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1.
Sensors (Basel) ; 21(6)2021 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-33799343

RESUMEN

This paper revisits the stationary attitude initialization problem, i.e., the stationary alignment, of Attitude and Heading Reference Systems (AHRSs). A detailed and comprehensive error analysis is proposed for four of the most representative accelerometer- and magnetometer-based stationary attitude determination methods, namely, the Three-Axis Attitude Determination (TRIAD), the QUaternion ESTimator (QUEST), the Factored Quaternion Algorithm (FQA), and the Arc-TANgent (ATAN). For the purpose of the error analysis, constant biases in the accelerometer and magnetometer measurements are considered (encompassing, hence, the effect of hard-iron magnetism), in addition to systematic errors in the local gravity and Earth magnetic field models (flux density magnitude, declination angle, and inclination angle). The contributions of this paper are novel closed-form formulae for the residual errors (normality, orthogonality, and alignment errors) developed in the computed Direction Cosine Matrices (DCM). As a consequence, analytical insight is provided into the problem, allowing us to properly compare the performance of the investigated alignment formulations (in terms of ultimate accuracy), as well as to remove some misleading conclusions reported in previous works. The adequacy of the proposed error analysis is validated through simulation and experimental results.


Asunto(s)
Acelerometría/normas , Algoritmos , Gravitación , Magnetometría/normas , Simulación por Computador , Humanos
2.
Molecules ; 26(6)2021 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-33806967

RESUMEN

Bats are unique in their potential to serve as reservoir hosts for intracellular pathogens. Recently, the impact of COVID-19 has relegated bats from biomedical darkness to the frontline of public health as bats are the natural reservoir of many viruses, including SARS-Cov-2. Many bat genomes have been sequenced recently, and sequences coding for antimicrobial peptides are available in the public databases. Here we provide a structural analysis of genome-predicted bat cathelicidins as components of their innate immunity. A total of 32 unique protein sequences were retrieved from the NCBI database. Interestingly, some bat species contained more than one cathelicidin. We examined the conserved cysteines within the cathelin-like domain and the peptide portion of each sequence and revealed phylogenetic relationships and structural dissimilarities. The antibacterial, antifungal, and antiviral activity of peptides was examined using bioinformatic tools. The peptides were modeled and subjected to docking analysis with the region binding domain (RBD) region of the SARS-CoV-2 Spike protein. The appearance of multiple forms of cathelicidins verifies the complex microbial challenges encountered by these species. Learning more about antiviral defenses of bats and how they drive virus evolution will help scientists to investigate the function of antimicrobial peptides in these species.


Asunto(s)
Catelicidinas/química , Catelicidinas/farmacología , Quirópteros/genética , Glicoproteína de la Espiga del Coronavirus/metabolismo , Animales , Antibacterianos/química , Antibacterianos/farmacología , Antifúngicos/química , Antifúngicos/farmacología , Péptidos Catiónicos Antimicrobianos/química , Péptidos Catiónicos Antimicrobianos/farmacología , Antivirales/química , Antivirales/farmacología , Sitios de Unión , Catelicidinas/genética , Catelicidinas/metabolismo , Biología Computacional/métodos , Simulación por Computador , Genoma , Simulación del Acoplamiento Molecular , Filogenia
3.
Zhongguo Yi Liao Qi Xie Za Zhi ; 45(2): 231-236, 2021 Apr 08.
Artículo en Chino | MEDLINE | ID: mdl-33825389

RESUMEN

Accurate CT simulation is the key link of precision radiotherapy, and the performance of the localization couch of CT simulator directly affects the accuracy of radiotherapy. With the rapid development of precision radiotherapy, conventional large aperture radiotherapy special CT simulator is difficult to meet the needs of precision radiotherapy localization, so most radiotherapy centers choose high-end diagnostic CT machines equipped with a flat tabletop for radiotherapy localization. In clinical work, the performance testing of the CT simulator localization couch is easy to be ignored. In addition, there are some problems such as insufficient precision in transforming the cradle-shaped couch top of diagnostic CT into a special flat couch top for radiotherapy. This paper provided an in-depth description of the improved design and performance test of the localization couch of the first special GE Revolution CT simulator for radiotherapy introduced by West China Hospital of Sichuan University. After the improvement, all the acceptance tests of the localization couch are in line with the standard, and the performance meets the high-precision radiotherapy localization needs of patients with different body weight in the center.


Asunto(s)
Planificación de la Radioterapia Asistida por Computador , Tomografía Computarizada por Rayos X , China , Simulación por Computador , Humanos , Fantasmas de Imagen
4.
Front Public Health ; 9: 636023, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33796497

RESUMEN

This work presents simulation results for different mitigation and confinement scenarios for the propagation of COVID-19 in the metropolitan area of Madrid. These scenarios were implemented and tested using EpiGraph, an epidemic simulator which has been extended to simulate COVID-19 propagation. EpiGraph implements a social interaction model, which realistically captures a large number of characteristics of individuals and groups, as well as their individual interconnections, which are extracted from connection patterns in social networks. Besides the epidemiological and social interaction components, it also models people's short and long-distance movements as part of a transportation model. These features, together with the capacity to simulate scenarios with millions of individuals and apply different contention and mitigation measures, gives EpiGraph the potential to reproduce the COVID-19 evolution and study medium-term effects of the virus when applying mitigation methods. EpiGraph, obtains closely aligned infected and death curves related to the first wave in the Madrid metropolitan area, achieving similar seroprevalence values. We also show that selective lockdown for people over 60 would reduce the number of deaths. In addition, evaluate the effect of the use of face masks after the first wave, which shows that the percentage of people that comply with mask use is a crucial factor for mitigating the infection's spread.


Asunto(s)
/transmisión , Simulación por Computador , Red Social , Algoritmos , /prevención & control , Ciudades , Control de Enfermedades Transmisibles , Epidemias , Humanos , Máscaras , Cuarentena , Estudios Seroepidemiológicos , España , Viaje
5.
Int J Mol Sci ; 22(6)2021 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-33809918

RESUMEN

Linear B-cell epitope prediction research has received a steadily growing interest ever since the first method was developed in 1981. B-cell epitope identification with the help of an accurate prediction method can lead to an overall faster and cheaper vaccine design process, a crucial necessity in the COVID-19 era. Consequently, several B-cell epitope prediction methods have been developed over the past few decades, but without significant success. In this study, we review the current performance and methodology of some of the most widely used linear B-cell epitope predictors which are available via a command-line interface, namely, BcePred, BepiPred, ABCpred, COBEpro, SVMTriP, LBtope, and LBEEP. Additionally, we attempted to remedy performance issues of the individual methods by developing a consensus classifier, which combines the separate predictions of these methods into a single output, accelerating the epitope-based vaccine design. While the method comparison was performed with some necessary caveats and individual methods might perform much better for specialized datasets, we hope that this update in performance can aid researchers towards the choice of a predictor, for the development of biomedical applications such as designed vaccines, diagnostic kits, immunotherapeutics, immunodiagnostic tests, antibody production, and disease diagnosis and therapy.


Asunto(s)
Biología Computacional/métodos , Mapeo Epitopo/métodos , Epítopos de Linfocito B/química , Vacunas/química , Simulación por Computador , Diseño de Fármacos , Epítopos de Linfocito B/metabolismo , Humanos , /metabolismo , Vacunas/metabolismo
6.
Int J Mol Sci ; 22(6)2021 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-33802169

RESUMEN

In order to treat Coronavirus Disease 2019 (COVID-19), we predicted and implemented a drug delivery system (DDS) that can provide stable drug delivery through a computational approach including a clustering algorithm and the Schrödinger software. Six carrier candidates were derived by the proposed method that could find molecules meeting the predefined conditions using the molecular structure and its functional group positional information. Then, just one compound named glycyrrhizin was selected as a candidate for drug delivery through the Schrödinger software. Using glycyrrhizin, nafamostat mesilate (NM), which is known for its efficacy, was converted into micelle nanoparticles (NPs) to improve drug stability and to effectively treat COVID-19. The spherical particle morphology was confirmed by transmission electron microscopy (TEM), and the particle size and stability of 300-400 nm were evaluated by measuring DLSand the zeta potential. The loading of NM was confirmed to be more than 90% efficient using the UV spectrum.


Asunto(s)
/tratamiento farmacológico , Biología Computacional/métodos , Sistemas de Liberación de Medicamentos/métodos , Células A549 , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Benzamidinas/química , Benzamidinas/uso terapéutico , Supervivencia Celular/efectos de los fármacos , Análisis por Conglomerados , Simulación por Computador , Bases de Datos Farmacéuticas , Portadores de Fármacos/química , Reposicionamiento de Medicamentos , Estabilidad de Medicamentos , Ácido Glicirrínico/química , Ácido Glicirrínico/uso terapéutico , Guanidinas/química , Guanidinas/uso terapéutico , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Micelas , Microscopía Electrónica de Transmisión , Estructura Molecular , Nanopartículas/química , Tamaño de la Partícula
7.
Zoolog Sci ; 38(2): 170-178, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33812356

RESUMEN

The exumbrellar surfaces of six pelagic cnidarians from three classes were ultra-structurally compared to reveal their structural diversity in relation to their gelatinous, transparent bodies. We examined two hydrozoans (Diphyes chamissonis and Colobonema sericeum), a cubozoan (Chironex yamaguchii), and three scyphozoans (Atolla vanhöffeni, Aurelia coerulea, and Mastigias papua). The exumbrellar surfaces of the mesoglea in D. chamissonis, Ch. yamaguchii, Au. coerulea, and M. papua were covered with a simple epidermis; the shapes of the epidermal cells were remarkably different among the species. The epidermal cells of Ch. yamaguchii and M. papua possessed an array of microvilli on the apical side. The array possibly reduced light reflectance and provided some other surface properties, as seen for the cuticular nipple array in tunicates, considering the length, width, and pitch of the microvilli. The reduction of light reflectance on the array of microvilli was supported by the simulation with rigorous coupled wave analysis (RCWA). Microvilli were sparse and did not form an array in metephyrae of Au. coerulea. The mesoglea matrix beneath the basal side of the epidermis was loose in all of the species. The exumbrellar side of the mesoglea was exposed only in the mesopelagic species, At. vanhöffeni and Co. sericeum, and electron-dense layer(s) covered the surface of the mesoglea. It is uncertain whether the exumbrellar epidermis is absent in these species or the epidermal cells are completely exfoliated during the sampling and handling processes. In the latter case, the electron-dense layer(s) on the mesoglea surface might originally underlie the epidermis.


Asunto(s)
Cubomedusas/ultraestructura , Hidrozoos/ultraestructura , Escifozoos/ultraestructura , Animales , Simulación por Computador , Luz , Modelos Biológicos
8.
Comput Math Methods Med ; 2021: 6664483, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33815565

RESUMEN

In this study, we propose a new mathematical model and analyze it to understand the transmission dynamics of the COVID-19 pandemic in Bangkok, Thailand. It is divided into seven compartmental classes, namely, susceptible (S), exposed (E), symptomatically infected (I s ), asymptomatically infected (I a ), quarantined (Q), recovered (R), and death (D), respectively. The next-generation matrix approach was used to compute the basic reproduction number denoted as R cvd19 of the proposed model. The results show that the disease-free equilibrium is globally asymptotically stable if R cvd19 < 1. On the other hand, the global asymptotic stability of the endemic equilibrium occurs if R cvd19 > 1. The mathematical analysis of the model is supported using numerical simulations. Moreover, the model's analysis and numerical results prove that the consistent use of face masks would go on a long way in reducing the COVID-19 pandemic.


Asunto(s)
/epidemiología , Modelos Biológicos , Pandemias/estadística & datos numéricos , Número Básico de Reproducción , Simulación por Computador , Susceptibilidad a Enfermedades , Humanos , Máscaras , Conceptos Matemáticos , Pandemias/prevención & control , Tailandia/epidemiología
9.
J Biol Dyn ; 15(1): 195-212, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-33827379

RESUMEN

Incidence vs. Cumulative Cases (ICC) curves are introduced and shown to provide a simple framework for parameter identification in the case of the most elementary epidemiological model, consisting of susceptible, infected, and removed compartments. This novel methodology is used to estimate the basic reproduction ratio of recent outbreaks, including those associated with the ongoing COVID-19 pandemic.


Asunto(s)
/epidemiología , Pandemias/estadística & datos numéricos , Número Básico de Reproducción/estadística & datos numéricos , China/epidemiología , Simulación por Computador , Susceptibilidad a Enfermedades , Gastroenteritis/epidemiología , Humanos , Incidencia , Conceptos Matemáticos , Modelos Biológicos , Modelos Estadísticos , Dinámicas no Lineales , Distribución de Poisson , Relación Señal-Ruido , España/epidemiología
10.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(3): 430-438, 2021 Mar 25.
Artículo en Chino | MEDLINE | ID: mdl-33849836

RESUMEN

OBJECTIVE: To explore the biomechanical mechanism of blunt spleen injury based on finite element analysis. OBJECTIVE: A fist finite element model was used to simulate the impact at 4-8 m/s in the spleen area of THUMS4.0 human body model from the front of the left costal area, the left anterior axillary line and the rear scapular line. The strain distribution and damage of the spleen under different conditions were observed. The simulation results were compared with the clinical cases of spleen rupture to analyze the mechanism of spleen injury. OBJECTIVE: The damage location and strain distribution of the spleen could vary under different conditions. Due to the special anatomical location of the spleen, a blunt impact at the speed of 4-8 m/s on the front side did not easily cause spleen injury, and the strain was distributed mainly in the front of the spleen and the spleen hilum; a similar blunt impact on the left side was likely to cause spleen diaphragmatic surface injury, the splenic visceral surface could be injured by the compression of the medial tissue and organs and the traction of the splenic pedicle, and the strain was distributed in the spleen diaphragmatic and visceral surfaces; an impact on the back side was likely to cause injuries in the posterior portion and hilum of the spleen, and the strain was mainly concentrated in the injured area. OBJECTIVE: Blunt spleen injuries caused by punches on the abdomen are mostly caused by direct impact on the ribs, the compression by the surrounding tissues and organs and the traction by the spleen pedicle.


Asunto(s)
Bazo , Heridas no Penetrantes , Abdomen , Fenómenos Biomecánicos , Simulación por Computador , Análisis de Elementos Finitos , Humanos
11.
Science ; 372(6537)2021 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-33795432

RESUMEN

Multivalent display of receptor-engaging antibodies or ligands can enhance their activity. Instead of achieving multivalency by attachment to preexisting scaffolds, here we unite form and function by the computational design of nanocages in which one structural component is an antibody or Fc-ligand fusion and the second is a designed antibody-binding homo-oligomer that drives nanocage assembly. Structures of eight nanocages determined by electron microscopy spanning dihedral, tetrahedral, octahedral, and icosahedral architectures with 2, 6, 12, and 30 antibodies per nanocage, respectively, closely match the corresponding computational models. Antibody nanocages targeting cell surface receptors enhance signaling compared with free antibodies or Fc-fusions in death receptor 5 (DR5)-mediated apoptosis, angiopoietin-1 receptor (Tie2)-mediated angiogenesis, CD40 activation, and T cell proliferation. Nanocage assembly also increases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus neutralization by α-SARS-CoV-2 monoclonal antibodies and Fc-angiotensin-converting enzyme 2 (ACE2) fusion proteins.


Asunto(s)
Anticuerpos/química , Anticuerpos/inmunología , Nanoestructuras , Ingeniería de Proteínas , Transducción de Señal , Angiopoyetinas/química , Angiopoyetinas/inmunología , Angiopoyetinas/metabolismo , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/química , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/química , Anticuerpos Antivirales/inmunología , Linfocitos B/inmunología , Antígenos CD40/química , Antígenos CD40/inmunología , Antígenos CD40/metabolismo , Línea Celular Tumoral , Proliferación Celular , Simulación por Computador , Genes Sintéticos , Humanos , Fragmentos Fc de Inmunoglobulinas/química , Activación de Linfocitos , Modelos Moleculares , Unión Proteica , Receptor TIE-2/metabolismo , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/inmunología , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Linfocitos T/inmunología , Linfocitos T/fisiología
12.
Molecules ; 26(7)2021 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-33805419

RESUMEN

The COVID-19 pandemic has reached over 100 million worldwide. Due to the multi-targeted nature of the virus, it is clear that drugs providing anti-COVID-19 effects need to be developed at an accelerated rate, and a combinatorial approach may stand to be more successful than a single drug therapy. Among several targets and pathways that are under investigation, the renin-angiotensin system (RAS) and specifically angiotensin-converting enzyme (ACE), and Ca2+-mediated SARS-CoV-2 cellular entry and replication are noteworthy. A combination of ACE inhibitors and calcium channel blockers (CCBs), a critical line of therapy for pulmonary hypertension, has shown therapeutic relevance in COVID-19 when investigated independently. To that end, we conducted in silico modeling using BIOiSIM, an AI-integrated mechanistic modeling platform by utilizing known preclinical in vitro and in vivo datasets to accurately simulate systemic therapy disposition and site-of-action penetration of the CCBs and ACEi compounds to tissues implicated in COVID-19 pathogenesis.


Asunto(s)
Antivirales/farmacocinética , Reposicionamiento de Medicamentos/métodos , Hipertensión Pulmonar/tratamiento farmacológico , Inhibidores de la Enzima Convertidora de Angiotensina/farmacocinética , Antivirales/sangre , Biosimilares Farmacéuticos , Bloqueadores de los Canales de Calcio/farmacocinética , Simulación por Computador , Bases de Datos Farmacéuticas , Desarrollo de Medicamentos/métodos , Humanos , Hipertensión Pulmonar/virología , Distribución Tisular
13.
Nat Commun ; 12(1): 2060, 2021 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-33824323

RESUMEN

Cancer growth can be described as a caricature of the renewal process of the tissue of origin, where the tissue architecture has a strong influence on the evolutionary dynamics within the tumor. Using a classic, well-studied model of tumor evolution (a passenger-driver mutation model) we systematically alter spatial constraints and cell mixing rates to show how tissue structure influences functional (driver) mutations and genetic heterogeneity over time. This approach explores a key mechanism behind both inter-patient and intratumoral tumor heterogeneity: competition for space. Time-varying competition leads to an emergent transition from Darwinian premalignant growth to subsequent invasive neutral tumor growth. Initial spatial constraints determine the emergent mode of evolution (Darwinian to neutral) without a change in cell-specific mutation rate or fitness effects. Driver acquisition during the Darwinian precancerous stage may be modulated en route to neutral evolution by the combination of two factors: spatial constraints and limited cellular mixing. These two factors occur naturally in ductal carcinomas, where the branching topology of the ductal network dictates spatial constraints and mixing rates.


Asunto(s)
Progresión de la Enfermedad , Neoplasias/patología , Especificidad de Órganos , División Celular , Simulación por Computador , Heterogeneidad Genética , Humanos , Imagenología Tridimensional , Modelos Biológicos
14.
BMC Bioinformatics ; 22(1): 170, 2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33789571

RESUMEN

BACKGROUND: The most common measure of association between two continuous variables is the Pearson correlation (Maronna et al. in Safari an OMC. Robust statistics, 2019. https://login.proxy.bib.uottawa.ca/login?url=https://learning.oreilly.com/library/view/-/9781119214687/?ar&orpq&email=^u). When outliers are present, Pearson does not accurately measure association and robust measures are needed. This article introduces three new robust measures of correlation: Taba (T), TabWil (TW), and TabWil rank (TWR). The correlation estimators T and TW measure a linear association between two continuous or ordinal variables; whereas TWR measures a monotonic association. The robustness of these proposed measures in comparison with Pearson (P), Spearman (S), Quadrant (Q), Median (M), and Minimum Covariance Determinant (MCD) are examined through simulation. Taba distance is used to analyze genes, and statistical tests were used to identify those genes most significantly associated with Williams Syndrome (WS). RESULTS: Based on the root mean square error (RMSE) and bias, the three proposed correlation measures are highly competitive when compared to classical measures such as P and S as well as robust measures such as Q, M, and MCD. Our findings indicate TBL2 was the most significant gene among patients diagnosed with WS and had the most significant reduction in gene expression level when compared with control (P value = 6.37E-05). CONCLUSIONS: Overall, when the distribution is bivariate Log-Normal or bivariate Weibull, TWR performs best in terms of bias and T performs best with respect to RMSE. Under the Normal distribution, MCD performs well with respect to bias and RMSE; but TW, TWR, T, S, and P correlations were in close proximity. The identification of TBL2 may serve as a diagnostic tool for WS patients. A Taba R package has been developed and is available for use to perform all necessary computations for the proposed methods.


Asunto(s)
Correlación de Datos , Simulación por Computador , Humanos
15.
Sci Rep ; 11(1): 4891, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33649364

RESUMEN

Contact tracing can play a key role in controlling human-to-human transmission of a highly contagious disease such as COVID-19. We investigate the benefits and costs of contact tracing in the COVID-19 transmission. We estimate two unknown epidemic model parameters (basic reproductive number [Formula: see text] and confirmed rate [Formula: see text]) by using confirmed case data. We model contact tracing in a two-layer network model. The two-layer network is composed by the contact network in the first layer and the tracing network in the second layer. In terms of benefits, simulation results show that increasing the fraction of traced contacts decreases the size of the epidemic. For example, tracing [Formula: see text] of the contacts is enough for any reopening scenario to reduce the number of confirmed cases by half. Considering the act of quarantining susceptible households as the contact tracing cost, we have observed an interesting phenomenon. The number of quarantined susceptible people increases with the increase of tracing because each individual confirmed case is mentioning more contacts. However, after reaching a maximum point, the number of quarantined susceptible people starts to decrease with the increase of tracing because the increment of the mentioned contacts is balanced by a reduced number of confirmed cases. The goal of this research is to assess the effectiveness of contact tracing for the containment of COVID-19 spreading in the different movement levels of a rural college town in the USA. Our research model is designed to be flexible and therefore, can be used to other geographic locations.


Asunto(s)
Simulación por Computador , Trazado de Contacto , Modelos Biológicos , Población Rural , Adolescente , Adulto , /transmisión , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estados Unidos/epidemiología
16.
Int J Mol Med ; 47(4)2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33649798

RESUMEN

Severe acute respiratory syndrome (SARS) coronavirus­2 (SARS­CoV­2), the causative viral agent for the ongoing COVID­19 pandemic, enters its host cells primarily via the binding of the SARS­CoV­2 spike (S) proteins to the angiotensin­converting enzyme 2 (ACE2). A number of other cell entry mediators have also been identified, including neuropilin­1 (NRP1) and transmembrane protease serine 2 (TMPRSS2). More recently, it has been demonstrated that transmembrane protease serine 4 (TMPRSS4) along with TMPRSS2 activate the SARS­CoV­2 S proteins, and enhance the viral infection of human small intestinal enterocytes. To date, a systematic analysis of TMPRSS4 in health and disease is lacking. In the present study, using in silico tools, the gene expression and genetic alteration of TMPRSS4 were analysed across numerous tumours and compared to controls. The observations were also expanded to the level of the central nervous system (CNS). The findings revealed that TMPRSS4 was overexpressed in 11 types of cancer, including lung adenocarcinoma, lung squamous cell carcinoma, cervical squamous cell carcinoma, thyroid carcinoma, ovarian cancer, cancer of the rectum, pancreatic cancer, colon and stomach adenocarcinoma, uterine carcinosarcoma and uterine corpus endometrial carcinoma, whilst it was significantly downregulated in kidney carcinomas, acute myeloid leukaemia, skin cutaneous melanoma and testicular germ cell tumours. Finally, a high TMPRSS4 expression was documented in the olfactory tubercle, paraolfactory gyrus and frontal operculum, all brain regions which are associated with the sense of smell and taste. Collectively, these data suggest that TMPRSS4 may play a role in COVID­19 symptomatology as another SARS­CoV­2 host cell entry mediator responsible for the tropism of this coronavirus both in the periphery and the CNS.


Asunto(s)
/enzimología , Proteínas de la Membrana/genética , /patogenicidad , Serina Endopeptidasas/genética , Internalización del Virus , Encéfalo/enzimología , Sistema Nervioso Central/enzimología , Simulación por Computador , Bases de Datos Genéticas , Femenino , Tracto Gastrointestinal/enzimología , Perfilación de la Expresión Génica , Interacciones Microbiota-Huesped/genética , Interacciones Microbiota-Huesped/fisiología , Humanos , Masculino , Proteínas de la Membrana/fisiología , Neoplasias/enzimología , Neoplasias/genética , Pandemias , Serina Endopeptidasas/fisiología
17.
Sci Rep ; 11(1): 6264, 2021 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-33731722

RESUMEN

Many educational institutions have partially or fully closed all operations to cope with the challenges of the ongoing COVID-19 pandemic. In this paper, we explore strategies that such institutions can adopt to conduct safe reopening and resume operations during the pandemic. The research is motivated by the University of Illinois at Urbana-Champaign's (UIUC's) SHIELD program, which is a set of policies and strategies, including rapid saliva-based COVID-19 screening, for ensuring safety of students, faculty and staff to conduct in-person operations, at least partially. Specifically, we study how rapid bulk testing, contact tracing and preventative measures such as mask wearing, sanitization, and enforcement of social distancing can allow institutions to manage the epidemic spread. This work combines the power of analytical epidemic modeling, data analysis and agent-based simulations to derive policy insights. We develop an analytical model that takes into account the asymptomatic transmission of COVID-19, the effect of isolation via testing (both in bulk and through contact tracing) and the rate of contacts among people within and outside the institution. Next, we use data from the UIUC SHIELD program and 85 other universities to estimate parameters that describe the analytical model. Using the estimated parameters, we finally conduct agent-based simulations with various model parameters to evaluate testing and reopening strategies. The parameter estimates from UIUC and other universities show similar trends. For example, infection rates at various institutions grow rapidly in certain months and this growth correlates positively with infection rates in counties where the universities are located. Infection rates are also shown to be negatively correlated with testing rates at the institutions. Through agent-based simulations, we demonstrate that the key to designing an effective reopening strategy is a combination of rapid bulk testing and effective preventative measures such as mask wearing and social distancing. Multiple other factors help to reduce infection load, such as efficient contact tracing, reduced delay between testing and result revelation, tests with less false negatives and targeted testing of high-risk class among others. This paper contributes to the nascent literature on combating the COVID-19 pandemic and is especially relevant for educational institutions and similarly large organizations. We contribute by providing an analytical model that can be used to estimate key parameters from data, which in turn can be used to simulate the effect of different strategies for reopening. We quantify the relative effect of different strategies such as bulk testing, contact tracing, reduced infectivity and contact rates in the context of educational institutions. Specifically, we show that for the estimated average base infectivity of 0.025 ([Formula: see text]), a daily number of tests to population ratio T/N of 0.2, i.e., once a week testing for all individuals, is a good indicative threshold. However, this test to population ratio is sensitive to external infectivities, internal and external mobilities, delay in getting results after testing, and measures related to mask wearing and sanitization, which affect the base infection rate.


Asunto(s)
/prevención & control , Pandemias/prevención & control , Instituciones Académicas/normas , Universidades/normas , Enfermedades Asintomáticas , Simulación por Computador , Trazado de Contacto/métodos , Humanos , Saliva/virología
18.
World J Pediatr Congenit Heart Surg ; 12(2): 234-243, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33683998

RESUMEN

BACKGROUND: In pediatric cardiac surgery, an application of three-dimensional (3D) modeling to develop custom-made prostheses is limited, and currently surgeons use their intraoperative visual estimation to develop 3D complex structures from 2D patch materials. Contemporary 3D designers are developing complex surfaces using surface modeling in other industries, which can be applied to pediatric cardiac surgery. However, its free-form nature may lead to intradesigner variability. METHODS: A patient with a body weight of 4 kg with partial anomalous pulmonary venous connection and preoperative computed tomography data was selected, and a patient-specific 3D heart model was obtained. Through collaboration with a pediatric cardiologist and a pediatric cardiac surgeon, a 3D designer developed two patient-specific 3D patches for an intra-atrial rerouting procedure (IAR) for the patient using different methods of surface modeling. The shape and size of two flattened patches were analyzed using a geometric morphometrics (GM) approach. Computational fluid dynamics (CFD) analysis was also performed to calculate pressure drop across streamlines and flow energy loss in the right atrium for both patches. RESULTS: The GM analysis showed that the size and shape of the two patches around the systemic vein orifice, crucial to prevent systemic venous obstruction, were almost equivalent. However, the CFD analysis showed that the pressure drop and flow energy loss were almost twice for one patch compared with the other. CONCLUSIONS: Our platform of developing a patient-specific 3D patch for an IAR procedure using surface modeling seemed promising, although intradesigner patch variability was not neglectable in our small-sized patient.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos/métodos , Simulación por Computador , Atrios Cardíacos/cirugía , Cardiopatías Congénitas/cirugía , Imagenología Tridimensional/métodos , Niño , Atrios Cardíacos/diagnóstico por imagen , Cardiopatías Congénitas/diagnóstico , Humanos , Tomografía Computarizada por Rayos X
19.
Proc Natl Acad Sci U S A ; 118(14)2021 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-33741734

RESUMEN

Increasing evidence indicates that superspreading plays a dominant role in COVID-19 transmission. Recent estimates suggest that the dispersion parameter k for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is on the order of 0.1, which corresponds to about 10% of cases being the source of 80% of infections. To investigate how overdispersion might affect the outcome of various mitigation strategies, we developed an agent-based model with a social network that allows transmission through contact in three sectors: "close" (a small, unchanging group of mutual contacts as might be found in a household), "regular" (a larger, unchanging group as might be found in a workplace or school), and "random" (drawn from the entire model population and not repeated regularly). We assigned individual infectivity from a gamma distribution with dispersion parameter k We found that when k was low (i.e., greater heterogeneity, more superspreading events), reducing random sector contacts had a far greater impact on the epidemic trajectory than did reducing regular contacts; when k was high (i.e., less heterogeneity, no superspreading events), that difference disappeared. These results suggest that overdispersion of COVID-19 transmission gives the virus an Achilles' heel: Reducing contacts between people who do not regularly meet would substantially reduce the pandemic, while reducing repeated contacts in defined social groups would be less effective.


Asunto(s)
/epidemiología , Trazado de Contacto/estadística & datos numéricos , Modelos Estadísticos , Pandemias , Factores de Edad , /virología , Simulación por Computador , Humanos , Cuarentena/estadística & datos numéricos , /fisiología , Red Social
20.
J Environ Radioact ; 232: 106573, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33751985

RESUMEN

A new measurement model composed of High Purity Germanium detector HPGe including Lead Shield with a mixed source of Am-241, Cd-109, …in a soil matrix packed in a cylindrical container was developed by Monte Carlo N-Particles code MCNP5. The Monte Carlo models being largely used for efficiencies calculations in routine environmental radioactivity measurements of high volume soil samples. In order to validate the simulation, a multi-radionuclides soil matrix source in a cylindrical container is prepared. Comparing the simulated results to the experimental ones, allows us to correct coincidence summing in the soil standard and study its effect in activity measurements where a good agreement is found between corrected activities and results found by another geometry and show how uncorrected efficiency curves lead to erroneous activity calculation. Finally, the developed model is applied to study the distribution of natural and artificial radioactivity in a forest site in Bainem, northern of Algeria, these results are invested for radiological impact and soil erosion studies in the study Area.


Asunto(s)
Monitoreo de Radiación , Espectrometría gamma , Simulación por Computador , Método de Montecarlo , Radioisótopos/análisis
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