To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE), underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate masks and respirators exposed to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus.
The 2 arms of the study included (1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment and (2) PPE treatment with MBL for 5 cycles of decontamination to determine maintenance of PPE performance.
MBL treatment was used to inactivate coronaviruses on 3 N95 filtering facepiece respirator (FFR) and 2 medical mask models. We inoculated FFR and medical mask materials with 3 coronaviruses, including SARS-CoV-2, and we treated them with 10 µM MB and exposed them to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5 cycles of decontamination using multiple US and international test methods, and the process was compared with the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method.
Overall, MBL robustly and consistently inactivated all 3 coronaviruses with 99.8% to >99.9% virus inactivation across all FFRs and medical masks tested. FFR and medical mask integrity was maintained after 5 cycles of MBL treatment, whereas 1 FFR model failed after 5 cycles of VHP+O3.
MBL treatment decontaminated respirators and masks by inactivating 3 tested coronaviruses without compromising integrity through 5 cycles of decontamination. MBL decontamination is effective, is low cost, and does not require specialized equipment, making it applicable in low- to high-resource settings.
ABSTRACT IMPACT: By assessing function of mutant (patient-specific) tp53 in zebrafish embryonal rhabdomyosarcoma will inform clinicians of the severity of mutant tp53 alleles. OBJECTIVES/GOALS: This study aims to define loss- and gain-of-function TP53 mutations by comparing effects in tp53-null and wild-type tumors. In addition, it aims to generate a rapid in vivo analysis platform to assign function to patient specific TP53 mutations in the clinic METHODS/STUDY POPULATION: To define tp53 function in ERMS pathogenesis, we previously generated a new tp53-null mutant (tp53-/-) in zebrafish by deleting the entire tp53 genomic locus using TALEN mutagenesis. tp53-/- zebrafish spontaneously develop a spectrum of tumors including sarcomas, leukemia and germ cell tumors (Ignatius…Baxi et. al., eLife) reminiscent of tumors observed in Trp53-null mice. Using the tp53-/- mutants to generate kRASG12D-induced ERMS, we discovered that tp53 is a potent repressor of metastases but rather surprisingly had no effect on self-renewal (Ignatius…Baxi et. al., eLife). Here, using tp53-/- zebrafish, we assessed effects of wild-type and mutant (patient specific) tp53 on tumor initiation, proliferation and apoptosis. RESULTS/ANTICIPATED RESULTS: ERMS tumor initiation in the tp53-/- background is observed in > 97% of animals whereas only <40% of wild-type animals develop ERMS. Additionally, tp53 is a potent suppressor of ERMS proliferation and its effect on apoptosis is minor. Next, we expressed either WT zebrafish or human TP53 in tp53-/- animals along with kRASG12D and both genes suppressed tumor initiation and growth. We co-expressed TP53C176F (found in two ERMS patients) and TP53P153del (identified in a patient with osteosarcoma in our clinic) in zebrafish ERMS, and find that the TP53C176F allele significantly suppressed tumor initiation with effects predominantly on enhanced apoptosis. However, the TP53P153del allele initiated tumors at similar frequency compared to tp53-/- animals but increased the initiation of tumors in the head musculature. DISCUSSION/SIGNIFICANCE OF FINDINGS: Different TP53 alleles identified in patient tumors have very different effects on tumorigenesis in vivo and can respond differently to potentially therapeutic compounds. Thus, the type of precision modeling demonstrated here promises to help further define patient-specific TP53 biology and improve clinical strategies in the future.
The retirement systems in many developed countries have been increasingly moving from defined benefit towards defined contribution system. In defined contribution systems, financial and longevity risks are shifted from pension providers to retirees. In this paper, we use a probabilistic approach to analyse the uncertainty associated with superannuation accumulation and decumulation. We apply an economic scenario generator called the Simulation of Uncertainty for Pension Analysis (SUPA) model to project uncertain future financial and economic variables. This multi-factor stochastic investment model, based on the Monte Carlo method, allows us to obtain the probability distribution of possible outcomes regarding the superannuation accumulation and decumulation phases, such as relevant percentiles. We present two examples to demonstrate the implementation of the SUPA model for the uncertainties during both phases under the current superannuation and Age Pension policy, and test two superannuation policy reforms suggested by the Grattan Institute.
Electrochemical energy-storage systems such as supercapacitors and lithium-ion batteries require complex intertwined networks that provide fast transport pathways for ions and electrons without interfering with their energy density. Self-assembly of nanomaterials into hierarchical structures offers exciting possibilities to create such pathways. This article summarizes recent research achievements in self-assembled zero-dimensional, one-dimensional, and two-dimensional nanomaterials, ordered pore structure materials, and the interfaces between these. We analyze how self-assembly strategies can create storage architectures that improve device performance toward higher energy densities, longevity, rate capability, and device safety. At the end, the remaining challenges of scalable low-cost manufacturing and future opportunities such as self-healing are discussed.
The Eating Assessment in Toddlers FFQ (EAT FFQ) has been shown to have good reliability and comparative validity for ranking nutrient intakes in young children. With the addition of food items (n 4), we aimed to re-assess the validity of the EAT FFQ and estimate calibration factors in a sub-sample of children (n 97) participating in the Growing Up Milk – Lite (GUMLi) randomised control trial (2015–2017). Participants completed the ninety-nine-item GUMLi EAT FFQ and record-assisted 24-h recalls (24HR) on two occasions. Energy and nutrient intakes were assessed at months 9 and 12 post-randomisation and calibration factors calculated to determine predicted estimates from the GUMLi EAT FFQ. Validity was assessed using Pearson correlation coefficients, weighted kappa (κ) and exact quartile categorisation. Calibration was calculated using linear regression models on 24HR, adjusted for sex and treatment group. Nutrient intakes were significantly correlated between the GUMLi EAT FFQ and 24HR at both time points. Energy-adjusted, de-attenuated Pearson correlations ranged from 0·3 (fibre) to 0·8 (Fe) at 9 months and from 0·3 (Ca) to 0·7 (Fe) at 12 months. Weighted κ for the quartiles ranged from 0·2 (Zn) to 0·6 (Fe) at 9 months and from 0·1 (total fat) to 0·5 (Fe) at 12 months. Exact agreement ranged from 30 to 74 %. Calibration factors predicted up to 56 % of the variation in the 24HR at 9 months and 44 % at 12 months. The GUMLi EAT FFQ remained a useful tool for ranking nutrient intakes with similar estimated validity compared with other FFQ used in children under 2 years.
A hallmark of the Song dynasty's achievements was the creation of a national network of state-sponsored local schools. This engendered an exponential growth of commemorative inscriptions dedicated to local government schools. Many authors used these inscriptions as an avenue to expound and disseminate their visions of schools and education. Using the methods of network analysis and document clustering, this article analyzes all the inscriptions extant from Song times for local government schools. It reveals a structural schism in the diffusion of ideas between the Upper Yangzi and other regions of the Song. It also demonstrates the growing intellectual influence of Neo-Confucian ideologues that gradually overtook that of renowned prose-writers. Methodologically, this article provides an example of how diverse digital methods enable us to handle a large body of texts from multiple perspectives and invite us to explore connections we might not have otherwise thought of.
This article gives an overview of the Local Gazetteers Research Tools (LoGaRT), including its development, technical features, methodology, and examples of research applications by members of the Tu 圖 working group. The use of LoGaRT is illustrated with four brief introductions to projects that draw on visual materials from the local gazetteers, including ritual-related illustrations, city layout maps, and maps with western cartographic features. See the websites for more detailed information on LoGaRT and other research projects using it.1
This paper focuses on the historical politics of disaster records in Chinese local gazetteers (difangzhi 地方志). Using records of mulberry crop failures as examples, the authors ask how gazetteer editors collated Yuan disaster records—initially collected to help prevent disasters and authorize the legitimacy of dynastic rule—in gazetteers and, in so doing, made them into ‘local’ knowledge. Digital humanities methods allow for both qualitative and quantitative analyses, and the authors deploy them to demonstrate how, in structured texts like the Chinese local gazetteers, they could help combine close reading of specific sections and larger-scale analysis of regional patterns. In the first part, the authors show how disasters were recorded in a Yuan Zhenjiang gazetteer to facilitate taxation and disaster prevention locally—a strategy rarely traceable in subsequent gazetteers until the Qing. In the second part, the authors shifted their perspective to the historical accumulation of data and what that reveals about the reception of Yuan disasters: whereas local gazetteers from the north generate long chronologies of mulberry disasters from the Ming to the Qing, others depict the south as disaster-free.
The Shiji (史記 Records of the Grand Historian) is of great value for Chinese history before 90 BCE. Many online databases provide character-based search of the Shiji. We go beyond simple search by creating an word-based open-access database of the Basic Annals (本纪) of the Shiji that allows the exploration of relationships between persons and the relationships between persons and named places.
We introduce the China Government Employee Database—Qing (CGED-Q), a new resource for the quantitative study of Qing officialdom. The CGED-Q details the backgrounds, characteristics and careers of Qing officials who served between 1760 and 1912, with nearly complete coverage of officials serving after 1830. We draw information on careers from the Roster of Government Personnel (jinshenlu), which in each quarterly edition listed approximately 12,500 regular civil offices and their holders in the central government and the provinces. Information about backgrounds and characteristics comes from such linked sources as lists of exam degree holders. In some years, information on military officials is also available. As of February 2020, the CGED-Q comprises 3,817,219 records, of which 3,354,897 are civil offices and the remainder are military. In this article we review the progress and prospects of the project, introduce the sources, transcription procedures, and constructed variables, and provide examples of results to showcase its potential.
Hydraulic lime binders are considered a technological marvel which revolutionized construction techniques in antiquity. The core material is made of a binder that is a mixture of calcite and hydraulic phases, which are amorphous silicate compounds that nanostructurally polymerize into insoluble phases that harden even underwater, formed during the reaction between lime and reactive silicates such as volcanic ash. This is also what makes hydraulic lime so hard to radiocarbon (14C) date. These insoluble phases contain carbonates that may set centuries following their application, resulting in younger ages, which may contaminate the calcite fraction that is favorable for 14C dating. This calcite fraction forms upon the incorporation of atmospheric carbon dioxide during the setting of the hydrated lime. Therefore, different characterization methods are being constantly developed for identifying and characterizing the components of hydraulic lime-binders. In this work, we present a rapid characterization technique based on Fourier transform infrared spectroscopy (FTIR) that characterizes the atomic disorder and chemical environment of the carbonates and silicates fractions in the binder. The atomic disorder of the calcite crystallites was determined by the ν2 and ν4 vibrational modes, and the silicates were characterized by the main peak asymmetry and full width at half maximum (FWHM). Different hydraulic binders from Caesarea Maritima were examined, including Herodian mortars from the underwater breakwater and on-land plasters and mortars from the portʼs warehouse and vaults. Hydraulic binders, in which the calcite fraction in the binder shows atomic disorder that is comparable to modern plaster binders, was associated with silicates that have asymmetry and FWHM of clays and quartz. These materials are considered to be in good preservation state for 14C dating since their carbonates crystallites are disordered and did not interact with the environment chemically to form stable and ordered crystals. Interestingly, the atomic disorder of binders that underwent chemical alterations and recrystallization processes, are associated with reactive silicates aggregates such as volcanic ash (pozzolana). These results suggest a new way to prescreen materials for radiocarbon dating based on the composition of lime-binders and preservation state of the carbonate fraction and hydraulic products.
SUSTAIN-2 (NCT02497287) was an open-label, phase III trial evaluating the safety of esketamine (ESK) nasal spray plus a newly initiated oral antidepressant (AD) for up to 1 year in adults with treatment-resistant depression (TRD). ESK is a schedule III drug that acts via glutamate receptor modulation. ESK is rapidly cleared from the plasma, and with intermittent dosing there is no accumulation. Thus, no withdrawal syndrome is expected. The current analysis assessed potential withdrawal symptoms in patients who discontinued ESK after long-term, intermittent use. In the absence of a glutamatergic-specific withdrawal scale, the Physicians Withdrawal Checklist1 (PWC-20) was used. The PWC-20 was designed to assess new or worsening benzodiazepine-like discontinuation symptoms after stopping non-SSRI anxiolytics.
ESK nasal spray was administered two times per week during a 4-week induction phase (IND). Responders entered the optimization/maintenance phase (O/M) where ESK nasal spray was dosed either weekly or every two weeks for up to 48 weeks. Patients entered a 4-week follow up period (F/U) after discontinuation from either phase, during which continuation of the AD was recommended. PWC-20 assessments were conducted at the last ESK dosing (endpoint of IND or O/M) and at weeks 1, 2 and 4 of F/U. Symptoms were rated using a 0-3-point scale (Not present = 0, Mild = 1, Moderate = 2, Severe = 3). To account for worsening of underlying depression, subset calculations were performed for depressive symptoms (PWC-DS: loss of appetite; anxiety or nervousness; irritability; dysphoric mood or depression; insomnia; fatigue, lethargy or lack of energy; restlessness or agitation; headaches; muscle aches or stiffness; weakness; difficulty concentrating or remembering; depersonalization-derealization) and withdrawal symptoms (PWC-WS: nausea and/or vomiting; diarrhea; poor coordination; diaphoresis; tremor or tremulousness; dizziness or light-headedness; increased acuity of sound, smell, or touch; paresthesias).
Data on 357 patients entering F/U were included in the analysis (91 completed treatment during the IND phase and 141 were treated during O/M). The mean (SD) PWC-20 total scores (range 0-60) at treatment endpoint, Week 1, 2 and 4 were 7.2 (6.8), 7.5(7.0), 7.4 (7.1) and 7.2 (6.9), respectively. At these same assessment times, mean PWC-WS scores (range 0-24) were 0.9 (1.7), 1.0 (1.7), 1.0 (1.8), and 0.9 (1.8). Mean PWC-DS scores (range 0-36) were 6.3 (5.6), 6.5 (5.7), 6.5 (5.8), and 6.3 (5.7), respectively. Complete analysis of data from the entire SUSTAIN-2 dataset will be presented.
No indication of drug-specific withdrawal symptoms was seen after stopping up to 1-year of intermittent treatment with ESK nasal spray for TRD.
In 2018, the Alliance for Open Media (AOMedia) finalized its first video compression format AV1, which is jointly developed by the industry consortium of leading video technology companies. The main goal of AV1 is to provide an open source and royalty-free video coding format that substantially outperforms state-of-the-art codecs available on the market in compression efficiency while remaining practical decoding complexity as well as being optimized for hardware feasibility and scalability on modern devices. To give detailed insights into how the targeted performance and feasibility is realized, this paper provides a technical overview of key coding techniques in AV1. Besides, the coding performance gains are validated by video compression tests performed with the libaom AV1 encoder against the libvpx VP9 encoder. Preliminary comparison with two leading HEVC encoders, x265 and HM, and the reference software of VVC is also conducted on AOM's common test set and an open 4k set.
Generating designs via machine learning has been an on-going challenge in computer-aided design. Recently, deep learning methods have been applied to randomly generate images in fashion, furniture and product design. However, such deep generative methods usually require a large number of training images and human aspects are not taken into account in the design process. In this work, we seek a way to involve human cognitive factors through brain activity indicated by electroencephalographic measurements (EEG) in the generative process. We propose a neuroscience-inspired design with a machine learning method where EEG is used to capture preferred design features. Such signals are used as a condition in generative adversarial networks (GAN). First, we employ a recurrent neural network Long Short-Term Memory as an encoder to extract EEG features from raw EEG signals; this data are recorded from subjects viewing several categories of images from ImageNet. Second, we train a GAN model conditioned on the encoded EEG features to generate design images. Third, we use the model to generate design images from a subject’s EEG measured brain activity. To verify our proposed generative design method, we present a case study, in which the subjects imagine the products they prefer, and the corresponding EEG signals are recorded and reconstructed by our model for evaluation. The results indicate that a generated product image with preference EEG signals gains more preference than those generated without EEG signals. Overall, we propose a neuroscience-inspired artificial intelligence design method for generating a design taking into account human preference. The method could help improve communication between designers and clients where clients might not be able to express design requests clearly.
Understanding changes in chemistry, microstructure, and physical properties during synthesis, processing, testing, and even service is vital for materials design and performance. Compared to traditional postmortem material characterization tools, in situ crystallographic characterization can provide considerable data and information on evolution of chemistry, dislocations, twinning, texture, and strains when a material is under external stimuli. Neutrons especially are able to probe material bulk properties and behaviors in extreme environments, thanks to their deep penetrating power and unique sensitivity to differentiate elements from lightweight to transition-metal atoms. In this article, we introduce and describe a diffractometer named VULCAN, which is located at Oak Ridge National Laboratory. This represents a powerful tool to understand materials properties and behaviors under complex environments, in particular, at high temperatures.