Evaluation of Demand Response on System Reliability and Cable Aging

Emergency loading implementation brings reliability and flexibility benefits to the operator. However, its application results in higher cable temperature, which may lead to increase of aging risk. Furthermore, demand response (DR) option can clip the customer loads and shift them to a different period. The DR clipping process reduces the loading of the network to avoid cable overheating and reduce its aging risk. The study aims to evaluate the impact of DR in increasing the reliability of the system as well as reducing the aging of the network. The proposed DR is implemented in the cable-based transmission network, as a complementary of emergency loading, by taking into account the large thermal inertia of the cable. It uses cable temperature elevation as the trigger as an alternative to demand level trigger, which is the traditional approach. The evaluation uses Sequential Monte Carlo Simulation (SMCS) on the IEEE 14 Bus Reliability Test System. The implementation of temperature-based DR reduces the network aging by 3% as well as expected energy not supplied by 34% compared to the emergency loading only

A facile way to produce epoxy nanocomposites having excellent thermal conductivity with low contents of reduced graphene oxide

A well-dispersed phase of exfoliated graphene oxide (GO) nanosheets was initially prepared in water. This was concentrated by centrifugation and was mixed with a liquid epoxy resin. The remaining water was removed by evaporation, leaving a GO dispersion in epoxy resin. A stoichiometric amount of an anhydride curing agent was added to this epoxy-resin mixture containing the GO nanosheets, which was then cured at 90 C for 1 h followed by 160 C for 2 h. A second thermal treatment step of 200 C for 30 min was then undertaken to reduce further the GO in situ in the epoxy nanocomposite. An examination of the morphology of such nanocomposites containing reduced graphene oxide (rGO) revealed that a very good dispersion of rGO was achieved throughout the epoxy polymer. Various thermal and mechanical properties of the epoxy nanocomposites were measured, and the most noteworthy finding was a remarkable increase in the thermal conductivity when relatively very low contents of rGO were present. For example, a value of 0.25 W/mK was measured at 30 C for the nanocomposite with merely 0.06 weight percentage (wt%) of rGO present, which represents an increase of *40% compared with that of the unmodified epoxy polymer. This value represents one of the largest increases in the thermal conductivity per wt% of added rGO yet reported. These observations have been attributed to the excellent dispersion of rGO achieved in these nanocomposites made via this facile production method. The present results show that it is now possible to tune the properties of an epoxy polymer with a simple and viable method of GO addition. A

RNA mutagenesis yields highly diverse mRNA libraries for in vitro protein evolution

BACKGROUND: In protein drug development, in vitro molecular optimization or protein maturation can be used to modify protein properties. One basic approach to protein maturation is the introduction of random DNA mutations into the target gene sequence to produce a library of variants that can be screened for the preferred protein properties. Unfortunately, the capability of this approach has been restricted by deficiencies in the methods currently available for random DNA mutagenesis and library generation. Current DNA based methodologies generally suffer from nucleotide substitution bias that preferentially mutate particular base pairs or show significant bias with respect to transitions or transversions. In this report, we describe a novel RNA-based random mutagenesis strategy that utilizes Qβ replicase to manufacture complex mRNA libraries with a mutational spectrum that is close to the ideal. RESULTS: We show that Qβ replicase generates all possible base substitutions with an equivalent preference for mutating A/T or G/C bases and with no significant bias for transitions over transversions. To demonstrate the high diversity that can be sampled from a Qβ replicase-generated mRNA library, the approach was used to evolve the binding affinity of a single domain V(NAR )shark antibody fragment (12Y-2) against malarial apical membrane antigen-1 (AMA-1) via ribosome display. The binding constant (K(D)) of 12Y-2 was increased by 22-fold following two consecutive but discrete rounds of mutagenesis and selection. The mutagenesis method was also used to alter the substrate specificity of β-lactamase which does not significantly hydrolyse the antibiotic cefotaxime. Two cycles of RNA mutagenesis and selection on increasing concentrations of cefotaxime resulted in mutants with a minimum 10,000-fold increase in resistance, an outcome achieved faster and with fewer overall mutations than in comparable studies using other mutagenesis strategies. CONCLUSION: The RNA based approach outlined here is rapid and simple to perform and generates large, highly diverse populations of proteins, each differing by only one or two amino acids from the parent protein. The practical implications of our results are that suitable improved protein candidates can be recovered from in vitro protein evolution approaches using significantly fewer rounds of mutagenesis and selection, and with little or no collateral damage to the protein or its mRNA

Histone H2A ubiquitination resulting from Brap loss of function connects multiple aging hallmarks and accelerates neurodegeneration

Aging is an intricate process characterized by multiple hallmarks including stem cell exhaustion, genome instability, epigenome alteration, impaired proteostasis, and cellular senescence. Whereas each of these traits is detrimental at the cellular level, it remains unclear how they are interconnected to cause systemic organ deterioration. Here we show that abrogating Brap, a BRCA1-associated protein essential for neurogenesis, results in persistent DNA double-strand breaks and elevation of histone H2A mono- and poly-ubiquitination (H2Aub). These defects extend to cellular senescence and proteasome-mediated histone H2A proteolysis with alterations in cells' proteomic and epigenetic states. Brap deletion in the mouse brain causes neuroinflammation, impaired proteostasis, accelerated neurodegeneration, and substantially shortened the lifespan. We further show the elevation of H2Aub also occurs in human brain tissues with Alzheimer's disease. These data together suggest that chromatin aberrations mediated by H2Aub may act as a nexus of multiple aging hallmarks and promote tissue-wide degeneration

Antisense oligonucleotide therapy for KCNT1 encephalopathy

Published online: 22 November 2022Developmental and epileptic encephalopathies (DEE) are characterized by pharmacoresistant seizures with concomitant intellectual disability. Epilepsy of infancy with migrating focal seizures (EIMFS) is one of the most severe of these syndromes. De novo variants in ion channels, including gain-of-function variants in KCNT1, have been found to play a major role in the etiology of EIMFS. Here, we test a potential precision therapeutic approach in KCNT1-associated DEE using a gene silencing antisense oligonucleotide (ASO) approach. We generated a mouse model carrying the KCNT1 p.P924L pathogenic variant; only the homozygous animals presented with the frequent, debilitating seizures and developmental compromise that are seen in patients. After a single intracerebroventricular bolus injection of a Kcnt1 gapmer ASO in symptomatic mice at postnatal day 40, seizure frequency was significantly reduced, behavioral abnormalities improved, and overall survival was extended compared to mice treated with a control ASO (non-hybridizing sequence). ASO administration at neonatal age was also well-tolerated and effective in controlling seizures and extending the lifespan of treated animals. The data presented here provide proof of concept for ASO-based gene silencing as a promising therapeutic approach in KCNT1-associated epilepsies.Lisseth Estefania Burbano, Melody Li, Nikola Jancovski, Paymaan Jafar-Nejad, Kay Richards, Alicia Sedo, Armand Soriano, Ben Rollo, Linghan Jia, Elena V. Gazina, Sandra Piltz, Fatwa Adikusuma, Paul Q. Thomas, Helen Kopsidas, Frank Rigo, Christopher A. Reid, Snezana Maljevic, Steven Petro

Renal involvement in mitochondrial cytopathies

Mitochondrial cytopathies constitute a group of rare diseases that are characterized by their frequent multisystemic involvement, extreme variability of phenotype and complex genetics. In children, renal involvement is frequent and probably underestimated. The most frequent renal symptom is a tubular defect that, in most severe forms, corresponds to a complete De Toni-Debré-Fanconi syndrome. Incomplete proximal tubular defects and other tubular diseases have also been reported. In rare cases, patients present with chronic tubulo-interstitial nephritis or cystic renal diseases. Finally, a group of patients develop primarily a glomerular disease. These patients correspond to sporadic case reports or can be classified into two major defects, namely 3243 A>G tRNALEU mutations and coenzyme Q10 biosynthesis defects. The latter group is particularly important because it represents the only treatable renal mitochondrial defect. In this Educational Review, the principal characteristics of these diseases and the main diagnostic approaches are summarized

Brine recovery from hypersaline wastewaters from table olive processing by combination of biological treatment and membrane technologies

[EN] The fermentation brines from table olive processing (FTOP) are hypersaline effluents (conductivities higher than 75 mS·cm-1) with high organic matter concentrations (COD around 10 g·L-1), which also include phenolic compounds (between 700 and 1500 mg TY·L-1). In this work, an integrated process for the FTOP reuse as brine in the table olive processing has been evaluated. This integrated process consisted of a biological treatment followed by a membrane system, which included ultrafiltration (UF) plus nanofiltration (NF). The biological treatment was carried out by 6 L laboratory sequencing batch reactor (SBR). UF and NF were performed in laboratory plants for flat membranes of 0.0125 and 0.0072 m2, respectively. Each stream generated during the FTOP treatment (SBR effluent, and UF and NF permeates) were evaluated. The SBR eliminated around 80% of COD and 71% of total phenols concentration. In the final NF permeate the COD concentration was lower than 125 mg·L-1; while the turbidity, colour and phenolic compounds, were completely removed.The authors of this work thank the financial support of CDTI (Centre for Development Technological Industrial) depending on the Spanish Ministry of Science and Innovation.Ferrer-Polonio, E.; Carbonell Alcaina, C.; Mendoza Roca, JA.; Iborra Clar, A.; Alvarez Blanco, S.; Bes-Piá, M.; Pastor Alcañiz, L. (2017). Brine recovery from hypersaline wastewaters from table olive processing by combination of biological treatment and membrane technologies. Journal of Cleaner Production. 142:1377-1386. doi:10.1016/j.jclepro.2016.11.169S1377138614

Network Models of TEM β-Lactamase Mutations Coevolving under Antibiotic Selection Show Modular Structure and Anticipate Evolutionary Trajectories

Understanding how novel functions evolve (genetic adaptation) is a critical goal of evolutionary biology. Among asexual organisms, genetic adaptation involves multiple mutations that frequently interact in a non-linear fashion (epistasis). Non-linear interactions pose a formidable challenge for the computational prediction of mutation effects. Here we use the recent evolution of β-lactamase under antibiotic selection as a model for genetic adaptation. We build a network of coevolving residues (possible functional interactions), in which nodes are mutant residue positions and links represent two positions found mutated together in the same sequence. Most often these pairs occur in the setting of more complex mutants. Focusing on extended-spectrum resistant sequences, we use network-theoretical tools to identify triple mutant trajectories of likely special significance for adaptation. We extrapolate evolutionary paths (n = 3) that increase resistance and that are longer than the units used to build the network (n = 2). These paths consist of a limited number of residue positions and are enriched for known triple mutant combinations that increase cefotaxime resistance. We find that the pairs of residues used to build the network frequently decrease resistance compared to their corresponding singlets. This is a surprising result, given that their coevolution suggests a selective advantage. Thus, β-lactamase adaptation is highly epistatic. Our method can identify triplets that increase resistance despite the underlying rugged fitness landscape and has the unique ability to make predictions by placing each mutant residue position in its functional context. Our approach requires only sequence information, sufficient genetic diversity, and discrete selective pressures. Thus, it can be used to analyze recent evolutionary events, where coevolution analysis methods that use phylogeny or statistical coupling are not possible. Improving our ability to assess evolutionary trajectories will help predict the evolution of clinically relevant genes and aid in protein design

Voice interactive personalized security (VoIPSEC) protocol: Fortify internet telephony by providing end-to-end security through inbound key exchange and biometric verification

Secure end-to-end information exchange is a constant challenge in electronic communications. Novel security architectures and approaches are proposed constantly, to be followed by announcements of sophisticated attack methods that compromise them, while people suspect others, even more sophisticated attack methods never see the daylight. In the present work we propose a novel method for secure end-to-end communication based on biometric evidence to ensure security and integrity of the information exchanged. The traditional approach for securing the communication between two peers is through the use of secret key encryption combined with a public key approach for exchanging the common secret key to be used by the end peers. The public key part of the communication is based on a trusted authority for providing the public keys, a service provided through a Public Key Infrastructure (PKI). Public key infrastructures are vulnerable to man in the middle attacks, among other approaches that compromise their integrity. There has been a lot of work for providing robust PKI infrastructures, the proposed solutions are fairly demanding on network resources, hence public key solutions are not the security approach of choice in several applications that require light weight solutions. Here we propose an approach for providing secure end-to-end communications in environments where it is possible to have biometric based authentication, exploiting the nature of the application; voice communication being the typical example that we use as our paradigm for describing the method. During the establishment of the communication session, the end-peers exchange a challenge/signature token, the integrity of which is confirmed vocally when the voice communication initiates. The security of the method relies on the inability to mechanically impersonate an individual both because of the biometric user specific attributes of the human voice and video as well as the user customized profile of the exchanged information. The method is appropriate for ensuring the security of an encrypted phone conversation, guaranteeing the integrity of the session key exchanged in the beginning of the conversation. It requires minimal resources from the user handsets and no additional support from the network, so it is inherently scalable and readily deployable as it only needs an appropriately enhanced secure handset. ©2006 IEEE