispositivo.</p><p> </p><p>This work aims to analyze art. 20 of the Law of Introduction to the Rules of Brazilian Law (LINDB), or Law No. 13.655/2018. To do so, it will be shown how legal values were excluded and reintroduced in legal practice and how this reintroduction raised concerns regarding the increase of discretion in the application of the law. The article will present pragmatic and consequentialist theories, in line with the doctrine of two of its main exponents, Richard Posner and Neil MacCormick. In order to meet the key objective of the article, the concepts of abstract legal values and practical consequences of the decision will be described in the context of art. 20 of the LINDB, concluding with a definition of the area in which the law is applied.</p>


2021 ◽  
Author(s):  
Olena Ovcharuk ◽  

The main approaches to the methodology of staff incentive and engagement are considered in the article. The research aim is to develop theoretical and methodological provisions, methodological approaches to the formation, functioning and development of a staff incentive scheme. Today, economics has developed several contradictory approaches to the definition of a category “staff incentive scheme”, as a consequence of ambiguous understanding of such categories as “motive” and “stimulant”, “engagement” and “incentive”. The issue of the relation between these concepts has remained controversial. In management practice, these categories are not differentiated, they are considered rather as synonymous concepts. The author has summarized the views of economists on the essence of the “incentive” and “engagement” concepts. It has been determined that, most scientists proceed from the fact that engagement is a broader concept than incentive. The article examines the engagement process from the standpoint of the stimulant impact on the motive formation. Staff incentive in an organization is not only a process but also a system, therefore, defining the technological component of the methodology, the author considered it as a system and process at the same time. The article describes the structure of a staff incentive scheme in different types of social and labor relations. As a result of studying the genesis of social and labor relations and the conceptual fundamentals of management and engagement, society development and the scientific and technological progress, the author found that development of a theoretical and methodological approach to staff incentive is efficient and meets the requirements of a new paradigm of socio-economic systems. A theoretical and methodological approach to staff incentive has been offered. This approach differs in the concepts of incentive as a system and process in the formation and support of which the object of management together with the subject is involved. The worldview aspect of the methodology was formed as a result of the development of mechanistic, humanistic, socially-oriented and participative approaches to human resources management. The cognitive component of the methodology is shown in the development of theories which reflect this evolution: classical management theories, the concept of human relations, the concept of human resources, the concept of socially responsible and ethical management.


2019 ◽  
Vol 98 (7) ◽  
pp. 761-765 ◽  
Author(s):  
N. I. Prokhorov ◽  
V. I. Dontsov ◽  
Vyacheslav N. Krutko ◽  
T. M. Khodykina

The widespread formation of unfavorable environmental, the swiftness of modern life with large information and psycho-emotional loads and extremely natural and climatic cataclysms, as well as harmful addictions and wrong way of life of modern human, lead to the development of stress and disruption of the mechanisms of adaptation of the human body and its accelerated wear. This stimulates the development of research on the creation of new methods of integrated assessment of health and quantitative assessment of the aging processes of the body systems and the whole body, as well as the possibilities of new methods of risk assessment of climatic and environmentally related pathological and age-related diseases. The aim of the work was to consider the methodology of quantitative assessment of individual health and the rate of aging of the human body on the basis of the system index of Biological age (BA); description of its essence and structure, requirements for tests - biomarkers of aging used as the index of BA, definition of possibilities and scope of application of the BA method in modern practice of Biomedicine. The use of modern methods of scientific analysis - a systematic approach to the analysis of the processes of human aging and determine its quantitative side - the value of BA, allows a reasonable approach to the choice of the number of BM, to take into account their information content and precision, and the cost of diagnostics and availability for different users, to take into account the specific objectives of the researcher. The use of the index-partial BA allows individual approaching the choice of biomarkers and create personalized panels for the definition of BA programs for the prevention of aging in personalized preventive medicine. The complexity of the content and calculation of indices of BA requires automation and the use of methods of modern computer science and computer calculations and programs. For this purpose, we have created special computer software for diagnosing aging by calculating the BA indices with the possibility of choosing BM and automatic calculation of indicators and conclusions.


2021 ◽  
Author(s):  
Xavier Rubio-Campillo ◽  
Eduard Ble ◽  
Àngels Pujol ◽  
Roger Sala ◽  
Robert Tamba

Landscape plays a vital role in the development of military campaigns through the definition of geostrategic landmarks that structure the control of the territory, the imposition of constraints to the movement of armies, and the identification of positions that facilitate defensive tactics against aggressors. These factors are linked to the study of past spatial mobility which is typically performed using Least-Cost Path analysis (LCP). LCP identifies the optimal route that connects any two given points based on minimizing the accumulated cost based on a friction surface map, thus allowing archaeologists to identify the most efficient pathways across a territory. The main challenge of LCP analysis for archaeological regions is that optimal pathways are not well suited to define general mobility patterns within highly uncertain scenarios. Connectivity modelling based on Circuit Theory (CT) is an alternative approach to the study of mobility. CT does not generate a single path like LCP does; it captures the connectivity of an entire region identifying not only optimal paths, but also bottlenecks, dead-ends and any other spatial feature that may impact movement.We present here a framework to study landscapes of conflict using connectivity modelling; the framework combines CT, visibility analysis and statistical hypothesis testing to understand the reasons behind the assault and destruction of Puig Ciutat (NE Iberian Peninsula) during Julius Caesar's civil war. Results suggest that the site exerted decisive control over a highly connected area linking two possible logistical bases (Emporion and Massalia) to the armies fighting at Ilerda (49 BC).


2020 ◽  
Author(s):  
Alberto Scoma

AbstractMicrobial preference for elevated hydrostatic pressure (HP) is a recognized key feature of environmental and industrial processes. HP effects on macromolecules and, consequently, cell functionality has been accurately described in the last decades. While there is little debate about the importance of HP in shaping microbial life, a systematic definition of microbial preference for increased HP is missing. The lack of a consensus about ‘true’ piezophiles, and ‘low’ or ‘high’ HP levels, has deleterious repercussions on microbiology and biotechnology. As certain levels are considered ‘low’ they are not applied to assess microbial activity. Most microorganisms collected in deep waters or sediments have not been tested (nor isolated) using the corresponding HP at which they were captured. Microbial response to HP is notoriously dependent on other environmental parameters, most notably temperature, but also on availability of nutrients, growth substrate, pH and salinity. This implies that countless isolates retrieved from ambient pressure conditions may very well require increased HP to grow optimally, as already demonstrated in both Archaea and Bacteria.In the present study, I collected the data from described piezophilic isolates and used the fundamental correlation existing between HP and temperature, as first suggested in seminal works by Yayanos, to update the definition of piezophiles. Thanks to the numerous new piezophilic isolates available since such seminal studies, the present analysis brings forward updated definitions which concern 1) the actual beginning of the piezosphere, the area in the deep sea where piezophiles thrive; 2) the HP thresholds which should be considered low, medium and high HP, and their implications for experimental design in Microbiology; and 3) the nature of obligate piezophiles and their location in the deep sea.


2011 ◽  
Vol 49 (1) ◽  
pp. 150-150

Jules H. van Binsbergen of Northwestern University, Stanford University, and NBER reviews “Anticipating Correlations: A New Paradigm for Risk Management” by Robert Engle. The EconLit Abstract of the reviewed work begins, “Presents a collection of new methods for estimating and forecasting correlations for large systems of assets. Discusses correlation economics; correlations in theory; models for correlation; dynamic conditional correlation; dynamic conditional correlation performance; the MacGyver method; generalize….”


Author(s):  
B. R. Thatch ◽  
A. Myklebust

Abstract Creation of input specifications for synthesis or analysis of spatial mechanisms can be a significant problem. A graphics preprocessor which interactively assists in the definition of spatial mechanism problems is described. New methods of depth cucing and six DOF data entry are presented. To achieve graphics device-independence, the proposed graphics standard PHIGS (Programmer’s Hierarchical Interactive Graphics System) is used. Examples of application are presented including generation of input commands for Integrated Mechanisms Program (IMP) and generation of input for spatial mechanism synthesis routines.


Author(s):  
Frédérique de Vignemont ◽  
Andrea Serino ◽  
Hong Yu Wong ◽  
Alessandro Farnè

Research in cognitive neuroscience indicates that we process the space surrounding our body in a specific way, both for protecting our body from immediate danger and for interacting with the environment. This research has direct implications for philosophical issues as diverse as self-location, sensorimotor theories of perception, and affective perception. This chapter briefly describes the overall directions that some of these discussions might take. But, beforehand, it is important to fully grasp what the notion of peripersonal space involves. One of the most difficult questions that the field has had to face these past 30 years is to define peripersonal space. Although it bears some relations to the social notion of personal space, to the sensorimotor notion of reaching space and to the spatial notion of egocentric space, there is something unique about peripersonal space and the special way we represent it. One of the main challenges is thus to offer a satisfactory definition of peripersonal space that is specific enough to account for its peculiar spatial, multisensory, plastic, and motor properties. Emphasis can be put on perception or on action, but also on impact prediction or defence preparation. However, each new definition brings with it new methods to experimentally investigate peripersonal space. There is then the risk of losing the unity of the notion of peripersonal space within this multiplicity of conceptions and methods. This chapter offers an overview of the key notions in the field, the way they have been operationalized, and the questions they leave open.


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