Water Distribution Networks (WDNs) are critical infrastructures that ensure a continuous supply of safe water to homes. In the face of challenges, like water scarcity, establishing resilient networks is imperative, especially in regions vulnerable to water crises. This study evaluates the resilience of network designs through graph theory, including its hydraulic feasibility using EPANET software, an aspect often overlooked.
View Article and Find Full Text PDFFor this study, we investigated efficient strategies for the recovery of individual links in power grids governed by the direct current (DC) power flow model, under random link failures. Our primary objective was to explore the efficacy of recovering failed links based solely on topological network metrics. In total, we considered 13 recovery strategies, which encompassed 2 strategies based on link centrality values (link betweenness and link flow betweenness), 8 strategies based on the products of node centrality values at link endpoints (degree, eigenvector, weighted eigenvector, closeness, electrical closeness, weighted electrical closeness, zeta vector, and weighted zeta vector), and 2 heuristic strategies (greedy recovery and two-step greedy recovery), in addition to the random recovery strategy.
View Article and Find Full Text PDFNetwork controllability and its robustness have been widely studied. However, analytical methods to calculate network controllability with respect to node in- and out-degree targeted removals are currently lacking. This paper develops methods, based on generating functions for the in- and out-degree distributions, to approximate the minimum number of driver nodes needed to control directed networks, during node in- and out-degree targeted removals.
View Article and Find Full Text PDFAlthough vaccination is still considered to be the cornerstone of public health care, the increase in vaccination coverage has stagnated for many diseases. Most of these vaccines require two or three doses to be administered across several months or years. Single-injection vaccine formulations are an effective method to overcome the logistical barrier to immunization that is posed by these multiple-injection schedules.
View Article and Find Full Text PDFThe multifunctional human Parkinson's disease protein 7 (PARK7/DJ1) is an attractive therapeutic target due to its link with early-onset Parkinson's disease, upregulation in various cancers, and contribution to chemoresistance. However, only a few compounds have been identified to bind PARK7 due to the lack of a dedicated chemical toolbox. We report the creation of such a toolbox and showcase the application of each of its components.
View Article and Find Full Text PDFHow does the spread of behavior affect consensus-based collective decision-making among animals, humans or swarming robots? In prior research, such propagation of behavior on social networks has been found to exhibit a transition from simple contagion-i.e, based on pairwise interactions-to a complex one-i.e.
View Article and Find Full Text PDFCore-shell microspheres hold great promise as a drug delivery system because they offer several benefits over monolithic microspheres in terms of release kinetics, for instance a reduced initial burst release, the possibility of delayed (pulsatile) release, and the possibility of dual-drug release. Also, the encapsulation efficiency can significantly be improved. Various methods have proven to be successful in producing these core-shell microspheres, both the conventional bulk emulsion solvent evaporation method and methods in which the microspheres are produced drop by drop.
View Article and Find Full Text PDFFor many vaccines, multiple injections are required to confer protective immunity against targeted pathogens. These injections often consist of a primer administration followed by a booster administration of the vaccine a few weeks or months later. A single-injection vaccine formulation that provides for both administrations could greatly improve the convenience and vaccinee's compliance.
View Article and Find Full Text PDFMany reagents have emerged to study the function of specific enzymes On the other hand, target specific reagents are scarce or need improvement, allowing investigations of the function of individual enzymes in their native cellular context. Here we report the development of a target-selective fluorescent small-molecule activity-based DUB probe that is active in live cells and an animal model. The probe labels active ubiquitin carboxy-terminal hydrolase L1 (UCHL1), also known as neuron-specific protein PGP9.
View Article and Find Full Text PDFTransbound Emerg Dis
March 2021
Purpose: Therapies directed to specific molecular targets are still unmet for patients with triple-negative breast cancer (TNBC). Deubiquitinases (DUB) are emerging drug targets. The identification of highly active DUBs in TNBC may lead to novel therapies.
View Article and Find Full Text PDFNetworks are often made up of several layers that exhibit diverse degrees of interdependencies. An interdependent network consists of a set of graphs G that are interconnected through a weighted interconnection matrix B, where the weight of each intergraph link is a non-negative real number p. Various dynamical processes, such as synchronization, cascading failures in power grids, and diffusion processes, are described by the Laplacian matrix Q characterizing the whole system.
View Article and Find Full Text PDFSuccessful immunization often requires a primer, and after a certain lag time, a booster administration of the antigen. To improve the vaccinees' comfort and compliance, a single-injection vaccine formulation with a biphasic pulsatile release would be preferable. Previous work has shown that such a release profile can be obtained with compacts prepared from physical mixtures of various poly(dl-lactic(-co-glycolic) acid) types (Murakami et al.
View Article and Find Full Text PDFAn optimized large scale and highly reproducible route to orthogonally protected γ-thiolysine is reported. Its utility in the synthesis of bifunctional ubiquitin monomers is demonstrated. These ubiquitin synthons are employed in polymerization reactions giving access to synthetic poly-ubiquitin chains of defined linkage.
View Article and Find Full Text PDFDeubiquitinating enzymes (DUBs) catalyze the cleavage of ubiquitin from target proteins. Ubiquitin is post-translationally attached to proteins and serves as an important regulatory signal for key cellular processes. In this study, novel activity-based probes to study DUBs were synthesized that comprise a ubiquitin moiety and a novel disulfide warhead at the C-terminus.
View Article and Find Full Text PDFVarious real-world networks interact with and depend on each other. The design of the interconnection between interacting networks is one of the main challenges to achieve a robust interdependent network. Due to cost considerations, network providers are inclined to interconnect nodes that are geographically close.
View Article and Find Full Text PDFTemozolomide is a chemotherapeutic drug that is mainly used in the treatment of primary glioblastoma multiforme and recurrent high-grade glioma. Here, we report an efficient good manufacturing practice compliant method for the synthesis of [3-N-(11) C-methyl]temozolomide from 3-N-hydroxymethyl temozolomide that cleaves off formaldehyde in situ and becomes activated towards alkylation with [(11) C]methyl iodide. The labelling method was developed for an on-going patient study in which the predictive value of [3-N-(11) C-methyl]temozolomide and positron emission tomography on the outcome of temozolomide treatment is being investigated.
View Article and Find Full Text PDFIntroduction: To analyse the impact of both epilepsy and pharmacological modulation of P-glycoprotein on brain uptake and kinetics of positron emission tomography (PET) radiotracers [(11)C]quinidine and [(11)C]laniquidar.
Methods: Metabolism and brain kinetics of both [(11)C]quinidine and [(11)C]laniquidar were assessed in naive rats, electrode-implanted control rats, and rats with spontaneous recurrent seizures. The latter group was further classified according to their response to the antiepileptic drug phenobarbital into "responders" and "non-responders".
Multivalency is an important phenomenon in protein-carbohydrate interactions. In order to evaluate glycodendrimers as multivalent inhibitors of carbohydrate binding proteins, we displayed them on a microarray surface. Valencies were varied from 1 to 8, and corrections were made for the valencies so that all surfaces contained the same amount of the sugar ligand.
View Article and Find Full Text PDFA galabiose disaccharide building block was synthesized by an efficient pectinase cleavage of polygalacturonic acid and subsequent chemical functional group transformations. Besides the disaccharide, the corresponding trisaccharide was also obtained and modified. The compounds were subsequently conjugated to dendrimers with up to eight end groups using 'click' chemistry.
View Article and Find Full Text PDFIn 2004 a law was introduced in The Netherlands, which gives offspring conceived by semen or oocyte donation the right to know the identity of the donor. The law also regulates the provision of other information concerning the donor to the offspring, their parents or their general practitioner. With the introduction of this law, a choice has been made in which the wish of offspring prevails above others involved.
View Article and Find Full Text PDFThe occurrence of DNA breaks in human sperm is of concern to genetic safety in artificial reproduction techniques. Here, we have explored the neutral comet assay (NCA) for evaluating the frequency of spermatozoa with double strand (ds) DNA breaks in normospermic donors. The NCA results into DNA tail formation by fibre extension and by the separation of DNA fragments.
View Article and Find Full Text PDFAn assumption in case-control studies is that forces of selection are the same for cases and controls. This may not be true for studies of male infertility among infertility clients. Earlier reproductive outcomes may introduce modification of risk behavior or differential referral.
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