167 research outputs found
LIPIcs, Volume 261, ICALP 2023, Complete Volume
LIPIcs, Volume 261, ICALP 2023, Complete Volum
2019 GREAT Day Program
SUNY Geneseo’s Thirteenth Annual GREAT Day.https://knightscholar.geneseo.edu/program-2007/1013/thumbnail.jp
LIPIcs, Volume 274, ESA 2023, Complete Volume
LIPIcs, Volume 274, ESA 2023, Complete Volum
Chapter 34 - Biocompatibility of nanocellulose: Emerging biomedical applications
Nanocellulose already proved to be a highly relevant material for biomedical
applications, ensued by its outstanding mechanical properties and, more importantly, its biocompatibility. Nevertheless, despite their previous intensive
research, a notable number of emerging applications are still being developed.
Interestingly, this drive is not solely based on the nanocellulose features, but also
heavily dependent on sustainability. The three core nanocelluloses encompass
cellulose nanocrystals (CNCs), cellulose nanofibrils (CNFs), and bacterial nanocellulose (BNC). All these different types of nanocellulose display highly interesting biomedical properties per se, after modification and when used in
composite formulations. Novel applications that use nanocellulose includewell-known areas, namely, wound dressings, implants, indwelling medical
devices, scaffolds, and novel printed scaffolds. Their cytotoxicity and biocompatibility using recent methodologies are thoroughly analyzed to reinforce their
near future applicability. By analyzing the pristine core nanocellulose, none
display cytotoxicity. However, CNF has the highest potential to fail long-term
biocompatibility since it tends to trigger inflammation. On the other hand, neverdried BNC displays a remarkable biocompatibility. Despite this, all nanocelluloses clearly represent a flag bearer of future superior biomaterials, being
elite materials in the urgent replacement of our petrochemical dependence
Unravelling the reaction mechanism of glutamate amidation in Staphylococcus aureus peptidoglycan
MurT-GatD is the bi-enzymatic complex responsible for catalysing the amidation of peptidoglycan in Gram-positive bacteria, ensuring the correct assembly of their cell wall. MurT-GatD is essential in antibiotic resistant human pathogens such as Staphylococcus aureus, Streptococcus pneumoniae and Mycobacterium tuberculosis, and therefore, constitutes a promising target for the development of new antimicrobial agents. Peptidoglycan amidation is achieved through the glutamine amidotransferase activity of the MurT-GatD complex, requiring the presence of glutamine, ATP and magnesium. The main goal of this thesis is to unravel the reaction mechanism of peptidoglycan amidation through an integrative approach that combines structural methods with functional assays, in order to characterize the structure-function relationship of the S. aureus MurT-GatD complex.
The crystal structure of isolated S. aureus GatD was solved at 1.9 Å of resolution (PDB 5N9M) and provided the first structural insights into the MurT-GatD complex. GatD adopts the overall fold of glutaminase proteins and shows the nucleophilic cysteine and the polarizing histidine commonly associated with glutamine hydrolysis. 1H-NMR experiments showed that GatD C94A or H189A abolished the glutaminase activity of the complex. Similarly, GatD R128 also proved to be an essential residue for catalysis, likely by capturing glutamine to the active site.
The crystal structure of S. aureus MurT-GatD was solved at 2.9 Å of resolution (PDB 7Q8E), showing a heterodimer in an extended conformation. GatD adopts the same glutaminase-like fold as in its isolated form, while MurT displays two distinct domains: the central domain containing, a cysteine-rich insertion and the ATP binding site, and the C-terminal domain that interacts with GatD. The overall structure of S. aureus MurT-GatD is very different from S. pneumoniae MurT-GatD, which adopts a compact conformation. The two complexes also adopt different conformations in solution, as observed through Small-Angle X-ray Scattering (SAXS) studies, and showed different in vitro enzymatic activities, suggesting that the extended conformation of S. aureus MurT-GatD is catalytically less competent.
The structural data of MurT-GatD from S. aureus and S. pneumoniae were combined to identify the molecular determinants involved in the glutaminase and amidotransferase active sites of the complex, as well as, in protein-protein interactions. The work carried out in this thesis contributed to the clarification of the reaction mechanism of peptidoglycan amidation, which can be explored for the development of new drugs with antimicrobial activity.MurT-GatD é o complexo bi-enzimático que catalisa a amidação do peptidoglicano em bactérias Gram-positivas, garantindo a correta organização da sua parece celular. MurT-GatD é essencial em bactérias resistentes a antibióticos que são patogénicas a humanos, como Staphylococcus aureus, Streptococcus pneumoniae e Mycobacterium tuberculosis, e, consequentemente constitui um alvo promissor a ter em conta no desenvolvimento de novos agentes antimicrobianos. A amidação do peptidoglicano é realizada pela actividade de glutamina amidotransferase do complexo MurT-GatD, requerendo a presença de glutamina, ATP e magnésio. O principal objectivo desta tese é revelar o mecanismo reaccional da amidação do peptidoglicano através de uma abordagem integrativa que combina métodos estruturais com ensaios funcionais, de modo a caracterizar a relação estrutura-função do complexo MurT-GatD de S. aureus.
A estrutura cristalina da proteína GatD de S. aureus foi resolvida a 1.9 Å de resolução (PDB 5N9M) e forneceu as primeiras evidências estruturais sobre o complexo MurT-GatD. GatD adopta uma organização 3D semelhante a glutaminases, apresentando uma cisteína nucleofílica e uma histidina polarizadora comummente associadas à hidrólise de glutamina. Experiências de 1H-NMR mostraram que os mutantes C94A ou H189A da GatD aboliram a actividade de glutaminase do complexo. De forma similar, R128 da GatD também provou ser um resíduo essencial na catálise, provavelmente por capturar glutamina para o centro activo.
A estrutura cristalina do complexo MurT-GatD de S. aureus foi resolvida a 2.9 Å de resolução (PDB 7Q8E), mostrando um heterodímero numa conformação estendida. A GatD adopta a mesma organização estrutural característica de glutaminases, enquanto a MurT apresenta dois domínios distintos: o domínio central que contém uma inserção rica em cisteínas e o local de ligação ao ATP, e o domínio C-terminal que interage com a GatD. A estrutura global do complexo MurT-GatD de S. aureus é muito diferente do complexo MurT-GatD de S. pneumoniae, tendo em conta que este adopta uma conformação compacta. Os dois complexos também adoptam diferentes conformações em solução, como observado através de estudos de Dispersão de raios X a Baixo Ângulo (SAXS), tendo demonstrado diferentes actividades enzimática in vitro, sugerindo que a conformação estendida de MurT-GatD de S. aureus é cataliticamente menos competente.
Os dados estruturais sobre o complexo MurT-GatD de S. aureus e S. pneumoniae foram combinados para identificar os determinantes moleculares envolvidos nos centros activos de glutaminase e de amidotransferase do complexo, assim como, nas interacções proteína-proteína. O trabalho desta tese teve uma importante contribuição para a elucidação do mecanismo reaccional da amidação do peptidoglicano, o que pode vir a ser explorado no desenvolvimento de novos fármacos com actividade antimicrobiana
LIPIcs, Volume 244, ESA 2022, Complete Volume
LIPIcs, Volume 244, ESA 2022, Complete Volum
Collected Papers (on various scientific topics), Volume XIII
This thirteenth volume of Collected Papers is an eclectic tome of 88 papers in various fields of sciences, such as astronomy, biology, calculus, economics, education and administration, game theory, geometry, graph theory, information fusion, decision making, instantaneous physics, quantum physics, neutrosophic logic and set, non-Euclidean geometry, number theory, paradoxes, philosophy of science, scientific research methods, statistics, and others, structured in 17 chapters (Neutrosophic Theory and Applications; Neutrosophic Algebra; Fuzzy Soft Sets; Neutrosophic Sets; Hypersoft Sets; Neutrosophic Semigroups; Neutrosophic Graphs; Superhypergraphs; Plithogeny; Information Fusion; Statistics; Decision Making; Extenics; Instantaneous Physics; Paradoxism; Mathematica; Miscellanea), comprising 965 pages, published between 2005-2022 in different scientific journals, by the author alone or in collaboration with the following 110 co-authors (alphabetically ordered) from 26 countries: Abduallah Gamal, Sania Afzal, Firoz Ahmad, Muhammad Akram, Sheriful Alam, Ali Hamza, Ali H. M. Al-Obaidi, Madeleine Al-Tahan, Assia Bakali, Atiqe Ur Rahman, Sukanto Bhattacharya, Bilal Hadjadji, Robert N. Boyd, Willem K.M. Brauers, Umit Cali, Youcef Chibani, Victor Christianto, Chunxin Bo, Shyamal Dalapati, Mario Dalcín, Arup Kumar Das, Elham Davneshvar, Bijan Davvaz, Irfan Deli, Muhammet Deveci, Mamouni Dhar, R. Dhavaseelan, Balasubramanian Elavarasan, Sara Farooq, Haipeng Wang, Ugur Halden, Le Hoang Son, Hongnian Yu, Qays Hatem Imran, Mayas Ismail, Saeid Jafari, Jun Ye, Ilanthenral Kandasamy, W.B. Vasantha Kandasamy, Darjan Karabašević, Abdullah Kargın, Vasilios N. Katsikis, Nour Eldeen M. Khalifa, Madad Khan, M. Khoshnevisan, Tapan Kumar Roy, Pinaki Majumdar, Sreepurna Malakar, Masoud Ghods, Minghao Hu, Mingming Chen, Mohamed Abdel-Basset, Mohamed Talea, Mohammad Hamidi, Mohamed Loey, Mihnea Alexandru Moisescu, Muhammad Ihsan, Muhammad Saeed, Muhammad Shabir, Mumtaz Ali, Muzzamal Sitara, Nassim Abbas, Munazza Naz, Giorgio Nordo, Mani Parimala, Ion Pătrașcu, Gabrijela Popović, K. Porselvi, Surapati Pramanik, D. Preethi, Qiang Guo, Riad K. Al-Hamido, Zahra Rostami, Said Broumi, Saima Anis, Muzafer Saračević, Ganeshsree Selvachandran, Selvaraj Ganesan, Shammya Shananda Saha, Marayanagaraj Shanmugapriya, Songtao Shao, Sori Tjandrah Simbolon, Florentin Smarandache, Predrag S. Stanimirović, Dragiša Stanujkić, Raman Sundareswaran, Mehmet Șahin, Ovidiu-Ilie Șandru, Abdulkadir Șengür, Mohamed Talea, Ferhat Taș, Selçuk Topal, Alptekin Ulutaș, Ramalingam Udhayakumar, Yunita Umniyati, J. Vimala, Luige Vlădăreanu, Ştefan Vlăduţescu, Yaman Akbulut, Yanhui Guo, Yong Deng, You He, Young Bae Jun, Wangtao Yuan, Rong Xia, Xiaohong Zhang, Edmundas Kazimieras Zavadskas, Zayen Azzouz Omar, Xiaohong Zhang, Zhirou Ma.
Proceedings of the 22nd Conference on Formal Methods in Computer-Aided Design – FMCAD 2022
The Conference on Formal Methods in Computer-Aided Design (FMCAD) is an annual conference on the theory and applications of formal methods in hardware and system verification. FMCAD provides a leading forum to researchers in academia and industry for presenting and discussing groundbreaking methods, technologies, theoretical results, and tools for reasoning formally about computing systems. FMCAD covers formal aspects of computer-aided system design including verification, specification, synthesis, and testing
Multi-Scale Modeling and Simulation of Cell Signaling and Transport in Renal Collecting Duct Principal Cells
The response of cells to their environment is driven by a variety of proteins and messenger molecules. In eukaryotes, their distribution and location in the cell is regulated by the vesicular transport system. The transport of aquaporin 2 between membrane and storage region is a crucial part of the water reabsorption in renal principal cells, and its malfunction can lead to Diabetes insipidus. To understand the regulation of this system, I aggregated pathways and mechanisms from literature and derived models in a hypothesis-driven approach. Furthermore, I combined the models to a single multi-scale model to gain insight into key regulatory mechanisms of aquaporin 2 recycling. To achieve this, I developed a computational framework for the modeling and simulation of cellular signaling systems. The framework integrates reaction and difusion of biochemical entities on a microscopic scale with mobile vesicles, membranes, and compartments on a cellular level. The simulation uses an adaptive step-width approach that e ciently regulates the agent-based simulation of macroscopic components with the numerical integration of mass action kinetics and grid-based nite diference methods. A reaction network generation algorithm was designed, that, in combination with a highly-modular modeling approach, allows for fast model prototyping. The analysis of the aquaporin 2 model system rationalizes that the compartmentalization of cAMP in renal principal cells is a result of the protein kinase A signalosome and can only occur if speci c cellular components are observed in conjunction. Endocytotic and exocytotic processes are inherently connected and can be regulated by the same protein kinase A signal.:Abstract
1. Introduction
1.1. Eukaryotic Signaling
1.2. Modeling and Simulation of Cellular Processes
1.3. Aquaporin 2 recycling
1.4. Motivation and Aims
1.5. Outline
I. Background
2. Modeling and Simulation of Complex Signaling Pathways
2.1. Multi-scale Modeling
2.1.1. Approaches to Multi-scale Modeling
2.1.2. Reduction of Computational Complexity
2.2. Models of Chemical Reaction Networks
2.2.1. Reactions and Reaction Rates
2.2.2. Numerical Solutions
2.2.3. Reaction Network Generation
2.3. Models of Intracellular Transport
2.3.1. Undirected Transport
2.3.2. Directed Transport
3. Aquaporin 2 Recycling in Renal Principal Cells
3.1. The Physiology of Water Homeostasis
3.2. Molecular Mechanisms of the Vasopressin Response
3.2.1. The Vasopressin Receptor
3.2.2. cAMP Regulation of Protein Kinase A
3.2.3. Endo- and Exocytosis
3.3. Models of Water Transport in Renal Principal Cells
II. Results & Discussion
4. Multi-scale Simulation of Cellular Signaling Pathways
4.1. Scale Separation and Bridging
4.2. Micro-scale Simulation Approach
4.2.1. Difusion and Discretization of the Simulation Space
4.2.2. Reaction Kinetics
4.3. Rule-based Reaction Network Generation
4.3.1. Definition of the Data Model
4.3.2. Design of Rule Based Reactions
4.3.3. Automated Generation of Reaction Networks
4.4. Macro-scale Simulation Approach
4.4.1. Agent-based Simulation of Discrete Entities
4.4.2. Modules for Displacement-based Behavior
4.5. Modularization and Error Estimation
4.5.1. Determination of the Numerical Error
4.5.2. Modularization of Concentration-based Events
4.5.3. Determination of the Displacement-based Error
5. Aquaporin 2 Recycling Model and Simulation
5.1. Model of Allosteric PKA Phosphorylation
5.1.1. Model Design
5.1.2. Simulation Results and Discussion
5.1.3. Conclusions
5.2. cAMP Compartmentalization in the Vesicle Storage Region
5.2.1. Model Design
5.2.2. Simulation Results and Discussion
5.2.3. Conclusions
5.3. Clathrin-mediated Endocytosis
5.3.1. Model Design
5.3.2. Simulation Results and Discussion
5.3.3. Conclusions
5.4. Intracellular Transport and Recycling
5.4.1. Model Design
5.4.2. Simulation Results and Discussion
6. Conclusion
6.1. Modeling and simulation approach
6.2. Insights into the AQP2 recycling model
III. Appendix
A. Code Availability
B. Module Overview
Bibliograph
SpiNNaker - A Spiking Neural Network Architecture
20 years in conception and 15 in construction, the SpiNNaker project has delivered the world’s largest neuromorphic computing platform incorporating over a million ARM mobile phone processors and capable of modelling spiking neural networks of the scale of a mouse brain in biological real time. This machine, hosted at the University of Manchester in the UK, is freely available under the auspices of the EU Flagship Human Brain Project. This book tells the story of the origins of the machine, its development and its deployment, and the immense software development effort that has gone into making it openly available and accessible to researchers and students the world over. It also presents exemplar applications from ‘Talk’, a SpiNNaker-controlled robotic exhibit at the Manchester Art Gallery as part of ‘The Imitation Game’, a set of works commissioned in 2016 in honour of Alan Turing, through to a way to solve hard computing problems using stochastic neural networks. The book concludes with a look to the future, and the SpiNNaker-2 machine which is yet to come
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