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1.
Biometrics ; 79(3): 2143-2156, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-35848417

RESUMO

Many bioinformatics pipelines include tests for equilibrium. Tests for diploids are well studied and widely available, but extending these approaches to autopolyploids is hampered by the presence of double reduction, the comigration of sister chromatid segments into the same gamete during meiosis. Though a hindrance for equilibrium tests, double reduction rates are quantities of interest in their own right, as they provide insights about the meiotic behavior of autopolyploid organisms. Here, we develop procedures to (i) test for equilibrium while accounting for double reduction, and (ii) estimate the double reduction rate given equilibrium. To do so, we take two approaches: a likelihood approach, and a novel U-statistic minimization approach that we show generalizes the classical equilibrium χ2 test in diploids. For small sample sizes and uncertain genotypes, we further develop a bootstrap procedure based on our U-statistic to test for equilibrium. We validate our methods on both simulated and real data.


Assuntos
Modelos Genéticos , Funções Verossimilhança , Genótipo
2.
BMC Gastroenterol ; 23(1): 146, 2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37170191

RESUMO

BACKGROUND: Inadequate bowel preparation for colonoscopy remains an issue resulting in lower adenoma detection rates and increased cost. We assessed the efficacy, safety and tolerability of high-dose bowel preparations in subjects who previously had an inadequate colonoscopy preparation. METHODS: We performed a multi-step prospective trial of high-dose bowel preparations with subjects assigned to the dose higher than their previous inadequate preparation. Step 1: 1.5 times the standard-dose of polyethylene glycol 3350 (PEG, 459 g) and Gatorade; and Step 2: 2.0 times the standard-dose of PEG (612 g) and Gatorade, both were given as extended split-dose preparations. 69 outpatients consumed their preparation before a morning colonoscopy. The primary endpoint was colon cleanliness assessed by the Chicago bowel preparation scale (BPS). Safety was assessed by comparing a baseline basic metabolic panel (BMP) to a post-cleansing BMP. Patients with no history of inadequate colon cleansing who consumed standard doses of PEG (306 g to 357 g) and Gatorade were used as a comparison group. Tolerability of the bowel preparation was assessed using a subject-questionnaire. RESULTS: When compared to controls consuming standard-dose bowel preparations, subjects consuming high-dose preparations had no statistically significant difference in colon cleanliness as measured by the modified or total Chicago BPS scores or differences in tolerability. Baseline and post-cleaning BMPs were not significantly different other than the BUN falling (p < 0.0001) after the preparation. CONCLUSIONS: The multi-step high-dose bowel cleansing protocol proved highly efficacious, safe and well tolerated in subjects who previously had an inadequate colonoscopy preparation. TRIAL REGISTRATION: ClinicalTrials.gov NCT02661750.


Assuntos
Catárticos , Polietilenoglicóis , Humanos , Catárticos/efeitos adversos , Colonoscopia/métodos , Polietilenoglicóis/efeitos adversos , Estudos Prospectivos
3.
Biostatistics ; 21(1): 15-32, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29985984

RESUMO

We combine two important ideas in the analysis of large-scale genomics experiments (e.g. experiments that aim to identify genes that are differentially expressed between two conditions). The first is use of Empirical Bayes (EB) methods to handle the large number of potentially-sparse effects, and estimate false discovery rates and related quantities. The second is use of factor analysis methods to deal with sources of unwanted variation such as batch effects and unmeasured confounders. We describe a simple modular fitting procedure that combines key ideas from both these lines of research. This yields new, powerful EB methods for analyzing genomics experiments that account for both sparse effects and unwanted variation. In realistic simulations, these new methods provide significant gains in power and calibration over competing methods. In real data analysis, we find that different methods, while often conceptually similar, can vary widely in their assessments of statistical significance. This highlights the need for care in both choice of methods and interpretation of results.


Assuntos
Genômica/métodos , Modelos Estatísticos , Humanos
4.
Bioinformatics ; 36(6): 1795-1800, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32176767

RESUMO

MOTIVATION: Empirical Bayes techniques to genotype polyploid organisms usually either (i) assume technical artifacts are known a priori or (ii) estimate technical artifacts simultaneously with the prior genotype distribution. Case (i) is unappealing as it places the onus on the researcher to estimate these artifacts, or to ensure that there are no systematic biases in the data. However, as we demonstrate with a few empirical examples, case (ii) makes choosing the class of prior genotype distributions extremely important. Choosing a class is either too flexible or too restrictive results in poor genotyping performance. RESULTS: We propose two classes of prior genotype distributions that are of intermediate levels of flexibility: the class of proportional normal distributions and the class of unimodal distributions. We provide a complete characterization of and optimization details for the class of unimodal distributions. We demonstrate, using both simulated and real data that using these classes results in superior genotyping performance. AVAILABILITY AND IMPLEMENTATION: Genotyping methods that use these priors are implemented in the updog R package available on the Comprehensive R Archive Network: https://cran.r-project.org/package=updog. All code needed to reproduce the results of this article is available on GitHub: https://github.com/dcgerard/reproduce_prior_sims. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Poliploidia , Software , Teorema de Bayes , Genótipo , Técnicas de Genotipagem , Humanos
5.
Heredity (Edinb) ; 127(4): 357-362, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34373594

RESUMO

Linkage disequilibrium (LD) estimates are often calculated genome-wide for use in many tasks, such as SNP pruning and LD decay estimation. However, in the presence of genotype uncertainty, naive approaches to calculating LD have extreme attenuation biases, incorrectly suggesting that SNPs are less dependent than in reality. These biases are particularly strong in polyploid organisms, which often exhibit greater levels of genotype uncertainty than diploids. A principled approach using maximum likelihood estimation with genotype likelihoods can reduce this bias, but is prohibitively slow for genome-wide applications. Here, we present scalable moment-based adjustments to LD estimates based on the marginal posterior distributions of the genotypes. We demonstrate, on both simulated and real data, that these moment-based estimators are as accurate as maximum likelihood estimators, but are almost as fast as naive approaches based only on posterior mean genotypes. This opens up bias-corrected LD estimation to genome-wide applications. In addition, we provide standard errors for these moment-based estimators. All methods discussed in this manuscript are implemented in the ldsep package, available on the Comprehensive R Archive Network ( https://cran.r-project.org/package=ldsep ).


Assuntos
Polimorfismo de Nucleotídeo Único , Viés , Genótipo , Desequilíbrio de Ligação , Incerteza
6.
Stat Sin ; 31(3): 1145-1166, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38148787

RESUMO

Unwanted variation, including hidden confounding, is a well-known problem in many fields, but particularly in large-scale gene expression studies. Recent proposals to use control genes, genes assumed to be unassociated with the covariates of interest, have led to new methods to deal with this problem. Several versions of these removing unwanted variation (RUV) methods have been proposed, including RUV1, RUV2, RUV4, RUVinv, RUVrinv, and RUVfun. Here, we introduce a general framework, RUV*, that both unites and generalizes these approaches. This unifying framework helps clarify the connections between existing methods. In particular, we provide conditions under which RUV2 and RUV4 are equivalent. The RUV* framework preserves an advantage of the RUV approaches, namely, their modularity, which facilitates the development of novel methods based on existing matrix imputation algorithms. We illustrate this by implementing RUVB, a version of RUV* based on Bayesian factor analysis. In realistic simulations based on real data, we found RUVB to be competitive with existing methods in terms of both power and calibration. However, providing a consistently reliable calibration among the data sets remains challenging.

7.
BMC Bioinformatics ; 21(1): 206, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32448189

RESUMO

BACKGROUND: With the explosion in the number of methods designed to analyze bulk and single-cell RNA-seq data, there is a growing need for approaches that assess and compare these methods. The usual technique is to compare methods on data simulated according to some theoretical model. However, as real data often exhibit violations from theoretical models, this can result in unsubstantiated claims of a method's performance. RESULTS: Rather than generate data from a theoretical model, in this paper we develop methods to add signal to real RNA-seq datasets. Since the resulting simulated data are not generated from an unrealistic theoretical model, they exhibit realistic (annoying) attributes of real data. This lets RNA-seq methods developers assess their procedures in non-ideal (model-violating) scenarios. Our procedures may be applied to both single-cell and bulk RNA-seq. We show that our simulation method results in more realistic datasets and can alter the conclusions of a differential expression analysis study. We also demonstrate our approach by comparing various factor analysis techniques on RNA-seq datasets. CONCLUSIONS: Using data simulated from a theoretical model can substantially impact the results of a study. We developed more realistic simulation techniques for RNA-seq data. Our tools are available in the seqgendiff R package on the Comprehensive R Archive Network: https://cran.r-project.org/package=seqgendiff.


Assuntos
Simulação por Computador , Bases de Dados Genéticas , RNA-Seq , Algoritmos , Perfilação da Expressão Gênica , Humanos , Análise de Componente Principal , Software , Sequenciamento do Exoma
8.
J Clin Gastroenterol ; 51(6): 512-521, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27433812

RESUMO

BACKGROUND: We assessed the efficacy and tolerability of 5 low-volume bowel preparations for colonoscopy. STUDY: We performed an investigator-blinded, randomized trial of 5 bowel preparations: 64 ounces of Gatorade and 306 or 357 g of PEG, both given the day prior; Gatorade and 306 g PEG, 2 L PEG-electrolyte solution with ascorbic acid, and sulfate solution, all 3 given as a split dose. One thousand outpatients consumed their preparation before a morning colonoscopy. The primary endpoint was colon cleanliness assessed by the Chicago Bowel Preparation Scale (BPS). Tolerability was assessed using a subject questionnaire. Another primary endpoint was patient acceptance of a split-dose bowel preparation assessed using a subject questionnaire. RESULTS: No statistically significant differences in the modified Chicago BPS were found among Gatorade and 357 g of PEG given as a day-prior dose and the 3 split-dose arms with 98.5% of colons cleansed adequately. The Gatorade and 357 g of PEG had significantly lower Chicago BPS fluid scores and Chicago BPS total scores (indicating dryer colons that required more irrigation) than the 3 split-dose arms. The Gatorade and PEG preparations were better tolerated. Many subjects are unwilling to consume a split-dose preparation and the majority of subjects would prefer a day-prior preparation with this preference highly dependent on the type of preparation they just consumed. CONCLUSIONS: The cleanliness of the colons was not significantly different among the 3 split-dose preparations. Day-prior dosing of Gatorade and 357 g of PEG allowed the mucosa to be visualized as well as did the split-dose preparations.


Assuntos
Catárticos/administração & dosagem , Colonoscopia/métodos , Soluções Isotônicas/administração & dosagem , Polietilenoglicóis/administração & dosagem , Idoso , Catárticos/efeitos adversos , Eletrólitos/administração & dosagem , Eletrólitos/efeitos adversos , Feminino , Humanos , Soluções Isotônicas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Polietilenoglicóis/efeitos adversos , Estudos Prospectivos , Método Simples-Cego , Inquéritos e Questionários
9.
Nanomedicine ; 13(7): 2117-2126, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28579435

RESUMO

The potential of graphene-based nanoparticles (GNPs) has recently gained significant attention in biomedicine, especially in tissue engineering. In this study, we investigated the osteoinductive and osteoconductive effects of low oxygen content graphene (LOG) nanoparticles on adult mesenchymal stem cells (MSCs) in vitro and in vivo. We showed that adult goat MSCs were viable in the presence of 0.1 mg/mL LOG and retained their stem cell properties. A 3D scaffold made from agarose was used to encapsulate MSCs and LOG nanoparticles. Scanning electron microscopy demonstrated the cell morphology and adherence of MSCs to LOG in the 3D form. The LOG and MSCs in the 3D scaffold were xenogenically implanted into a rat unicortical tibial bone defect. The combination of MSCs and LOG nanoparticles resulted in improved active bone formation and increased mineralization. These results strengthen the applicability of LOG nanoparticles as an adjunct treatment for bone tissue engineering.


Assuntos
Regeneração Óssea , Grafite/química , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Nanopartículas/química , Alicerces Teciduais/química , Animais , Células Cultivadas , Cabras , Transplante de Células-Tronco Mesenquimais/métodos , Osteogênese , Ratos Sprague-Dawley
10.
J Oral Maxillofac Surg ; 72(1): 61-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23891015

RESUMO

PURPOSE: This study was conducted with 2 purposes. The first was to determine the effect of a single dose of zoledronic acid (ZA) on the healing of a tooth extraction socket in dogs. The second was to determine if placement of recombinant human bone morphogenetic protein-2 (rhBMP-2)/absorbable collagen sponge (ACS) - INFUSE, (Medtronic, Memphis, TN) into these extraction sockets would inhibit the inhibition on bone healing and remodeling by ZA. MATERIALS AND METHODS: Nine adult female beagle dogs (2 to 3 yr old) were placed into 3 groups of 3 dogs each. Group I received 15 mL of sterile saline intravenously; group II received 2.5 mg of ZA intravenously; and group III received 5 mg of ZA intravenously. Forty-five days after treatment, all dogs underwent extraction of noncontiguous right and left mandibular first molars and second premolars. In group I, the right mandibular extraction sockets had nothing placed in them, whereas the left mandibular sockets had only ACS placed in them. In groups II and III, the right mandibular sockets had rhBMP-2/ACS placed in them, whereas the left mandibular sockets had only ACS placed. All extraction sockets were surgically closed. Tetracycline was given intravenously 5 and 12 days later, and all animals were euthanized 15 days after tooth extraction. The extraction sockets and rib and femur samples were harvested immediately after euthanasia, processed, and studied microscopically. RESULTS: A single dose of ZA significantly inhibited healing and bone remodeling in the area of the tooth extractions. The combination of rhBMP-2/ACS appeared to over-ride some of the bone remodeling inhibition of the ZA and increased bone fill in the extraction sites, and remodeling activity in the area was noted. The effects of rhBMP-2/ACS were confined to the area of the extraction sockets because bone activity at distant sites was not influenced. CONCLUSIONS: A single dose of ZA administered intravenously inhibits early healing of tooth extraction sockets and bone remodeling in this animal model. The combination of rhBMP-2/ACS significantly increased bone fill and bone remodeling in these areas, negating much of the effect of the ZA.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Proteína Morfogenética Óssea 2/farmacologia , Difosfonatos/farmacologia , Imidazóis/farmacologia , Alvéolo Dental/efeitos dos fármacos , Fator de Crescimento Transformador beta/farmacologia , Animais , Antraquinonas , Dente Pré-Molar/cirurgia , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/antagonistas & inibidores , Remodelação Óssea/efeitos dos fármacos , Colágeno , Corantes , Difosfonatos/administração & dosagem , Difosfonatos/antagonistas & inibidores , Cães , Portadores de Fármacos , Feminino , Fêmur/efeitos dos fármacos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imidazóis/administração & dosagem , Imidazóis/antagonistas & inibidores , Injeções Intravenosas , Dente Molar/cirurgia , Osteogênese/efeitos dos fármacos , Proteínas Recombinantes/farmacologia , Costelas/efeitos dos fármacos , Cloreto de Tolônio , Extração Dentária , Cicatrização/efeitos dos fármacos , Ácido Zoledrônico
11.
Chimia (Aarau) ; 68(12): 893-5, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26508615

RESUMO

To celebrate the International Year of Crystallography among the general public, a consortium of chemists, physicists and crystallographers of the University of Geneva organised in Spring 2014 an incentive crystal growth contest for Geneva scholars aged 4 to 19. Starting from a kit containing a salt and user instructions, classes had to prepare a crystal that met specific criteria according to their category of age. The composition of the salt - potassium dihydrogen phosphate (KDP) - was only disclosed to the participants during the final Awards Ceremony. This contest positively exceeded our expectations with almost 100 participating classes (ca. 1800 participants) and 54 specimens received over all categories.

12.
Orig Life Evol Biosph ; 43(2): 161-87, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23715690

RESUMO

The distributions of amino acids at most-conserved sites nearest catalytic/active centers (C/AC) in 4,645 sequences of ten enzymes of the glycolytic Embden-Meyerhof-Parnas pathway in Archaea, Bacteria and Eukaryota are similar to the proposed temporal order of their appearance on Earth. Glycine, isoleucine, leucine, valine, glutamic acid and possibly lysine often described as prebiotic, i.e., existing or occurring before the emergence of life, were localized in positional and conservational defined aggregations in all enzymes of all Domains. The distributions of all 20 biologic amino acids in most-conserved sites nearest their C/ACs were quite different either from distributions in sites less-conserved and further from their C/ACs or from all amino acids regardless of their position or conservation. The major concentrations of glycine, e.g., perhaps the earliest prebiotic amino acid, occupies ≈ 16 % of all the most-conserved sites within a volume of ≈ 7-8 Å radius from their C/ACs and decreases linearly towards the molecule's peripheries. Spatially localized major concentrations of isoleucine, leucine and valine are in the mid-conserved and mid-distant sites from their C/ACs in protein interiors. Lysine and glutamic acid comprise ≈ 25-30 % of all amino acids within an irregular volume bounded by ≈ 24-28 Å radii from their C/ACs at the most-distant least-conserved sites. The unreported characteristics of these amino acids: their spatially and conservationally identified concentrations in Archaea, Bacteria and Eukaryota, suggest some common structural organization of glycolytic enzymes that may be relevant to their evolution and that of other proteins. We discuss our data in relation to enzyme evolution, their reported prebiotic putative temporal appearances on Earth, abundances, biological "cost", neighbor-sequence preferences or "ordering" and some thermodynamic parameters.


Assuntos
Aminoácidos/química , Archaea/enzimologia , Bactérias/enzimologia , Domínio Catalítico , Enzimas/química , Eucariotos/enzimologia , Evolução Molecular , Sequência de Aminoácidos , Aminoácidos/análise , Sequência Conservada , Planeta Terra , Enzimas/metabolismo , Isoleucina/análise , Leucina/análise , Modelos Logísticos , Dados de Sequência Molecular , Valina/análise
13.
Mol Ecol Resour ; 23(8): 1812-1822, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37578636

RESUMO

Hardy-Weinberg proportions (HWP) are often explored to evaluate the assumption of random mating. However, in autopolyploids, organisms with more than two sets of homologous chromosomes, HWP and random mating are different hypotheses that require different statistical testing approaches. Currently, the only available methods to test for random mating in autopolyploids (i) heavily rely on asymptotic approximations and (ii) assume genotypes are known, ignoring genotype uncertainty. Furthermore, these approaches are all frequentist, and so do not carry the benefits of Bayesian analysis, including ease of interpretability, incorporation of prior information, and consistency under the null. Here, we present Bayesian approaches to test for random mating, bringing the benefits of Bayesian analysis to this problem. Our Bayesian methods also (i) do not rely on asymptotic approximations, being appropriate for small sample sizes, and (ii) optionally account for genotype uncertainty via genotype likelihoods. We validate our methods in simulations and demonstrate on two real datasets how testing for random mating is more useful for detecting genotyping errors than testing for HWP (in a natural population) and testing for Mendelian segregation (in an experimental S1 population). Our methods are implemented in Version 2.0.2 of the hwep R package on the Comprehensive R Archive Network https://cran.r-project.org/package=hwep.


Assuntos
Modelos Genéticos , Poliploidia , Humanos , Frequência do Gene , Teorema de Bayes , Probabilidade , Genótipo
14.
Front Psychiatry ; 14: 1098224, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36873199

RESUMO

Background: Receiving the label of a psychotic disorder influences self-perception and may result in negative outcomes such as self-stigma and decreased self-esteem. The way the diagnosis is communicated to individuals may affect these outcomes. Aims: This study aims to explore the experiences and needs of individuals after a first episode of psychosis with regard to the way in which information about diagnosis, treatment options and prognosis is communicated with them. Design and methods: A descriptive interpretative phenomenological approach was used. Fifteen individuals who experienced a first episode of psychosis participated in individual semi-structured open-ended interviews on their experiences and needs regarding the process of providing information about diagnosis, treatment options and prognosis. Inductive thematic analysis was used to analyze the interviews. Results: Four recurring themes where identified (1) timing (when); (2) content (what); and (3) the way information is provided (how). Individuals also reported that the provided information could elicit an emotional reaction, for which they would require specific attention, therefore the fourth theme is (4) reactions and feelings. Conclusion: This study provides new insights into the experiences and specific information needed by individuals with a first episode of psychosis. Results suggest that individuals have different needs regarding the type of (what), how and when to receive information about diagnosis and treatment options. This requires a tailor-made process of communicating diagnosis. A guideline on when, how and what to inform, as well as providing personalized written information regarding the diagnosis and treatment options, is recommended.

15.
Cancers (Basel) ; 15(8)2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37190187

RESUMO

Due to poor compliance and uptake of LDCT screening among high-risk populations, lung cancer is often diagnosed in advanced stages where treatment is rarely curative. Based upon the American College of Radiology's Lung Imaging and Reporting Data System (Lung-RADS) 80-90% of patients screened will have clinically "non-actionable" nodules (Lung-RADS 1 or 2), and those harboring larger, clinically "actionable" nodules (Lung-RADS 3 or 4) have a significantly greater risk of lung cancer. The development of a companion diagnostic method capable of identifying patients likely to have a clinically actionable nodule identified during LDCT is anticipated to improve accessibility and uptake of the paradigm and improve early detection rates. Using protein microarrays, we identified 501 circulating targets with differential immunoreactivities against cohorts characterized as possessing either actionable (n = 42) or non-actionable (n = 20) solid pulmonary nodules, per Lung-RADS guidelines. Quantitative assays were assembled on the Luminex platform for the 26 most promising targets. These assays were used to measure serum autoantibody levels in 841 patients, consisting of benign (BN; n = 101), early-stage non-small cell lung cancer (NSCLC; n = 245), other early-stage malignancies within the lung (n = 29), and individuals meeting United States Preventative Screening Task Force (USPSTF) screening inclusion criteria with both actionable (n = 87) and non-actionable radiologic findings (n = 379). These 841 patients were randomly split into three cohorts: Training, Validation 1, and Validation 2. Of the 26 candidate biomarkers tested, 17 differentiated patients with actionable nodules from those with non-actionable nodules. A random forest model consisting of six autoantibody (Annexin 2, DCD, MID1IP1, PNMA1, TAF10, ZNF696) biomarkers was developed to optimize our classification performance; it possessed a positive predictive value (PPV) of 61.4%/61.0% and negative predictive value (NPV) of 95.7%/83.9% against Validation cohorts 1 and 2, respectively. This panel may improve patient selection methods for lung cancer screening, serving to greatly reduce the futile screening rate while also improving accessibility to the paradigm for underserved populations.

16.
J Vis Exp ; (180)2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-35253789

RESUMO

Multiplex technologies for interrogating multiple biomarkers in concert have existed for several decades; however, methods to evaluate multiple epitopes on the same analyte remain limited. This report describes the development and optimization of a multiplexed immunobead assay for serological testing of common immunoglobulin isotypes (e.g., IgA, IgM, and IgG) associated with an immune response to SARS-CoV-2 infection or vaccination. Assays were accomplished using a flow-based, multiplex fluorescent reader with dual-channel capability. Optimizations focused on analyte capture time, detection antibody concentration, and detection antibody incubation time. Analytical assay performance characteristics (e.g., assay range (including lower and upper limits of quantitation); and intra- and inter-assay precision) were established for either IgG/IgM or IgA/IgM serotype combination in tandem using the 'dual channel' mode. Analyte capture times of 30 min for IgG, 60 min for IgM, and 120 min for IgA were suitable for most applications, providing a balance of assay performance and throughput. Optimal detection antibody incubations at 4 µg/mL for 30 min was observed and are recommended for general applications, given the overall excellent precision (percent coefficient of variance (%CV) ≤ 20%) and sensitivity values observed. The dynamic range for the IgG isotype spanned several orders of magnitude for each assay (Spike S1, Nucleocapsid, and Membrane glycoproteins), which supports robust titer evaluations at a 1:500 dilution factor for clinical applications. Finally, the optimized protocol was applied to monitoring Spike S1 seroconversion for subjects (n = 4) that completed a SARS-CoV-2 vaccine regimen. Within this cohort, Spike S1 IgG levels were observed to reach maximum titers at 14 days following second dose administration, at a much higher (~40-fold) signal intensity than either IgM or IgA isotypes. Interestingly, we observed highly variable Spike S1 IgG titer decay rates that were largely subject-dependent were observed, which will be the topic of future studies.


Assuntos
COVID-19 , Anticorpos Antivirais , COVID-19/diagnóstico , Vacinas contra COVID-19 , Humanos , Imunoglobulina G , Imunoglobulina M , SARS-CoV-2 , Sensibilidade e Especificidade , Soroconversão , Glicoproteína da Espícula de Coronavírus
17.
Oncotarget ; 13: 393-407, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35198099

RESUMO

BACKGROUND: Detection rates of early-stage lung cancer are traditionally low, which contributes to inconsistent treatment responses and high rates of annual cancer deaths. Currently, low-dose computed tomography (LDCT) screening produces a high false discovery rate. This limitation has prompted research to identify biomarkers to more clearly define eligible patients for LDCT screening, differentiate indeterminate pulmonary nodules, and select individualized cancer therapy. Biomarkers within the Insulin-like Growth Factor (IGF) family have come to the forefront of this research. Main Body: Multiple biomarkers within the IGF family have been investigated, most notably IGF-I and IGF binding protein 3. However, newer studies seek to expand this search to other molecules within the IGF axis. Certain studies have demonstrated these biomarkers are useful when used in combination with lung cancer screening, but other findings were not as conclusive, possibly owing to measurement bias and non-standardized assay techniques. Research also has suggested IGF biomarkers may be beneficial in the prognostication and subsequent treatment via systemic therapy. Despite these advances, additional knowledge of complex regulatory mechanisms inherent to this system are necessary to more fully harness the potential clinical utility for diagnostic and therapeutic purposes. CONCLUSIONS: The IGF system likely plays a role in multiple phases of lung cancer; however, there is a surplus of conflicting data, especially prior to development of the disease and during early stages of detection. IGF biomarkers may be valuable in the screening, prognosis, and treatment of lung cancer, though their exact application requires further study.


Assuntos
Neoplasias Pulmonares , Biomarcadores Tumorais , Detecção Precoce de Câncer/métodos , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina , Fator de Crescimento Insulin-Like I , Neoplasias Pulmonares/diagnóstico , Programas de Rastreamento/métodos , Prognóstico
18.
Soft Robot ; 9(3): 497-508, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34107745

RESUMO

Soft gripping provides the potential for high performance in challenging tasks through morphological computing; however, design explorations are limited by a combination of a difficulty in generating useful models and use of laborious fabrication techniques. We focus on a class of grippers based on granular jamming that are particularly difficult to model and introduce a "one shot" technique that exploits multimaterial three-dimensional (3D) printing to create entire grippers, including membrane and grains, in a single print run. This technique fully supports the de facto physical generate-and-test methodology used for this class of grippers, as entire design iterations can be fitted onto a single print bed and fabricated from Computer-Aided Design (CAD) files in a matter of hours. Initial results demonstrate the approach by rapidly prototyping in materio solutions for two challenging problems in unconventional design spaces; a twisting gripper that uses programmed deformations to reliably pick a coin, and a multifunctional legged robot paw that offers the ability for compliant locomotion over rough terrains, as well as being able to pick objects in cluttered natural environments. The technique also allows us to easily characterize the design space of multimaterial printed jamming grippers and provide some useful design rules. The simplicity of our technique encourages and facilitates creativity and innovation. As such, we see our approach as an enabling tool to make informed principled forays into unconventional design spaces and support the creation of a new breed of novel soft actuators.


Assuntos
Robótica , Desenho Assistido por Computador , Desenho de Equipamento , Força da Mão , Impressão Tridimensional , Robótica/métodos
19.
BMC Evol Biol ; 11: 291, 2011 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-21978073

RESUMO

BACKGROUND: A well-known characteristic of multi-locus data is that each locus has its own phylogenetic history which may differ substantially from the overall phylogenetic history of the species. Although the possibility that this arises through incomplete lineage sorting is often incorporated in models for the species-level phylogeny, it is much less common for hybridization to also be formally included in such models. RESULTS: We have modified the evolutionary model of Meng and Kubatko (2009) to incorporate intraspecific sampling of multiple individuals for estimation of speciation times and times of hybridization events for testing for hybridization in the presence of incomplete lineage sorting. We have also utilized a more efficient algorithm for obtaining our estimates. Using simulations, we demonstrate that our approach performs well under conditions motivated by an empirical data set for Sistrurus rattlesnakes where putative hybridization has occurred. We further demonstrate that the method is able to accurately detect the signature of hybridization in the data, while this signal may be obscured when other species-tree inference methods that ignore hybridization are used. CONCLUSIONS: Our approach is shown to be powerful in detecting hybridization when it is present. When applied to the Sistrurus data, we find no evidence of hybridization; instead, it appears that putative hybrid snakes in Missouri are most likely pure S. catenatus tergeminus in origin, which has significant conservation implications.


Assuntos
Algoritmos , Hibridização Genética , Modelos Genéticos , Filogenia , Serpentes/genética , Animais , Simulação por Computador , Especiação Genética , Missouri
20.
Mol Ecol Resour ; 21(4): 1230-1242, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33559321

RESUMO

Many tasks in statistical genetics involve pairwise estimation of linkage disequilibrium (LD). The study of LD in diploids is mature. However, in polyploids, the field lacks a comprehensive characterization of LD. Polyploids also exhibit greater levels of genotype uncertainty than diploids, yet no methods currently exist to estimate LD in polyploids in the presence of such genotype uncertainty. Furthermore, most LD estimation methods do not quantify the level of uncertainty in their LD estimates. Our study contains three major contributions. (i) We characterize haplotypic and composite measures of LD in polyploids. These composite measures of LD turn out to be functions of common statistical measures of association. (ii) We derive procedures to estimate haplotypic and composite LD in polyploids in the presence of genotype uncertainty. We do this by estimating LD directly from genotype likelihoods, which may be obtained from many genotyping platforms. (iii) We derive standard errors of all LD estimators that we discuss. We validate our methods on both real and simulated data. Our methods are implemented in the R package ldsep, available on the Comprehensive R Archive Network https://cran.r-project.org/package=ldsep.


Assuntos
Desequilíbrio de Ligação , Modelos Genéticos , Poliploidia , Software , Genótipo , Haplótipos , Modelos Estatísticos , Polimorfismo de Nucleotídeo Único
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