Average Number Of Contacts Research Articles

Adaptive resolution force probe simulations: Coarse graining in the ideal gas approximation.

The unfolding of molecular complexes or biomolecules under the influence of external mechanical forces can routinely be simulated with atomistic resolution. To obtain a match of the characteristic time scales with those of experimental force spectroscopy, often coarse graining procedures are employed. Here, building on a previous study, we apply the adaptive resolution scheme (AdResS) to force probe molecular dynamics (FPMD) simulations using two model systems as examples: One system is the previously investigated calix[4]arene dimer that shows reversible one-step unfolding, and the other example is provided by a small peptide, a β-alanine octamer in methanol solvent. The mechanical unfolding of this peptide proceeds via a metastable intermediate and, therefore, represents a first step toward a complex unfolding pathway. We show that the average number of native contacts serves as a robust order parameter for the forced unfolding of this small peptide. In addition to increasing the complexity of the relevant conformational changes, we study the impact of the methodology used for coarse graining. Apart from the iterative Boltzmann inversion method, we apply an ideal gas approximation, and therefore, we replace the solvent by a non-interacting system of spherical particles. In all cases, we find excellent agreement between the results of FPMD simulations performed fully atomistically and those of the AdResS simulations also in the case of fast pulling. This holds for all details of the unfolding pathways, such as the distributions of the characteristic forces and also the sequence of hydrogen-bond opening in case of the β-alanine octamer. Therefore, the methodology is very well suited to simulate the mechanical unfolding of systems of experimental relevance.

Edge-functionalized graphene quantum dot as a nano-biosensor for simultaneous detection of glucose, galactose and lactose

The swift and accurate diagnosis of diseases, particularly diabetes, remains a pressing and critical concern in healthcare. Monitoring blood glucose levels is imperative for diabetic patients to manage their condition effectively. Addressing this necessity, developing non-invasive, simultaneous detection devices for sugars shows immense promise. Herein, we introduce the design of a novel nano-biosensor employing edge‐functionalized graphene quantum dots, enabling the concurrent detection of three pivotal sugars: glucose, galactose, and lactose. Through comprehensive molecular dynamics simulations, we demonstrate the feasibility and stability of the proposed biosensor. Our results show that the edge-functionalization of graphene quantum dots significantly enhances their binding affinity, with calculated average number of contacts of 2174 for glucose, 1085 for galactose, and 6274 for lactose. Furthermore, the radial distribution function analysis echoed these findings, highlighting lactose’s pronounced interaction with the biosensor, followed by glucose and then galactose. The detailed analysis reveals distinct and non-overlapping sugar bindings on the nano-biosensor surface, with lactose showing the highest affinity and interaction strength, followed by glucose and galactose. This innovative approach marks a significant stride forward in biosensor technology, providing a potential avenue for precise and dependable monitoring of blood sugar levels in diabetic patients.

Identifying topologically associating domains using differential kernels.

Chromatin is a polymer complex of DNA and proteins that regulates gene expression. The three-dimensional (3D) structure and organization of chromatin controls DNA transcription and replication. High-throughput chromatin conformation capture techniques generate Hi-C maps that can provide insight into the 3D structure of chromatin. Hi-C maps can be represented as a symmetric matrix [Formula: see text], where each element represents the average contact probability or number of contacts between chromatin loci i and j. Previous studies have detected topologically associating domains (TADs), or self-interacting regions in [Formula: see text] within which the contact probability is greater than that outside the region. Many algorithms have been developed to identify TADs within Hi-C maps. However, most TAD identification algorithms are unable to identify nested or overlapping TADs and for a given Hi-C map there is significant variation in the location and number of TADs identified by different methods. We develop a novel method to identify TADs, KerTAD, using a kernel-based technique from computer vision and image processing that is able to accurately identify nested and overlapping TADs. We benchmark this method against state-of-the-art TAD identification methods on both synthetic and experimental data sets. We find that the new method consistently has higher true positive rates (TPR) and lower false discovery rates (FDR) than all tested methods for both synthetic and manually annotated experimental Hi-C maps. The TPR for KerTAD is also largely insensitive to increasing noise and sparsity, in contrast to the other methods. We also find that KerTAD is consistent in the number and size of TADs identified across replicate experimental Hi-C maps for several organisms. Thus, KerTAD will improve automated TAD identification and enable researchers to better correlate changes in TADs to biological phenomena, such as enhancer-promoter interactions and disease states.

Contact point marking with the OccluSense system-an invitro study on reliability and validity.

Occlusal contacts can be stained and thereby visualised employing occlusal indicators. Qualitative and quantitative indicators are differentiated. The hybrid system OccluSense supposedly combines analogue contact marking and digital registration of contacts. The reliability and validity of its contact marking have not yet been validated. The aim of this controlled randomised in-vitro study was to examine the reliability and validity of analogue contact staining with OccluSense compared to Arti-Fol and the reference standard Gnatho-Film. An experimental apparatus was designed to simulate static occlusion. The occlusal contacts were stained 50 times with Gnatho-Film to determine the average number and location of contacts registered. For comparison, the contacts were pre-stained with Gnatho-Film and then registered with Arti-Fol or OccluSense 50 times each. Every staining was statistically evaluated and compared to Gnatho-Film alone, regarding the number and location of contacts. Based on the observed characteristic staining behaviour of OccluSense, a modified evaluation strategy was developed for its colour markings (OccluSense (mod.)). Both evaluations of OccluSense determine that the same number of contacts was registered in over 94% of all cases. Neither OccluSense nor Arti-Fol stain the exact same number of contacts as Gnatho-Film, but the modified evaluation OccluSense (mod.) did improve the results for validity. When employing the modified evaluation strategy, OccluSense staining achieves similar reliability and validity as the reference standard. Pre-colouring of occlusal contacts with Gnatho-Film and the modified evaluation strategy, might become standard for analysing occlusal contacts stained by OccluSense in the future.

Improvement of microstructure of granular soil in the densification process caused by impact loading

Improvement of the mechanical properties of soil, such as density, compressibility and shear strength, is typically due to the variation in its inherent microstructure. This paper presents a microscopic study of the densification mechanism in granular soils subjected to impact loading. Both model test and discrete element simulation were carried out to quantitatively analyze the fabric evolution from a particle-scale perspective. Irregularly shaped particles were used in the simulation, on basis of which realistic packing structural information such as average contact number, contact area and branch vector length could be learned. The results reveal the microscopic densification mechanism that impact loading not only promotes the increase of contact number, but also enhances the contact area around per particle. Increasing of contact area has enriched the distribution of sutured contacts to form more steady mechanical status of soil.

Modelling the impact of human behavior using a two-layer Watts-Strogatz network for transmission and control of Mpox

PurposeThis study aims to evaluate the effectiveness of mitigation strategies and analyze the impact of human behavior on the transmission of Mpox. The results can provide guidance to public health authorities on comprehensive prevention and control for the new Mpox virus strain in the Democratic Republic of Congo as of December 2023.MethodsWe develop a two-layer Watts-Strogatz network model. The basic reproduction number is calculated using the next-generation matrix approach. Markov chain Monte Carlo (MCMC) optimization algorithm is used to fit Mpox cases in Canada into the network model. Numerical simulations are used to assess the impact of mitigation strategies and human behavior on the final epidemic size.ResultsOur results show that the contact transmission rate of low-risk groups and susceptible humans increases when the contact transmission rate of high-risk groups and susceptible humans is controlled as the Mpox epidemic spreads. The contact transmission rate of high-risk groups after May 18, 2022, is approximately 20% lower than that before May 18, 2022. Our findings indicate a positive correlation between the basic reproduction number and the level of heterogeneity in human contacts, with the basic reproduction number estimated at 2.3475 (95% CI: 0.0749–6.9084). Reducing the average number of sexual contacts to two per week effectively reduces the reproduction number to below one.ConclusionWe need to pay attention to the re-emergence of the epidemics caused by low-risk groups when an outbreak dominated by high-risk groups is under control. Numerical simulations show that reducing the average number of sexual contacts to two per week is effective in slowing down the rapid spread of the epidemic. Our findings offer guidance for the public health authorities of the Democratic Republic of Congo in developing effective mitigation strategies.

Temporal clustering of social interactions trades-off disease spreading and knowledge diffusion.

Non-pharmaceutical measures such as preventive quarantines, remote working, school and workplace closures, lockdowns, etc. have shown effectiveness from an epidemic control perspective; however, they have also significant negative consequences on social life and relationships, work routines and community engagement. In particular, complex ideas, work and school collaborations, innovative discoveries and resilient norms formation and maintenance, which often require face-to-face interactions of two or more parties to be developed and synergically coordinated, are particularly affected. In this study, we propose an alternative hybrid solution that balances the slowdown of epidemic diffusion with the preservation of face-to-face interactions, that we test simulating a disease and a knowledge spreading simultaneously on a network of contacts. Our approach involves a two-step partitioning of the population. First, we tune the level of node clustering, creating 'social bubbles' with increased contacts within each bubble and fewer outside, while maintaining the average number of contacts in each network. Second, we tune the level of temporal clustering by pairing, for a certain time interval, nodes from specific social bubbles. Our results demonstrate that a hybrid approach can achieve better trade-offs between epidemic control and complex knowledge diffusion. The versatility of our model enables tuning and refining clustering levels to optimally achieve the desired trade-off, based on the potentially changing characteristics of a disease or knowledge diffusion process.

EPIDEMIOLOGICAL CONTACT (EPICONTACT) INVESTIGATION OF COVID-19 AT ISLAMIC BOARDING SCHOOLS IN KUNINGAN REGENCY, INDONESIA

Introduction: COVID-19 has spread throughout the world with more than 61, 27 million patients infected, including in education clusters that implement boarding schools. Contact investigations on the cluster are necessary to control the spread of the virus. Aims: To describe the epidemiological contact pattern of investigation results in the Islamic Boarding School cluster in Kuningan Regency. Methods: The design of this study is descriptive with epidemiological approach. The population is all students of Pondok Pesantren X, as many as 164 students, a sample of 157 students who are positive for COVID-19, and research instrument for the COVID-19 outbreak is investigation form, the variables studied included age, gender, symptoms, duration of contact, number of contacts, number of contact groups and place of contact. Result: Univariate data analysis with epi-contact analysis show: sex: 33.3% male, 60.03% female, average age 15.05 years, the average number of contacts 3.25 people, the average number of male contacts 2.62 and female 3.39, number of male contact groups 41, number of female contact groups 91. Age of value p=0.037. Conclusions: Contact pattern conclusions are mostly in female with the number of contacts between 3-4 people and age is related to the number of contacts. Limiting contact when there is suspicion is necessary to prevent transmission.

Seeking arrangements: cell contact as a cleavage-stage biomarker

Research questionWhat can three-dimensional cell contact networks tell us about the developmental potential of cleavage-stage human embryos? DesignThis pilot study was a retrospective analysis of two Embryoscope imaging datasets from two clinics. An artificial intelligence system was used to reconstruct the three-dimensional structure of embryos from 11-plane focal stacks. Networks of cell contacts were extracted from the resulting embryo three-dimensional models and each embryo's mean contacts per cell was computed. Unpaired t-tests and receiver operating characteristic curve analysis were used to statistically analyse mean cell contact outcomes. Cell contact networks from different embryos were compared with identical embryos with similar cell arrangements. ResultsAt t4, a higher mean number of contacts per cell was associated with greater rates of blastulation and blastocyst quality. No associations were found with biochemical pregnancy, live birth, miscarriage or ploidy. At t8, a higher mean number of contacts was associated with increased blastocyst quality, biochemical pregnancy and live birth. No associations were found with miscarriage or aneuploidy. Mean contacts at t4 weakly correlated with those at t8. Four-cell embryos fell into nine distinct cell arrangements; the five most common accounted for 97% of embryos. Eight-cell embryos, however, displayed a greater degree of variation with 59 distinct cell arrangements. ConclusionsEvidence is provided for the clinical relevance of cleavage-stage cell arrangement in the human preimplantation embryo beyond the four-cell stage, which may improve selection techniques for day-3 transfers. This pilot study provides a strong case for further investigation into spatial biomarkers and three-dimensional morphokinetics.

Food availability leads to more connected contact networks among peridomestic zoonotic reservoir hosts.

The North American deermouse (Peromyscus maniculatus) is a reservoir host for many zoonotic pathogens. Deermice have been well studied, but few studies have attempted to understand social interactions within the species despite these interactions being key to understanding disease transmission. We performed an experiment to determine if supplemental food or nesting material affected social interactions of deermice and tested if interactions increased with increasing population density. We constructed three simulated buildings that received one of three treatments: food, nesting material, or control. Mice were tagged with passive integrated transponder (PIT) tags, and their movement in and out of buildings was monitored with PIT tag readers. PIT tag readings were used to create contact networks, assuming a contact if two deermice were in the same building at the same time. We found that buildings with food led to contact networks that were approximately 10 times more connected than buildings with nesting material or control buildings. We also saw a significant effect of population density on the average number of contacts per individual. These results suggest that food supplementation which is common in peridomestic settings, can significantly increase contacts between reservoir hosts, potentially leading to increased transmission of zoonotic viruses within the reservoir host and from reservoir hosts to humans.

Application of COVIDTracer to Inform Public Health Workforce Planning in Alaska During the COVID-19 Pandemic.

The COVID-19 pandemic has caused social and economic disruption worldwide and spurred numerous mitigation strategies, including state investments in training a large contact tracing and case investigation workforce. A team at the University of Alaska Anchorage evaluated implementation of the COVID-19 contact tracing and case investigation program of the State of Alaska Department of Health and Social Services, Division of Public Health, Section of Public Health Nursing. As part of that evaluation, the team used COVIDTracer, a spreadsheet modeling tool. COVIDTracer generated projections of COVID-19 case counts that informed estimates of workforce needs and case prioritization strategies. Case count projections approximated the reported epidemiologic curve with a median 7% difference in the first month. The accuracy of case count predictions declined after 1 month with a median difference of 80% in the second month. COVIDTracer inputs included previous case counts, the average length of time for telephone calls to cases and outreach to identified contacts, and the average number of contacts per case. As each variable increased, so too did estimated workforce needs. Decreasing the average time from exposure to outreach from 10 to 5 days reduced case counts estimated by COVIDTracer by approximately 93% during a 5-month period. COVIDTracer estimates informed Alaska's workforce planning and decisions about prioritizing case investigation during the pandemic. Lessons learned included the importance of being able to rapidly scale up and scale down workforce to adjust to a dynamic crisis and the limitations of prediction modeling (eg, that COVIDTracer was accurate for only about 1 month into the future). These findings may be useful for future pandemic preparedness planning and other public health emergency response activities.

Modulation of Rotational Dynamics in Halogen-Bonded Cocrystalline Solids.

Dynamic processes are responsible for the functionality of a range of materials, biomolecules, and catalysts. We report a detailed systematic study of the modulation of methyl rotational dynamics via the direct and the indirect influence of noncovalent halogen bonds. For this purpose, a novel series of cocrystalline architectures featuring halogen bonds (XB) to tetramethylpyrazine (TMP) is designed and prepared using gas-phase, solution, and solid-state mechanochemical methods. Single-crystal X-ray diffraction reveals the capacity of molecular bromine as well as weak chloro-XB donors to act as robust directional structure-directing elements. Methyl rotational barriers (Ea) measured using variable-temperature deuterium solid-state NMR range from 3.75 ± 0.04 kJ mol-1 in 1,3,5-trichloro-2,4,6-trifluorobenzene·TMP to 7.08 ± 0.15 kJ mol-1 in 1,4-dichlorotetrafluorobenzene·TMP. Ea data for a larger series of TMP cocrystals featuring chloro-, bromo-, and iodo-XB donors are shown to be governed by a combination of steric and electronic factors. The average number of carbon-carbon close contacts to the methyl group is found to be a key steric metric capable of rationalizing the observed trends within each of the Cl, Br, and I series. Differences between each series are accounted for by considering the strength of the σ-hole on the XB donor. One possible route to modulating dynamics is therefore via designer cocrystals of variable stoichiometry, maintaining the core chemical features of interest between a given donor and acceptor while simultaneously modifying the number of carbon close contacts affecting dynamics. These principles may provide design opportunities to modulate more complex geared or cascade dynamics involving larger functional groups.

Characterizing force-chain network in aggregate blend using discrete element method and complex network theory

The force chain network in aggregate blend indicates load transfer path and is the main carrier to resist external loads. The objective of this study is to analyze the force chain network characteristics of aggregate blend on the basis of complex network theory. The virtual aggregate blend models with three stone matrix asphalt (SMA) gradations and three dense asphalt concrete (AC) gradations were constructed using discrete element method (DEM). The force chain network topology structure of each aggregate blend was established according to the aggregate contact parameters extracted from DEM software and the introduced complex network theory. The characteristics of each force chain network were analyzed by the various network evaluation indicators. The results showed that there are two or more contacts between most particle pairs. The average coordination number and the average contact number of aggregate blend are not equal. The degree distribution of each gradation shows a good power-law distribution. The force chain network of aggregate blend is a scale-free network. Big particles have greater average strength and smaller average weight distribution difference compared with small particles. The reference lower limit has better clustering performance for SMA-16, and the reference upper limit has better clustering performance for AC-25. The average path length of SMA-16 is longer than that of AC-25, indicating that SMA-16 has better load transfer ability and skeleton properties.

Observational study of patients with heart failure with reduced ejection fraction (HFrEF) admitted with decompensation

Abstract Funding Acknowledgements Type of funding sources: None. Background HFrEF is associated with significant negative patient outcomes and requires substantial health care resource. Method Using the hospital registry from 1st May 2021, 100 consecutive patients were identified, who attended the heart failure clinic following their first hospitalisation with decompensated heart failure with severe LV impairment (ejection fraction <30%). Electronic records were reviewed manually. The first year is described. Results Mean age 56.8 yrs. (22-83 yrs.), 72% male, 63% were Maori/Pacific and the time to first contact was 35 days (2-177 days). Risk factors included smoking (19%), diabetes (35%), mean BMI 35.9 (17- 70), AF/AFL (33%), IHD (32%) and eGFR <60 (33%). By one year, medical therapy included beta-blocker (76% >50% target dose), RAAS inhibitor (81% >50% target dose), MRA (70%), SGLT2i (23%), diuretic (66%). The average number of outpatient contacts were 6.5 with 21% of patients having at least 1 HFrEF admission. At last review, 55% were asymptomatic with 10% receiving device therapy. Follow up imaging was performed in 83% with 78% reporting left ventricular improvement. Nine patients died, average age of 61.2 years. Conclusion Despite improving therapies, delivery by our heart failure service could be further optimised. A system co designed with our communities may provide additional advances.

Effect of vibration direction on the packing of sphero-cylinders

Particle packing is widely encountered when coping with granular materials, while mechanical vibration is usually used for packing densification. Vibration direction has been proven to be crucial for the ordered packing of spherical particles, but there are few reports for non-spherical ones in this regard. In this study, the effect of vibration direction on the macroscopic and microscopic packing parameters of sphero-cylinders are systematically examined using discrete element method (DEM). Due to the anisotropic shapes of sphero-cylinders, their packing characteristics are much richer and also more complex than those of spheres. It is found that vibration direction affects both the packing density and the packing structure of sphero-cylinders through tuning their orientation distributions and contact modes. Moreover, vibration direction plays a significant role in determining the optimal vibration intensities for dense packing. When the sphericity of Voronoi cell decreases and/or the density increases, the Nematic order parameter increases accordingly. Besides, no obvious relationship between the packing density and the average contact number is observed.

P-291 Seeking Arrangements: A New Cleavage-Stage Biomarker from 3D Morphokinetics

Abstract Study question What can we learn from 3D reconstructions of cleavage-stage embryos derived from Hoffman modulation contrast (HMC) time-lapses? Summary answer A simple spatial biomarker extracted from 3D embryo reconstructions at the t4 and t8 stages is associated with blastulation, blastocyst quality, pregnancy and live birth. What is known already Several works have demonstrated significant associations between t4 cell arrangement and blastulation potential. However, no studies have investigated the impacts of cell arrangement beyond the t4 stage in a clinical setting owing to difficulties visualising the 3D structure of embryos in a safe, cost-effective manner. In the previous ESHRE meeting, He et al. presented a deep learning system for the 3D reconstruction of cleavage-stage embryos from HMC focal stacks recorded in standard timelapse incubators. In this work, we use the aforementioned system to understand the spatial networks present in cleavage-stage embryos and investigate their associations with clinical outcomes. Study design, size, duration The study was a retrospective analysis of two imaging datasets from two different clinics. The first dataset (DS1) consisted of 162 t4 embryos with information on blastulation and Gardner grade. The second dataset (DS2) consisted of 202 embryos at t4 and t8 with information on blastocyst grade, pregnancy, live birth and PGT-A. All data was captured at 11 focal planes on Embryoscope incubators between 2018 and 2020. Participants/materials, setting, methods The system proposed by He et al. was used to reconstruct the 3D structure of embryos from their focal stacks. Networks of cell contacts were extracted from the resulting embryo 3D models and each embryo’s mean contacts per cell was computed. Statistical analysis of average cell contacts with respect to outcomes was carried out using unpaired t-tests. Moreover, cell contact networks from different embryos were compared to identify embryos with similar cell arrangements. Main results and the role of chance At t4, a higher average number of contacts per cell was associated with greater rates of blastulation in DS1 (2.59 vs 2.36, blastulated vs non-blastulated, p = 0.029) and blastocyst quality in both DS1 (2.59 vs 2.37, good vs poor, p = 0.010) and DS2 (2.51 vs 2.35, good vs poor, p = 0.017) where a ‘good’ embryo is defined as having an embryologist-provided Gardner grade with EXP>2, ICM>C and TE>C. At t8, a higher average number of contacts was associated with increased blastocyst quality (3.36 vs 3.09, good vs poor, p = 0.017), pregnancy (3.32 vs 2.87, pregnant vs not pregnant, p = 0.003) and live birth (3.40 vs 2.90, live birth vs no live birth, p = 0.0003). No associations were found with miscarriage or aneuploidy. Moreover, average contacts at t4 were not correlated with those at t8 (r = 0.15, 95% CI [-0.043, 0.34]). While 4-cell embryos fell neatly into 9 distinct cell arrangements with the 5 most common (tetrahedral, pseudotetrahedral, planar, closed-Y and linear) accounting for 95% of embryos, 8-cell embryos displayed a great degree of variation with 59 distinct cell arrangements, the largest such group representing only 8 embryos. Limitations, reasons for caution The datasets used in this study were small. Moreover, DS2 was subject to survivorship bias as it only contained embryos with PGT-A results which necessarily entailed successful blastulation. Furthermore, the 3D reconstruction system was not applicable to all cleavage-stage embryos, especially those obscured by the well or having undergone compaction. Wider implications of the findings This work provides evidence for the clinical relevance of cleavage-stage cell arrangement in the human preimplantation embryo beyond the 4-cell stage, which may improve selection techniques for D3 transfers. Moreover, our work provides a strong case for further investigation into spatial biomarkers derived from 3D embryo reconstruction and 3D morphokinetics. Trial registration number N/A

Micromechanical Analysis of Internal Instability during Shearing

Internal instability means that finer particles pass through the constrictions of coarser particles at a hydraulic gradient well below that of heave or piping, rendering the soil ineffective for its intended purpose. The soil could make a transition from an internally stable state to an unstable state or vice versa due to shear-induced deformation. The discrete element method (DEM) is adopted in this study to examine and quantify soil behavior by simulating the quasi-static shear deformation of internally stable and unstable soils at the micro- and macroscales. The dense bimodal specimens were sheared under drained conditions following a constant mean stress path in order to investigate the influence of stress heterogeneity. At the macroscale, the peak deviatoric stress was found to be a function of the fines content and the initial void ratios of the specimens. The development of the average number of contacts per particle and the stress transfer to the finer fraction during shearing are discussed. The simulation results innovatively show that a dense specimen could undergo a transition from an internally stable to an unstable soil as it dilates during shear. These numerical results have significant implications on the importance of real-life situations, such as predicting mud pumping in railroad tracks.

Abnormal chondrocyte development in a zebrafish model of cblC syndrome restored by an MMACHC cobalamin binding mutant

Variants in the MMACHC gene cause combined methylmalonic acidemia and homocystinuria cblC type, the most common inborn error of intracellular cobalamin (vitamin B12) metabolism. cblC is associated with neurodevelopmental, hematological, ocular, and biochemical abnormalities. In a subset of patients, mild craniofacial dysmorphia has also been described. Mouse models of Mmachc deletion are embryonic lethal but cause severe craniofacial phenotypes such as facial clefts. MMACHC encodes an enzyme required for cobalamin processing and variants in this gene result in the accumulation of two metabolites: methylmalonic acid (MMA) and homocysteine (HC). Interestingly, other inborn errors of cobalamin metabolism, such as cblX syndrome, are associated with mild facial phenotypes. However, the presence and severity of MMA and HC accumulation in cblX syndrome is not consistent with the presence or absence of facial phenotypes. Thus, the mechanisms by which mutations in MMACHC cause craniofacial defects are yet to be completely elucidated. Here we have characterized the craniofacial phenotypes in a zebrafish model of cblC (hg13) and performed restoration experiments with either a wildtype or a cobalamin binding deficient MMACHC protein. Homozygous mutants did not display gross morphological defects in facial development but did have abnormal chondrocyte nuclear organization and an increase in the average number of neighboring cell contacts, both phenotypes were fully penetrant. Abnormal chondrocyte nuclear organization was not associated with defects in the localization of neural crest specific markers, sox10 (RFP transgene) or barx1. Both nuclear angles and the number of neighboring cell contacts were fully restored by wildtype MMACHC and a cobalamin binding deficient variant of the MMACHC protein. Collectively, these data suggest that mutation of MMACHC causes mild to moderate craniofacial phenotypes that are independent of cobalamin binding.

Scale-free dynamics of COVID-19 in a Brazilian city

A common basis to address the dynamics of directly transmitted infectious diseases, such as COVID-19, are compartmental (or SIR) models. SIR models typically assume homogenous population mixing, a simplification that is convenient but unrealistic. Here we validate an existing model of a scale-free fractal infection process using high-resolution data on COVID-19 spread in São Caetano, Brazil. We find that transmission can be described by a network in which each infectious individual has a small number of susceptible contacts, of the order of 2–5. This model parameter correlated tightly with physical distancing measured by mobile phone data, such that in periods of greater distancing the model recovered a lower average number of contacts, and vice versa. We show that the SIR model is a special case of our scale-free fractal process model in which the parameter that reflects population structure is set at unity, indicating homogeneous mixing. Our more general framework better explained the dynamics of COVID-19 in São Caetano, used fewer parameters than a standard SIR model and accounted for geographically localized clusters of disease. Our model requires further validation in other locations and with other directly transmitted infectious agents.

Privacy-Preserving-Enabled Lightweight COVID-19 Simulation Model for Mobile Intelligent Application

In order to control the first wave of COVID-19 pandemic in 2020, many models have shown effectiveness in predicting the spread of new coronary pneumonia and the different interventions. However, few models can collect large amounts of high-quality real-time data faster under the premise of protecting privacy, considering the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant and the mass vaccination program as a new intervention. Therefore, we developed a mobile intelligent application that can collect a large amount of real-time data while protecting privacy and conducted a feasibility study by defining a new COVID-19 mathematical model SEMCVRD. By simulating different intervention measures, the prediction model of the mobile intelligent application used in this article simulates the epidemic situation in the U.K. as an example. The findings are as below: the optimal intervention strategy is to suppress the intervention at <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$P=3$ </tex-math></inline-formula> (intervention intensity: the average number of contacts per person per day) before the end of March 2021, then gradually release the intervention intensity at a rate of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$P+2$ </tex-math></inline-formula> , and finally release the intensity to <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$P=9$ </tex-math></inline-formula> in June 2021. The COVID-19 pandemic will end at the end of June 2021, when the total number of deaths will reach 128772. This strategy will be able to balance the tradeoff between loss of life and economic loss. Compared with the official statistics released by the U.K. government on May 31, 2021, our model can accurately predict the relative error rate of the total number of cases is less than 6.9%, and the relative error rate of the total number of deaths is less than 1%. Furthermore, the model is also suitable for collecting data from countries/regions around the world.