scholarly journals Targeting the Water Network in Cyclin G‐Associated Kinase (GAK) with 4‐Anilino‐quin(az)oline Inhibitors

ChemMedChem ◽  
2020 ◽  
Vol 15 (13) ◽  
pp. 1200-1215 ◽  
Author(s):  
Christopher R. M. Asquith ◽  
Graham J. Tizzard ◽  
James M. Bennett ◽  
Carrow I. Wells ◽  
Jonathan M. Elkins ◽  
...  
Keyword(s):  
Water Network ◽  
Cyclin G

scholarly journals Targeting the water network in cyclin G associated kinase (GAK) with 4-anilino-quin(az)oline inhibitors

2020 ◽  
Author(s):  
Christopher R. M. Asquith ◽  
Graham J. Tizzard ◽  
James M. Bennett ◽  
Carrow I. Wells ◽  
Jonathan M. Elkins ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Great Promise ◽  
Target Engagement ◽  
Inhibitor Design ◽  
Water Network ◽  
Atp Binding Site ◽  
Cellular Target ◽  
Cyclin G ◽  
Design And Testing ◽  
Targeted Library

AbstractWater networks within kinase inhibitor design and more widely within drug discovery are generally poorly understood. The successful targeting of these networks prospectively has great promise for all facets of inhibitor design, including potency and selectivity on target. Here we describe the design and testing of a targeted library of 4-anilinoquinolines for use as inhibitors of cyclin G associated kinase (GAK). The GAK cellular target engagement assays, ATP binding site modelling and extensive water mapping provide a clear route to access potent inhibitors for GAK and beyond.

An Advanced Software to Manage a Smart Water Network with Innovative Metrics and Tools Based on Social Network Theory

10.29007/gvnz ◽  
2018 ◽  
Author(s):  
Armando Di Nardo ◽  
Michele Di Natale ◽  
Anna Di Mauro ◽  
Eva Martínez Díaz ◽  
Jose Antonio Blázquez Garcia ◽  
...  
Keyword(s):  
Social Network ◽  
Network Theory ◽  
Water Distribution ◽  
Distribution Networks ◽  
Social Network Theory ◽  
Geographical Information ◽  
Water Network ◽  
Time Data ◽  
Water Losses ◽  
Operational Conditions

The recent development and applications of social network theory in many fields of engineering (electricity, gas, transport, water, etc.) allows both the understanding of networks and to improve their management. Social network theory coupled to the availability of real time data and big data analysis techniques can change drastically the traditional approaches to manage civil networks. Recently, some authors are working to apply this novel approach, based on social network theory, on the water distribution networks using: a) graph partitioning algorithms to define optimal district meter areas both for water losses identification and for water network protection, b) innovative topological, energy and hydraulic indices to analyze performance; and c) GIS (Geographical Information System) to provide a more effective display of results and to improve network behavior in specific operational conditions. In this paper, a novel release 3.5 of SWANP software, that implements all these features, was tested on a real large water network in Alcalá de Henares, Spain.

SIMULATION AND CONTROL OF FLOODS IN A WATER NETWORK. CASE STUDY OF JIJIA RIVER CATCHMENT

2017 ◽  
Vol 16 (3) ◽  
pp. 587-595
Author(s):  
Vasile Mircea Cristea ◽  
Ph.m Thai Hoa ◽  
Mihai Mogos-Kirner ◽  
Csavdari Alexandra ◽  
Paul Serban Agachi
Keyword(s):  
Water Network ◽  
River Catchment ◽  
Simulation And Control ◽  
And Control

Tendencias del cambio climático en la Demarcación Hidrográfica de Manabí

2018 ◽  
Vol 3 (1) ◽  
pp. 1
Author(s):  
Campos Cedeño Antonio Fermín ◽  
Mendoza Álava Junior Orlando
Keyword(s):  
El Niño ◽  
El Nino ◽  
Technical Information ◽  
Temporal Distribution ◽  
Temporal Analysis ◽  
Botanical Garden ◽  
Monthly Precipitation ◽  
Water Network ◽  
Monthly Distribution ◽  
Index Terms

Abstract— The Manabí Hydrographic Demarcation (DHM) is characterized as the only one that does not receive input from Andes Mountains, therefore, its water network is fed exclusively by the rainfall that occurs in the rainy season and that the warm current of El Niño plays a fundamental role in its production. In order to have technical information, important for the planning, control and development of the water resources of the DHM, in this research is made a temporal analysis of the monthly precipitation for 55 years, period 1963-2017. The National Institute of Hydrology and Meteorology of Ecuador (INAMHI) in station M005, located in the Botanical Garden of the Technical University of Manabí (Universidad Técnica de Manabí) in Portoviejo, obtained these records. An analysis is made of the monthly and annual patterns, establishing that the El Niño events that occurred in 1983, 1997 and 1998, have set guidelines for the change in rainwater production at the intensity and temporal distribution levels, increasing the months of drought, while the levels of rainfall increase, concentrating in fewer months, basically in February and March. This is a situation that increases the water deficit especially when there is not enough infrastructure of hydraulic works for the storage and regulation of runoff.   Index Terms— Hydrology, rainfall, monthly distribution, annually distribution, climate change, El Niño phenomenon

Sectorisation of looped water networks with electromagnetic water meters

2014 ◽  
Vol 9 (2) ◽  
pp. 150-157
Author(s):  
Koral Wojciech
Keyword(s):  
Water Balance ◽  
Water Networks ◽  
Water Network ◽  
Automatic Meter Reading ◽  
Dead End ◽  
Water Meters ◽  
The Town

This paper describes the sectorisation of a water network, as operated by the water and sewage utility (PWiK Gliwice, Poland) with electromagnetic water-meters (battery powered). This solution allows supply of District Metered Areas (DMA) by a few points without ‘dead-end’ pipework and shows that the main problems of the Utility are small, hidden leaks. Additionally the paper describes a water balance for the town of Pyskowice (part of the Gliwice water network) where all water meters are read by radio (automatic meter reading – AMR).

scholarly journals A Hybrid Methodology to Minimize Freshwater Consumption during Shrimp Shell Waste Valorization Combining Multi-Contaminant Pinch Analysis and Superstructure Optimization

Polymers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1887
Author(s):  
Viviana Quintero ◽  
Arturo Gonzalez-Quiroga ◽  
Angel Darío Gonzalez-Delgado
Keyword(s):  
Process Integration ◽  
Preliminary Design ◽  
Water Network ◽  
Hybrid Strategy ◽  
Shrimp Shell ◽  
Optimal Value ◽  
Shell Waste ◽  
Programming Techniques ◽  
Shrimp Shell Waste ◽  
Freshwater Consumption

The conservation and proper management of natural resources constitute one of the main objectives of the 2030 Agenda for Sustainable Development designed by the Member States of the United Nations. In this work, a hybrid strategy based on process integration is proposed to minimize freshwater consumption while reusing wastewater. As a novelty, the strategy included a heuristic approach for identifying the minimum consumption of freshwater with a preliminary design of the water network, considering the concept of reuse and multiple pollutants. Then, mathematical programming techniques were applied to evaluate the possibilities of regeneration of the source streams through the inclusion of intercept units and establish the optimal design of the network. This strategy was used in the shrimp shell waste process to obtain chitosan, where a minimum freshwater consumption of 277 t/h was identified, with a reuse strategy and an optimal value of US $5.5 million for the design of the water network.

scholarly journals Characterization of microbial antifreeze protein with intermediate activity suggests that a bound-water network is essential for hyperactivity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
N. M.-Mofiz Uddin Khan ◽  
Tatsuya Arai ◽  
Sakae Tsuda ◽  
Hidemasa Kondo
Keyword(s):  
Crystal Structure ◽  
Basal Plane ◽  
Molecular Mechanisms ◽  
Bound Water ◽  
Hydrophobic Hydration ◽  
Water Network ◽  
Molecular Scaffold ◽  
Intermediate Activity ◽  
Mold Fungus ◽  
Antifreeze Activity

AbstractAntifreeze proteins (AFPs) inhibit ice growth by adsorbing onto specific ice planes. Microbial AFPs show diverse antifreeze activity and ice plane specificity, while sharing a common molecular scaffold. To probe the molecular mechanisms responsible for AFP activity, we here characterized the antifreeze activity and crystal structure of TisAFP7 from the snow mold fungus Typhula ishikariensis. TisAFP7 exhibited intermediate activity, with the ability to bind the basal plane, compared with a hyperactive isoform TisAFP8 and a moderately active isoform TisAFP6. Analysis of the TisAFP7 crystal structure revealed a bound-water network arranged in a zigzag pattern on the surface of the protein’s ice-binding site (IBS). While the three AFP isoforms shared the water network pattern, the network on TisAFP7 IBS was not extensive, which was likely related to its intermediate activity. Analysis of the TisAFP7 crystal structure also revealed the presence of additional water molecules that form a ring-like network surrounding the hydrophobic side chain of a crucial IBS phenylalanine, which might be responsible for the increased adsorption of AFP molecule onto the basal plane. Based on these observations, we propose that the extended water network and hydrophobic hydration at IBS together determine the TisAFP activity.

Infrastructures as colonial beachheads: The Central Arizona Project and the taking of Navajo resources

2021 ◽  
pp. 026377582199153
Author(s):  
Andrew Curley
Keyword(s):  
Colorado River ◽  
Water Network ◽  
Navajo Nation ◽  
Political Factors ◽  
Indian Water ◽  
Central Arizona Project ◽  
Indigenous Lands ◽  
Archival Documents ◽  
Central Arizona ◽  
Colorado River Water

Colonial difference is a story of national infrastructures. To understand how colonialism works across Indigenous lands, we need to appreciate the physical, legal, and political factors involved in the building and expanding of national infrastructures in different historical contexts; infrastructures that arrive in some places while denied in others. Using archival documents, this article accounts for the colonial politics necessary to bring Colorado River water into Phoenix and Tucson. It highlights how the following moments worked to enlarge Arizona’s population and power while denying Diné water claims: the 1922 Colorado Compact, Arizona’s 1960s campaign for the Central Arizona Project, and recent Indian water settlements between Arizona and Navajo Nation. The infrastructures that emerged from these events formed a coal–energy–water nexus reliant on Navajo coal while constructing Arizona’s water network. In sum, these projects served as colonial beachheads—temporal encroachments on Indigenous lands and livelihoods that augment material and political difference over time and exacerbate inequalities.

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