Positive Contrast Imaging of SPIO Nanoparticles

It is advantageous to achieve positive contrast images instead of negative contrast images in superparamagnetic iron-oxide (SPIO) nanoparticles-based MR imaging in order to distinguish the signal surrounding SPIO nanoparticles from the dark signal due to local field inhomogeneity and the artifacts due to tissue interface and background noise, eliminate the inherent defects in the traditional MRI such as partial-volume effects and large void volume for reliable visualization, and increase contrast-to-noise ratio. Many methods generating positive signal with SPIO nanoparticles have been developed in the last decade. This paper provides an overview of current visualization methods and states their advantages and disadvantages. In practice, these techniques have been widely applied to cell labeling and disease diagnosis and monitoring. However, there is still a need for an ideal method to achieve both accuracy and sensitivity

Cost/Benefit Assessment of a Smart Distribution System With Intelligent Electric Vehicle Charging

In the near future, with more distributed generators connected and new demands arising from the electrification of heat and transport in the distribution networks, infrastructure will become ever more stressed. However, building costly new circuits to accommodate generation and demand growth is time-consuming and environmentally unfriendly. Therefore, active network management (ANM) has been promoted in many countries, aiming to relieve network pressure. Previous research in ANM was focused on distribution areas with significant renewable penetration, where ANM reduced network pressure through significantly enhanced generation curtailment strategies rather than adopting traditional asset investment. This paper proposes the use of electric vehicles (EVs) as responsive demand to complement network stress relief that was purely based on generation curtailment. It is achieved by allowing EVs to absorb excessive renewable generation when they cause network pressure, and it thus can provide additional measures to generation curtailment strategies. The approach is illustrated on a practical extra-high voltage distribution system. The analyses clearly demonstrate the combined management of demand and generation is superior to previous sole generation management. The combined management strategy can achieve 7.9% improvement in utilization of renewable energy, and subsequently increase the net investment profit by £566 k

Bi-allelic pathogenic variants in TRMT1 disrupt tRNA modification and induce a neurodevelopmental disorder

Neurodevelopmental disorder; tRNA modification; ZebrafishTrastorno del neurodesarrollo; Modificación de ARNt; Pez cebraTrastorn del neurodesenvolupament; Modificació de tRNA; Peix zebraThe post-transcriptional modification of tRNAs plays a crucial role in tRNA structure and function. Pathogenic variants in tRNA-modification enzymes have been implicated in a wide range of human neurodevelopmental and neurological disorders. However, the molecular basis for many of these disorders remains unknown. Here, we describe a comprehensive cohort of 43 individuals from 31 unrelated families with bi-allelic variants in tRNA methyltransferase 1 (TRMT1). These individuals present with a neurodevelopmental disorder universally characterized by developmental delay and intellectual disability, accompanied by variable behavioral abnormalities, epilepsy, and facial dysmorphism. The identified variants include ultra-rare TRMT1 variants, comprising missense and predicted loss-of-function variants, which segregate with the observed clinical pathology. Our findings reveal that several variants lead to mis-splicing and a consequent loss of TRMT1 protein accumulation. Moreover, cells derived from individuals harboring TRMT1 variants exhibit a deficiency in tRNA modifications catalyzed by TRMT1. Molecular analysis reveals distinct regions of TRMT1 required for tRNA-modification activity and binding. Notably, depletion of Trmt1 protein in zebrafish is sufficient to induce developmental and behavioral phenotypes along with gene-expression changes associated with disrupted cell cycle, immune response, and neurodegenerative disorders. Altogether, these findings demonstrate that loss of TRMT1-catalyzed tRNA modifications leads to intellectual disability and provides insight into the molecular underpinnings of tRNA-modification deficiency caused by pathogenic TRMT1 variants.The authors thank the affected individuals and their families for their support of this study. One of the authors of this publication (Z.T.) is a member of the European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability, ERN-ITHACA (EU Framework Partnership Agreement ID: 3HP-HP-FPA ERN-01-2016/739516). B.V. is a member of the European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability (ERN-ITHACA) (EU Framework Partnership Agreement ID: 3HP-HP-FPA ERN-01-2016/739516). The research in this paper was supported by NIH GM141038 to D.F. Studies performed in the lab of G.K.V. was funded by NIH/ORIP R24OD034438. The clinic-genetic research was funded in part by the Wellcome Trust (WT093205MA and WT104033AIA). This study was funded by the Medical Research Council (MR/S01165X/1, MR/S005021/1, and G0601943), The National Institute for Health Research University College London Hospitals Biomedical Research Centre, Rosetrees Trust, Ataxia UK, Multiple System Atrophy Trust, Brain Research United Kingdom, Sparks Great Ormond Street Hospital Charity, Muscular Dystrophy United Kingdom (MDUK), Muscular Dystrophy Association (MDA USA), and the King Baudouin Foundation. S.E. and H.H. were supported by an MRC strategic award to establish an International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD) MR/S005021/1. B.V. was supported by the Deutsche Forschungsgemeinschaft (DFG) DFG VO 2138/7-1 grant 469177153. J.S. is supported by Cancer Research UK and University College London. A.F. and S.C. were supported by Health & Care Research Wales, Epilepsy Research UK, and Swansea University PhD funding

Multi-Objective Optimization for Customer Flexibility Management to Mitigate Consecutive Days of Power Supply Shortages

Extreme weather such as heatwaves increases the probability of power system supply shortages, thus necessitating enhanced customer flexibility in instances of limited generation-side resources. This paper proposes an optimization model for managing customer flexibility to tackle multiple consecutive days of power supply shortages. Firstly, it constructs a customer flexibility management framework, considering power supply shortages under extreme heatwave conditions. Then, a multi-objective optimization is built for the customer flexibility management center to minimize the customer flexibility management costs and impacts on industrial customers' production. In this model, the impact index and customer uncertainty updating methods are proposed for managing customer flexibility over consecutive days based on exponential smoothing and Bayesian inference methods. A combined Tchebycheff decomposition and the analytic hierarchy process (AHP)-entropy weight method is constructed to tackle the impact of subjective and objective factors on decision-making. Finally, industrial customers in a city of Zhejiang province, China are used for case studies and the result shows that the proposed model can help customer flexibility management centers reduce and delay the power supply shortages during consecutive days of heatwaves.</p

Cost/Benefit Assessment of a Smart Distribution System With Intelligent Electric Vehicle Charging

In the near future, with more distributed generators connected and new demands arising from the electrification of heat and transport in the distribution networks, infrastructure will become ever more stressed. However, building costly new circuits to accommodate generation and demand growth is time-consuming and environmentally unfriendly. Therefore, active network management (ANM) has been promoted in many countries, aiming to relieve network pressure. Previous research in ANM was focused on distribution areas with significant renewable penetration, where ANM reduced network pressure through significantly enhanced generation curtailment strategies rather than adopting traditional asset investment. This paper proposes the use of electric vehicles (EVs) as responsive demand to complement network stress relief that was purely based on generation curtailment. It is achieved by allowing EVs to absorb excessive renewable generation when they cause network pressure, and it thus can provide additional measures to generation curtailment strategies. The approach is illustrated on a practical extra-high voltage distribution system. The analyses clearly demonstrate the combined management of demand and generation is superior to previous sole generation management. The combined management strategy can achieve 7.9% improvement in utilization of renewable energy, and subsequently increase the net investment profit by £566 k

PARK16 rs708730 Polymorphism Decreases Parkinson’s Disease Risk in European Ancestry Population: A Meta-analysis

Parkinson’s disease (PD) is a complex fatal chronic neurodegenerative disease most common in elderly people. The early genome-wide association studies (GWAS) found that the minor allele variant of PARK16 rs708730 polymorphism is a significant protective factor for PD in Caucasian populations. However, these results cannot be repeated by the following studies in Caucasian populations and other populations. We considered that the inconsistency of the findings may be caused by the small-scale samples or the heterogeneity among different populations. Therefore, in this study, we synthesized the previous related GWAS studies through three authoritative sources, and used the large-scale samples (10,645 PD cases and 30,499 controls) to reevaluate the association between rs708730 polymorphism and PD. The results showed that there is no association between them in Asian ancestry population. While, in European ancestry population, we found that the minor allele variant (G) of rs708730 polymorphism is significantly associated with a decreased risk of PD. Collectively, our findings further verified the association of rs708730 with PD and show its genetic heterogeneity among different populations, which can help to develop a better understanding of the PD’s pathogenesis

Preparation and characterization of PLA ultrasound contrast agents by combining an ultrasound method and a Shirasu Porous Glass (SPG) membrane emulsification technique

The ultrasound contrast agent based on a poly lactic acid (PLA) was prepared by combining an ultrasound method and a Shirasu Porous Glass (SPG) membrane emulsification technique. An aqueous phase containing ammonium bicarbonate was used as the internal water phase (WO, and PLA and Span 80 were dissolved in a solvent of dichloromethane (DCM), which was used as the oil phase (0). These two solutions were probe sonicated to form a W(1)/O primary emulstion. The primary emulsion was permeated through the uniform pores (1.1 mu m) of an SPG membrane into the external water phase (W(2)) by the pressure of nitrogen gas to form the uiniform W(1)/O/W(2) droplets. After DCM was evaporated, the hardened PLA microcapsules were further formulated into a lyophilized powder containing decafluorobutane gas. SEM image demonstrated that the PLA microcapsules were sphere-shaped and internally hollow with an average diameter ranging from 1.99 to 3.58 mu m. In vitro, the PLA contrast agents showed high acoustic enhancement properties, the enhancement increased nonlinearly with dose, and the minimal loss (less than 5 dB) of signal was observed over 20 min of analysis at 37 degrees C, the maximum acoustic enhancement was 45 dB, which significantly higher (p<0.01) compared to a value of 28 dB for those prepared by a conventional solvent evaporation method. In conclusion, the hollow PLA microcapsules prepared by the novel method have the characteristics desirable for an intravenously administered ultrasound contrast agents

Multifunctional Ag@Fe(2)O(3) yolk-shell nanoparticles for simultaneous capture, kill, and removal of pathogen

We combined silver and iron oxide nanoparticles to make unique Ag@Fe(2)O(3) yolk-shell multifunctional nanoparticles by the Kirkendall effect. After the surface functionalization using glucose, the Ag@Fe(2)O(3)-Glu conjugates exhibited both high capture efficiency of bacteria and potent antibacterial activity. The Ag@Fe(2)O(3) yolk-shell nanostructures may offer a unique multifunctional platform for simultaneous rapid detection and capture of bacteria and safe detoxification treatment.National Science Foundation of China[21021061, 81000662]; Fundamental Research Funds for the Central Universities[2010121012]; Program for New Century Excellent Talents in University[NCET-10-0709