214 research outputs found
Control of human VDAC-2 scaffold dynamics by interfacial tryptophans is position specific
AbstractMembrane proteins employ specific distribution patterns of amino acids in their tertiary structure for adaptation to their unique bilayer environment. The solvent-bilayer interface, in particular, displays the characteristic ‘aromatic belt’ that defines the transmembrane region of the protein, and satisfies the amphipathic interfacial environment. Tryptophan—the key residue of this aromatic belt—is known to influence the folding efficiency and stability of a large number of well-studied α-helical and β-barrel membrane proteins. Here, we have used functional and biophysical techniques coupled with simulations, to decipher the contribution of strategically placed four intrinsic tryptophans of the human outer mitochondrial membrane protein, voltage-dependent anion channel isoform-2 (VDAC-2). We show that tryptophans help in maintaining the structural and functional integrity of folded hVDAC-2 barrel in micellar environments. The voltage gating characteristics of hVDAC-2 are affected upon mutation of tryptophans at positions 75, 86 and 221. We observe that Trp-160 and Trp-221 play a crucial role in the folding pathway of the barrel, and once folded, Trp-221 helps stabilize the folded protein in concert with Trp-75 and Trp-160. We further demonstrate that substituting Trp-86 with phenylalanine leads to the formation of stable barrel. We find that the region comprising strand β4 (Trp-86) and β10-14 (Trp-160 and Trp-221) display slower and faster folding kinetics, respectively, providing insight into a possible directional folding of hVDAC-2 from the C-terminus to N-terminus. Our results show that residue selection in a protein during evolution is a balancing compromise between optimum stability, function, and regulating protein turnover inside the cell
DandeBot - An Autonomous Weeding Solution for Residential Lawns
DandeBot – An Autonomous Weeding Solution for Residential Lawns
Author: Nishanth Rajkumar
This thesis presents the development and validation of DandeBot, an autonomous robotic system designed for comprehensive residential lawn maintenance. The robot addresses the need for efficient, eco-conscious, and low maintenance lawn care through a fully electric platform powered by an AI-driven software stack. Emphasizing safety, adaptability, and ease of use, the hardware was developed using CAD and Design for Manufacturing (DFM) principles, resulting in a modular and robust design. The integrated software stack combines localization, mapping, and path planning using odometry, visual odometry, and IMU data fusion to navigate dynamic outdoor environments. Task-specific algorithms were developed and validated for autonomous navigation, weed detection, and obstacle avoidance. Key hardware innovations include a modular gripper system for weed removal and adaptable attachments for multiple lawn care tasks. Field trials confirmed the robot’s capability to perform with high precision and reliability in varied lawn conditions, significantly reducing the need for human intervention. This work contributes to the growing field of service robotics by demonstrating how intelligent systems can automate routine household maintenance. The thesis concludes by outlining future research directions, including system scalability, enhanced multi-tasking capabilities, and integration with smart home networks
‐2: Mitochondrial outer membrane regulator masquerading as a channel?
The voltage-dependent anion channels (VDACs) are the workforce of mitochondrial transport and as such are required for cellular metabolism. The elaborate interplay between mitochondria and the apoptotic pathway supports a role for VDACs as a major regulator of cell death. Although VDAC-1 has an established role in apoptosis and cell homeostasis, the role of VDAC-2 has been controversial. In humans, VDAC-2 is best known for its anti-apoptotic properties. In this Viewpoint, we associate the various functional studies on VDAC-2 with structural reports, to decode its unique behavior. The well-structured N-terminus, compact barrel form, differences in the loop regions, specific transmembrane segments and the abundance of thiols in VDAC-2 enable this isoform to perform a different subset of regulatory functions, establish anti-apoptotic features and contribute to gametogenesis. VDAC-2 structural features that demarcate it from VDAC-1 suggest that this particular isoform is better suited for regulating reactive oxygen species, steroidogenesis and mitochondria-associated endoplasmic reticulum membrane regulatory pathways, with ion transport forming a secondary role. A better understanding of the unique structural features of the VDAC family will aid in the design of inhibitors that could alleviate irregularities in VDAC-controlled pathways
Exploring Stability and Accuracy Limits of Distributed Real-Time Power System Simulations via System-of-Systems Cosimulation
Electro-Magnetic Transients (EMT) is the most accurate, but computationally expensive method of analyzing power system phenomena. Thereby, interconnecting several real-time simulators can unlock scalability and system coverage, but leads to a number of new challenges, mainly in time synchronization, numerical stability, and accuracy quantification. This study presents such a co-simulation, based on Digital Real-Time Simulator (DRTS), connected via Aurora 8B/10B protocol. Such a setup allows to analyze complex and hybrid System-of-Systems (SoS) whose resulting numerical phenomena and artifacts have been poorly investigated and understood so far. We experimentally investigate the impact of IEEE 1588 Precision Time Protocol (PTP) synchronization assessing both time and frequency domains. The analysis of the experimental results is encouraging and show that numerical stability can be maintained even with complex system setups. Growing shares of inverter-based renewable power generation require larger and interconnected EMT system studies. This work helps to understand the phenomena connected to such DRTS advanced co-simulation setups
A THERAPEUTIC JOURNEY OF MIXED LIGAND COMPLEXES CONTAINING 1,10-PHENANTROLINE DERIVATIVES: A REVIEW
Schiff bases have been exposed to reveal a wide range of biological activities, including antifungal, antibacterial, antimalarial, antiproliferative, anti-inflammatory, antiviral, and antipyretic properties. Mixed ligand complexes can be a synthetic challenge to tune the properties of the transition metal complexes. The review of this paper covers updated information on the most active mixed ligand metal complexes of 1,10-phenantroline derivatives that have been reported to prove considerable pharmacological actions such as, antifungal, antibacterial, antitumor, antimalarial, antiviral and other biological activities. In the present study, we summarized the biological aspects, chemistry and applications of some important mixed ligand complexes. This review is balancing to earlier reviews and aims to review the work reported on various biological activities of mixed ligand complexes bearing 1,10-phenantroline derivatives from year 2000 to the beginning of 2016
Semantic Question Classification Datasets
This is the datasets used in the following paper:Can Taxonomy Help? Improving Semantic Question Matching using Question TaxonomyPaper: http://aclweb.org/anthology/C18-1042If you use the dataset please cite the following paper:@InProceedings{C18-1042,
author = "Gupta, Deepak
and Pujari, Rajkumar
and Ekbal, Asif
and Bhattacharyya, Pushpak
and Maitra, Anutosh
and Jain, Tom
and Sengupta, Shubhashis",
title = "Can Taxonomy Help? Improving Semantic Question Matching using Question Taxonomy",
booktitle = "Proceedings of the 27th International Conference on Computational Linguistics",
year = "2018",
publisher = "Association for Computational Linguistics",
pages = "499--513",
location = "Santa Fe, New Mexico, USA",
url = "http://aclweb.org/anthology/C18-1042"
}
</div
Stability and Accuracy Analysis of a Real-time Co-simulation Infrastructure
Co-simulation techniques are gaining popularity amongst the power system research community to analyse future scalable Smart Grid solutions. However, complications such as multiple communication protocols, uncertainty in latencies are holding-up the widespread usage of these techniques for power system analysis. These issues are even further exacerbated when applied to Digital Real-Time Simulations (DRTS) with strict real-time constraints for Power Hardware-In-the-Loop (PHIL) tests. In this paper, we thoroughly test and demonstrate an innovative co-simulation infrastructure that allows to interconnect different DRTS through the Aurora 8B/10B protocol to reduce the effects of communication latency and respect real-time constraints. The Ideal Transformer Method Interface Algorithm (ITM IA), commonly used in PHIL applications, is used to interface the DRTS. Finally, we present time-domain and frequency-domain accuracy analyses on the obtained experimental results to demonstrate the potential of the proposed infrastructure.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Intelligent Electrical Power Grid
Improvement of cost estimating internal practice.
This thesis is concerned with understanding the internal costing practices employed
by commercial and engineering disciplines of cost estimating for generating
estimates at the conceptual design stage of complex hardware products. It examines
whether there is a formal structure in the interaction between the two groups that
can be represented within a model. The aim is to develop a framework that will
formalise and improve the communication of commercial and engineering
disciplines in cost estimating.
A literature review examines the role of different costing techniques and the
information requirements for generating cost estimates. The review identifies that
there is a lack of research in the information requirements for cost estimating of
specific manufacturing industries, and that the interaction of commercial and
engineering disciplines of cost estimating at conceptual design stage is hindered by
the different focuses of these groups.
By conducting a survey study the author identifies the internal practice in
cost estimating for the automotive industry. The survey establishesth at in order to
improve the internal practice it is essential to establish a data infrastructure that
fortnalises and enables the reuse of the cost estimates and improves the interaction
between the two groups. The author identifies a common cost estimating process
for the automotive industry. This study establishes the required data and
information elements and information sources that need to be collected in order to
have reliable data infrastructure. Using a case study approach, the author also
establishes that it is essential to analyse the product functions in such a way that
will enable the development of a detailed cost estimating model at the conceptual
design stage, which will improve interaction between the commercial and
engineering groups. The function-based cost estimating process becomes the focus
of detailed studies using experts from the automotive industry. This results in a
generic framework that provides a formalised structure to represent functional
requirements in the form of a detailed cost estimating model.
The thesis concludes that product functions need to be captured and
analysedd uring the conceptuald evelopmento f a product and be associatedto cost
estimates. The developed results provide both groups of cost estimating a
structured, consistent approach to developing cost estimates at the conceptual
design stage. The data infrastructure and the function-based cost estimating
framework is validated through case studies and expert evaluation. The approach
contributes towards improvement of the internal cost estimating practice with the
automotive industry
Influence of protein-micelle ratios and cysteine residues on the kinetic stability and unfolding rates of human mitochondrial VDAC-2.
Delineating the kinetic and thermodynamic factors which contribute to the stability of transmembrane β-barrels is critical to gain an in-depth understanding of membrane protein behavior. Human mitochondrial voltage-dependent anion channel isoform 2 (hVDAC-2), one of the key anti-apoptotic eukaryotic β-barrel proteins, is of paramount importance, owing to its indispensable role in cell survival. We demonstrate here that the stability of hVDAC-2 bears a strong kinetic contribution that is dependent on the absolute micellar concentration used for barrel folding. The refolding efficiency and ensuing stability is sensitive to the lipid-to-protein (LPR) ratio, and displays a non-linear relationship, with both low and high micellar amounts being detrimental to hVDAC-2 structure. Unfolding and aggregation process are sequential events and show strong temperature dependence. We demonstrate that an optimal lipid-to-protein ratio of 2600∶1 - 13,000∶1 offers the highest protection against thermal denaturation. Activation energies derived only for lower LPRs are ∼17 kcal mol(-1) for full-length hVDAC-2 and ∼23 kcal mol(-1) for the Cys-less mutant, suggesting that the nine cysteine residues of hVDAC-2 impart additional malleability to the barrel scaffold. Our studies reveal that cysteine residues play a key role in the kinetic stability of the protein, determine barrel rigidity and thereby give rise to strong micellar association of hVDAC-2. Non-linearity of the Arrhenius plot at high LPRs coupled with observation of protein aggregation upon thermal denaturation indicates that contributions from both kinetic and thermodynamic components stabilize the 19-stranded β-barrel. Lipid-protein interaction and the linked kinetic contribution to free energy of the folded protein are together expected to play a key role in hVDAC-2 recycling and the functional switch at the onset of apoptosis
Development of an impact assessment framework for lean manufacturing within SMEs
The main aim of the research work presented in this thesis, is the development of a
novel framework with the capability of assessing the impact of implementing lean
manufacturing within small-to-medium sized manufacturing firms (SMEs). By assessing
the impact of lean implementation, SMEs can make informed decisions on the viability
of lean adoption at the conceptual implementation stage. Companies are also able
determine their status in terms of lean manufacturing affordability.
Thus, in order to achieve the above-stated aim, the following were the main set research
objectives; (1) identifying the key drivers for implementing lean manufacturing within
SMEs, (2) investigating the operational activities of SMEs in order to understand their
manufacturing issues, (3) exploring the current level of lean manufacturing usage within
SMEs so as to categorise users based on their levels of involvement, (4) identifying
factors that determine the assessment of lean manufacturing, (5) developing an impact
assessment framework for justifying lean manufacturing within SMEs, (6) developing a
knowledge based advisory system and (7) validating the impact assessment framework
and the developed knowledge based advisory system through real-life case studies,
workshops, and expert opinions.
A combination of research methodology approaches have been employed in this
research study. This comprises literature review, observation of companies' practices
and personal interview. The data collection process involved ten SMEs that provided
consistent information throughout the research project life. Additionally, visitations to
three large size manufacturing firms were also conducted. Hence, the framework and
system development process passed through several stages. Firstly, the data were
collected from companies who had successfully implemented lean manufacturing within
their premise. The second development stage included the analysis and validation of the
dataset through company practitioners. An impact assessment framework was thus developed with the aid of regression analysis as a predictive model. However, it was
realised that there were few correlations between the dataset generated and analysis. The
reasons for this were unclear.
,a
knowledge based advisory system was adopted to
conceptualise, enhance the robustness of the impact assessment framework and address
the problem of the imprecise data in the impact assessment process.
Three major factors of impact assessment were considered in the framework and the
system development process, namely relative cost of lean implementation, a company
lean readiness status and the level of value-added to be achieved (impact/benefits).
Three knowledge based advisory sub-systems that consisted of the abovementioned
factors were built. Results obtained from them were then fed into the final system. The
three sub-systems were validated with the original set of data from companies. This
enabled the assignment of a number of input variables whose membership functions
aided the definition of the fuzzy expert system language (linguistic variables) used. The
final system yielded heuristic rules that enable the postulation of scenarios of lean
implementation. Results were sought and tested on a number of firms based within the
UK, for the purposes validation. These also included expert opinions both in academic
and industrial settings.
A major contribution of the developed system is its ability to aid decision-making
processes for lean implementation at the early implementation stage. The visualisation
facility of the developed system is also useful in enabling potential lean users to make
forecasts on the relative cost of lean projects upfront, anticipate lean benefits, and realise
one' degree of lean readiness
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