Aromatase inhibitors and antiepileptic drugs: a computational systems biology analysis

<p>Abstract</p> <p>Background</p> <p>The present study compares antiepileptic drugs and aromatase (CYP19) inhibitors for chemical and structural similarity. Human aromatase is well known as an important pharmacological target in anti-breast cancer therapy, but recent research demonstrates its role in epileptic seizures, as well. The current antiepileptic treatment methods cause severe side effects that endanger patient health and often preclude continued use. As a result, less toxic and more tolerable antiepileptic drugs (AEDs) are needed, especially since every individual responds differently to given treatment options.</p> <p>Methods</p> <p>Through a pharmacophore search, this study shows that a model previously designed to search for new classes of aromatase inhibitors is able to identify antiepileptic drugs from the set of drugs approved by the Food and Drug Administration. Chemical and structural similarity analyses were performed using five potent AIs, and these studies returned a set of AEDs that the model identifies as hits.</p> <p>Results</p> <p>The pharmacophore model returned 73% (19 out of 26) of the drugs used specifically to treat epilepsy and approximately 82% (51 out of 62) of the compounds with anticonvulsant properties. Therefore, this study supports the possibility of identifying AEDs with a pharmacophore model that had originally been designed to identify new classes of aromatase inhibitors. Potential candidates for anticonvulsant therapy identified in this manner are also reported. Additionally, the chemical and structural similarity between antiepileptic compounds and aromatase inhibitors is proved using similarity analyses.</p> <p>Conclusions</p> <p>This study demonstrates that a pharmacophore search using a model based on aromatase inhibition and the enzyme's structural features can be used to screen for new candidates for antiepileptic therapy. In fact, potent aromatase inhibitors and current antiepileptic compounds display significant - over 70% - chemical and structural similarity, and the similarity analyses performed propose a number of antiepileptic compounds with high potential for aromatase inhibition.</p

INTERCULTURAL COMMUNICATION, THE BASIS OF THE ORGANIZATIONAL CULTURE

Communication expresses the connections between the purposes and the instruments used by a transmitter of a message. Inside the cultural grounds generated by a society – defining for the system of values of a community, it may as well facilitate, complicate or even erase any connection between individual and language. In a binary system determined by what is acquired and what is innate, the cultural factor reveals its multiple meanings, and besides any stream of appearances the two initiate a reciprocal determination. As culture is a guarantee of the functionality of a behavior, the success of an organization also depends upon the communication between the employees but as well of the connection between managerial decisions and their practice. Thus the cultural differences between the employees have to be taken into consideration, and mostly they have to be reduced so as not to transform into conflicts. Still, at times, it is these differences proper which make for the value of the idiom like „unity in diversity” and also define intercultural communication. For such a context like the business one the impact of the professional culture on a more general one is highly decisive. The assimilation of the organizational culture is accomplished by acknowledging and promoting the landmarks of the national culture while its development finds its own landmarks in notions like: the vocation, the effort and the imagination of the ones involved in initiating and maintaining a business. Consequently, the present analysis attempts to express the correspondence between the mental map of a population (its bias for certain values) and the predominant pattern of the organizational culture of that particular country.Communication, Culture, Intercultural Communication, Image of the Organization, Organizational Culture

THE IMPACT OF GLOBALIZATION ON REGULATIONS AND ACCOUNTING SYSTEMS. DIMENSIONING AND QUANTIFICATION.

In this study we concentrate our efforts on the consequences that the existence and manifestation of globalization have on various domains of human activity. The impact of globalization will be analyzed from the perspective of the cause-effect relationship, with a special emphasis on the consequences of the phenomenon. A special part of our scientific demarche is reserved to the accounting sphere. We try to create a new dimension on the basement of relations between globalization and accounting systems. Globalization represents a new dimension of our world. The accounting domain is today into real connections with phenomenon of globalization. In this context, our main objectives are represented by the research demarche to create a model of quantification the impact of globalization on regulations and accounting systems. We believe that such a model of quantification could be real and its contributions to scientific development will be considerable.Globalization, International Accounting, Impact, Quantification

INTERCULTURAL COMMUNICATION, THE BASIS OF THE ORGANIZATIONAL CULTURE

Communication expresses the connections between the purposes and the instruments used by a transmitter of a message. Inside the cultural grounds generated by a society – defining for the system of values of a community, it may as well facilitate, complicate or even erase any connection between individual and language. In a binary system determined by what is acquired and what is innate, the cultural factor reveals its multiple meanings, and besides any stream of appearances the two initiate a reciprocal determination. As culture is a guarantee of the functionality of a behavior, the success of an organization also depends upon the communication between the employees but as well of the connection between managerial decisions and their practice. Thus the cultural differences between the employees have to be taken into consideration, and mostly they have to be reduced so as not to transform into conflicts. Still, at times, it is these differences proper which make for the value of the idiom like „unity in diversity” and also define intercultural communication. For such a context like the business one the impact of the professional culture on a more general one is highly decisive. The assimilation of the organizational culture is accomplished by acknowledging and promoting the landmarks of the national culture while its development finds its own landmarks in notions like: the vocation, the effort and the imagination of the ones involved in initiating and maintaining a business. Consequently, the present analysis attempts to express the correspondence between the mental map of a population (its bias for certain values) and the predominant pattern of the organizational culture of that particular country

THE IMPACT OF GLOBALIZATION ON REGULATIONS AND ACCOUNTING SYSTEMS. DIMENSIONING AND QUANTIFICATION.

In this study we concentrate our efforts on the consequences that the existence and manifestation of globalization have on various domains of human activity. The impact of globalization will be analyzed from the perspective of the cause-effect relationship, with a special emphasis on the consequences of the phenomenon. A special part of our scientific demarche is reserved to the accounting sphere. We try to create a new dimension on the basement of relations between globalization and accounting systems. Globalization represents a new dimension of our world. The accounting domain is today into real connections with phenomenon of globalization. In this context, our main objectives are represented by the research demarche to create a model of quantification the impact of globalization on regulations and accounting systems. We believe that such a model of quantification could be real and its contributions to scientific development will be considerable

Overview of the technologies used in the fabrication of MEMS/NEMS actuators for space applications

Given the advantages in terms of weight, size and cost and because it can withstand severe shocks and temperature changes, the MEMS/NEMS sensors are widely used in the aerospace domain. This paper presents a brief history of the scientists who made reference to micro and nano technologies for the first time, followed by a synthesis of the leading technologies used in the manufacture of microelectromechanical systems (MEMS) and nanoelectromechanical systems (NEMS) intensively used in aerospace industry. After reviewing the latest technologies used in the manufacture of MEMS/NEMS sensors, the paper continues with predicting the current state regarding the development of NEMS and MEMS, respectively

(St)aging in place: Information and communication technologies for a health-centered agile dwelling unit

As the number of older adults is growing rapidly in the U.S., the need for personalized, innovative, and sustainable Information and Communication Technologies (ICTs) solutions is critical to support individuals' social, emotional, and physical health. Such technology can significantly help older adults' ability to live independently in their homes despite the challenges the aging process may present, referred to as aging or staging in place. In this study, we explored ways to integrate ICTs into Agile Dwelling Units (AgDUs) through affordable, innovative, technology-enabled tools and practices that can be adapted to respond to individual's needs while supporting independent, secure, and engaged healthy living. The technology-enabled and human-centered AgDUs organically transform in response to users' needs. This approach offers a viable solution for older adults at different stages throughout their lifespan to transition into an intimate, technologically-enhanced living environment while allowing for (1) customization to user's needs; (2) cost optimization and maintenance; and (3) accessibility that minimizes gaps in compliance from a provider and user perspectives. Integrating ICTs in AgDUs to support health monitoring and management could reduce forthcoming pressure on the healthcare system and care providers to accommodate the needs of older adults. This approach is described through a collaborative multidisciplinary lens that highlights a partnership between academia, industry experts, and key stakeholders to advance healthy living and extend lifespan through design-build and technology integration. The main goal of this approach is to increase access to health services and optimize healthcare costs

A target-based high throughput screen yields Trypanosoma brucei hexokinase small molecule inhibitors with antiparasitic activity. PLoS Negl Trop. Dis

Abstract Background: The parasitic protozoan Trypanosoma brucei utilizes glycolysis exclusively for ATP production during infection of the mammalian host. The first step in this metabolic pathway is mediated by hexokinase (TbHK), an enzyme essential to the parasite that transfers the c-phospho of ATP to a hexose. Here we describe the identification and confirmation of novel small molecule inhibitors of bacterially expressed TbHK1, one of two TbHKs expressed by T. brucei, using a high throughput screening assay