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1.
Science ; 384(6691): 48-53, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38574139

RESUMO

Understanding universal aspects of quantum dynamics is an unresolved problem in statistical mechanics. In particular, the spin dynamics of the one-dimensional Heisenberg model were conjectured as to belong to the Kardar-Parisi-Zhang (KPZ) universality class based on the scaling of the infinite-temperature spin-spin correlation function. In a chain of 46 superconducting qubits, we studied the probability distribution of the magnetization transferred across the chain's center, [Formula: see text]. The first two moments of [Formula: see text] show superdiffusive behavior, a hallmark of KPZ universality. However, the third and fourth moments ruled out the KPZ conjecture and allow for evaluating other theories. Our results highlight the importance of studying higher moments in determining dynamic universality classes and provide insights into universal behavior in quantum systems.

2.
Science ; 383(6689): 1332-1337, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38513021

RESUMO

Engineered dissipative reservoirs have the potential to steer many-body quantum systems toward correlated steady states useful for quantum simulation of high-temperature superconductivity or quantum magnetism. Using up to 49 superconducting qubits, we prepared low-energy states of the transverse-field Ising model through coupling to dissipative auxiliary qubits. In one dimension, we observed long-range quantum correlations and a ground-state fidelity of 0.86 for 18 qubits at the critical point. In two dimensions, we found mutual information that extends beyond nearest neighbors. Lastly, by coupling the system to auxiliaries emulating reservoirs with different chemical potentials, we explored transport in the quantum Heisenberg model. Our results establish engineered dissipation as a scalable alternative to unitary evolution for preparing entangled many-body states on noisy quantum processors.

3.
Nature ; 612(7939): 240-245, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36477133

RESUMO

Systems of correlated particles appear in many fields of modern science and represent some of the most intractable computational problems in nature. The computational challenge in these systems arises when interactions become comparable to other energy scales, which makes the state of each particle depend on all other particles1. The lack of general solutions for the three-body problem and acceptable theory for strongly correlated electrons shows that our understanding of correlated systems fades when the particle number or the interaction strength increases. One of the hallmarks of interacting systems is the formation of multiparticle bound states2-9. Here we develop a high-fidelity parameterizable fSim gate and implement the periodic quantum circuit of the spin-½ XXZ model in a ring of 24 superconducting qubits. We study the propagation of these excitations and observe their bound nature for up to five photons. We devise a phase-sensitive method for constructing the few-body spectrum of the bound states and extract their pseudo-charge by introducing a synthetic flux. By introducing interactions between the ring and additional qubits, we observe an unexpected resilience of the bound states to integrability breaking. This finding goes against the idea that bound states in non-integrable systems are unstable when their energies overlap with the continuum spectrum. Our work provides experimental evidence for bound states of interacting photons and discovers their stability beyond the integrability limit.

4.
Science ; 378(6621): 785-790, 2022 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-36395220

RESUMO

Inherent symmetry of a quantum system may protect its otherwise fragile states. Leveraging such protection requires testing its robustness against uncontrolled environmental interactions. Using 47 superconducting qubits, we implement the one-dimensional kicked Ising model, which exhibits nonlocal Majorana edge modes (MEMs) with [Formula: see text] parity symmetry. We find that any multiqubit Pauli operator overlapping with the MEMs exhibits a uniform late-time decay rate comparable to single-qubit relaxation rates, irrespective of its size or composition. This characteristic allows us to accurately reconstruct the exponentially localized spatial profiles of the MEMs. Furthermore, the MEMs are found to be resilient against certain symmetry-breaking noise owing to a prethermalization mechanism. Our work elucidates the complex interplay between noise and symmetry-protected edge modes in a solid-state environment.

5.
Placenta ; 121: 99-108, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35305398

RESUMO

Epidemiological studies have associated ambient engineered nanomaterials or ultrafine particulate matter (PM0.1), collectively referred to as nanoparticles (NPs), with adverse pregnancy outcomes including miscarriage, preterm labor, and fetal growth restriction. Evidence from non-pregnant models demonstrate that NPs can cross the lung air-blood barrier and circulate systemically. Therefore, inhalation of NPs during pregnancy leading to fetoplacental exposure has garnered attention. The purpose of this study was to evaluate the distribution of inhaled titanium dioxide nanoparticles (nano-TiO2) from the maternal lung to maternal and fetal systemic tissues. Pregnant Sprague Dawley rats were administered whole-body exposure to filtered air or of nano-TiO2 aerosols (9.96 ± 0.06 mg/m3) between gestational day (GD) 4 and 19. On GD 20 maternal, placental, and fetal tissues were harvested then digested for ICP-MS analysis to measure concentrations of titanium (Ti). TEM was used to visualize particle internalization by the placental syncytium. The results demonstrate the extrapulmonary distribution of Ti to various maternal organs during pregnancy. Our study found Ti accumulation in the decidua/junctional and labyrinth zones of placentas embedded in all sections of uterine horns. Further, NPs deposited in the placenta, identified by TEM, were found intracellularly within nuclear, endoplasmic reticulum, and vesicle organelles. This study identified the systemic distribution and placental accumulation of Ti after nano-TiO2 aerosol inhalation in a pregnancy model. These findings arouse concerns for poor air quality for pregnant women and possible contributions to adverse pregnancy outcomes.


Assuntos
Aborto Espontâneo , Nanopartículas , Animais , Feminino , Feto , Exposição Materna/efeitos adversos , Nanopartículas/efeitos adversos , Placenta , Gravidez , Ratos , Ratos Sprague-Dawley , Titânio/efeitos adversos
6.
Science ; 374(6572): 1237-1241, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34855491

RESUMO

The discovery of topological order has revised the understanding of quantum matter and provided the theoretical foundation for many quantum error­correcting codes. Realizing topologically ordered states has proven to be challenging in both condensed matter and synthetic quantum systems. We prepared the ground state of the toric code Hamiltonian using an efficient quantum circuit on a superconducting quantum processor. We measured a topological entanglement entropy near the expected value of ­ln2 and simulated anyon interferometry to extract the braiding statistics of the emergent excitations. Furthermore, we investigated key aspects of the surface code, including logical state injection and the decay of the nonlocal order parameter. Our results demonstrate the potential for quantum processors to provide insights into topological quantum matter and quantum error correction.

7.
J Bacteriol ; 203(22): e0036721, 2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34516280

RESUMO

The bacterial flagellar motor (BFM) is a protein complex that confers motility to cells and contributes to survival and virulence. The BFM consists of stators that are ion-selective membrane protein complexes and a rotor that directly connects to a large filament, acting as a propeller. The stator complexes couple ion transit across the membrane to torque that drives rotation of the motor. The most common ion gradients that drive BFM rotation are protons (H+) and sodium ions (Na+). The sodium-powered stators, like those in the PomA/PomB stator complex of Vibrio spp., can be inhibited by sodium channel inhibitors, in particular, by phenamil, a potent and widely used inhibitor. However, relatively few new sodium motility inhibitors have been described since the discovery of phenamil. In this study, we characterized two possible motility inhibitors, HM2-16F and BB2-50F, from a small library of previously reported amiloride derivatives. We used three approaches: effect on rotation of tethered cells, effect on free-swimming bacteria, and effect on rotation of marker beads. We showed that both HM2-16F and BB2-50F stopped rotation of tethered cells driven by Na+ motors comparable to phenamil at matching concentrations and could also stop rotation of tethered cells driven by H+ motors. Bead measurements in the presence and absence of stators confirmed that the compounds did not inhibit rotation via direct association with the stator, in contrast to the established mode of action of phenamil. Overall, HM2-16F and BB2-50F stopped swimming in both Na+ and H+ stator types and in pathogenic and nonpathogenic strains. IMPORTANCE Here, we characterized two novel amiloride derivatives in the search for antimicrobial compounds that target bacterial motility. These compounds were shown to inhibit flagellar motility at 10 µM across multiple strains: from nonpathogenic Escherichia coli with flagellar rotation driven by proton or chimeric sodium-powered stators, to proton-powered pathogenic E. coli (enterohemorrhagic E. coli or uropathogenic E. coli [EHEC or UPEC, respectively]), and finally, sodium-powered Vibrio alginolyticus. Broad antimotility compounds such as these are important tools in our efforts to control virulence of pathogens in health and agricultural settings.


Assuntos
Amilorida/análogos & derivados , Amilorida/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Vibrio alginolyticus/efeitos dos fármacos , Vibrio alginolyticus/fisiologia , Bloqueadores do Canal Iônico Sensível a Ácido/farmacologia , Amilorida/química , Escherichia coli/classificação , Movimento
8.
Appl Physiol Nutr Metab ; 46(11): 1430-1434, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34324824

RESUMO

Despite widespread use, community-based physical activity prescription is controversial. Data limitations have resulted in a lack of clarity about what works, under what circumstances, and for whom, reflected in conservative policy recommendations. In this commentary we challenge a predominantly negative discourse, using contemporary research to highlight promising findings and "lessons learnt" for design, delivery, and evaluation. In doing so, we argue for the importance of a more nuanced approach to future commissioning and evaluation. Novelty: Amalgamating learning from multiple research teams to create recommendations for advancing physical activity prescription.


Assuntos
Projetos de Pesquisa Epidemiológica , Exercício Físico , Promoção da Saúde , Humanos , Reino Unido
9.
Clin Radiol ; 76(9): 640-649, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34108098

RESUMO

Scleroderma is a complex multisystem connective tissue disorder. Early visceral disease, such as gastrointestinal (GI) involvement, is associated with significant morbidity and a poorer prognosis. Prompt diagnosis is crucial to allow disease modifying therapies be initiated early in the course of the disease. The primary underlying pathophysiology in the GI tract is dysmotility, muscular atrophy, and fibrosis, and this is reflected in the imaging features. In this paper, we demonstrate the imaging appearances of involvement of the GI tract and describe the use of advanced imaging with magnetic resonance enterography (MRE). A multimodal imaging approach is required to identify both characteristic features of scleroderma and potential complications. Traditional fluoroscopic contrast (barium) studies are still commonly performed for assessment of the oesophagus. More recent advances in cross-sectional imaging allow for thorough three-dimensional assessment of the entire GI tract. MRE is particularly useful for small bowel evaluation while also allowing "pseudodynamic" functional imaging and concomitant assessment of the other abdominal viscera and structures.


Assuntos
Gastroenteropatias/diagnóstico por imagem , Gastroenteropatias/etiologia , Imageamento por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Escleroderma Sistêmico/complicações , Tomografia Computadorizada por Raios X/métodos , Trato Gastrointestinal/diagnóstico por imagem , Humanos
10.
Nature ; 594(7864): 508-512, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34163052

RESUMO

A promising approach to study condensed-matter systems is to simulate them on an engineered quantum platform1-4. However, the accuracy needed to outperform classical methods has not been achieved so far. Here, using 18 superconducting qubits, we provide an experimental blueprint for an accurate condensed-matter simulator and demonstrate how to investigate fundamental electronic properties. We benchmark the underlying method by reconstructing the single-particle band structure of a one-dimensional wire. We demonstrate nearly complete mitigation of decoherence and readout errors, and measure the energy eigenvalues of this wire with an error of approximately 0.01 rad, whereas typical energy scales are of the order of 1 rad. Insight into the fidelity of this algorithm is gained by highlighting the robust properties of a Fourier transform, including the ability to resolve eigenenergies with a statistical uncertainty of 10-4 rad. We also synthesize magnetic flux and disordered local potentials, which are two key tenets of a condensed-matter system. When sweeping the magnetic flux we observe avoided level crossings in the spectrum, providing a detailed fingerprint of the spatial distribution of local disorder. By combining these methods we reconstruct electronic properties of the eigenstates, observing persistent currents and a strong suppression of conductance with added disorder. Our work describes an accurate method for quantum simulation5,6 and paves the way to study new quantum materials with superconducting qubits.

11.
Nat Commun ; 12(1): 1761, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741936

RESUMO

Quantum computing can become scalable through error correction, but logical error rates only decrease with system size when physical errors are sufficiently uncorrelated. During computation, unused high energy levels of the qubits can become excited, creating leakage states that are long-lived and mobile. Particularly for superconducting transmon qubits, this leakage opens a path to errors that are correlated in space and time. Here, we report a reset protocol that returns a qubit to the ground state from all relevant higher level states. We test its performance with the bit-flip stabilizer code, a simplified version of the surface code for quantum error correction. We investigate the accumulation and dynamics of leakage during error correction. Using this protocol, we find lower rates of logical errors and an improved scaling and stability of error suppression with increasing qubit number. This demonstration provides a key step on the path towards scalable quantum computing.

12.
Clin Microbiol Infect ; 25(10): 1213-1225, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31284031

RESUMO

BACKGROUND: Vaccines may reduce antibiotic use and the development of resistance. OBJECTIVES: To provide a comprehensive, up-to-date assessment of the evidence base relating to the effect of vaccines on antibiotic use. DATA SOURCES: Ovid MEDLINE, Embase, the Cochrane Library, ClinicalTrials.gov and WHO Trials Registry. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) and observational studies published from January 1998 to March 2018. PARTICIPANTS: Any population. INTERVENTIONS: Vaccines versus placebo, no vaccine or another vaccine. METHODS: Titles, abstracts and full-texts were screened independently by two reviewers. Certainty of RCT evidence was assessed using GRADE. RESULTS: In all, 4980 records identified; 895 full-text reports assessed; 96 studies included (24 RCTs, 72 observational). There was high-certainty evidence that influenza vaccine reduces days of antibiotic use among healthy adults (one RCT; n = 4253; rate reduction 28·1%; 95% CI 16·0-38·4); moderate-certainty evidence that influenza vaccines probably reduce antibiotic use in children aged 6 months to 14 years (three RCTs; n = 610; ratio of means 0·62; 95% CI 0·54-0·70) and probably reduce community antibiotic use in children aged 3-15 years (one RCT; n = 10 985 person-seasons; risk ratio 0·69, 95% CI 0·58-0·83); and moderate-certainty evidence that pneumococcal vaccination probably reduces antibiotic use in children aged 6 weeks to 6 years (two RCTs; n = 47 945; rate ratio 0·93, 95% CI 0·87-0·99) and reduces illness episodes requiring antibiotics in children aged 12-35 months (one RCT; n = 264; rate ratio 0·85, 95% CI 0·75-0·97). Other RCT evidence was of low or very low certainty, and observational evidence was affected by confounding. CONCLUSIONS: The evidence base is poor. Although some vaccines may reduce antibiotic use, collection of high-quality data in future vaccine trials is needed to improve the evidence base. PROSPERO REGISTRATION: CRD42018103881.


Assuntos
Antibacterianos/uso terapêutico , Uso de Medicamentos/estatística & dados numéricos , Vacinação/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Saúde Global , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
13.
Biomed Pharmacother ; 117: 109148, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31347503

RESUMO

Development and implementation of products incorporating nanoparticles are occurring at a rapid pace. These particles are widely utilized in domestic, occupational, and biomedical applications. Currently, it is unclear if pregnant women will be able to take advantage of the potential biomedical nanoproducts out of concerns associated with placental transfer and fetal interactions. We recently developed an ex vivo rat placental perfusion technique to allow for the evaluation of xenobiotic transfer and placental physiological perturbations. In this study, a segment of the uterine horn and associated placenta was isolated from pregnant (gestational day 20) Sprague-Dawley rats and placed into a modified pressure myography vessel chamber. The proximal and distal ends of the maternal uterine artery and the vessels of the umbilical cord were cannulated, secured, and perfused with physiological salt solution (PSS). The proximal uterine artery and umbilical artery were pressurized at 80 mmHg and 50 mmHg, respectively, to allow countercurrent flow through the placenta. After equilibration, a single 900 µL bolus dose of 20 nm gold engineered nanoparticles (Au-ENM) was introduced into the proximal maternal artery. Distal uterine and umbilical vein effluents were collected every 10 min for 180 min to measure placental fluid dynamics. The quantification of Au-ENM transfer was conducted via inductively coupled plasma mass spectrometry (ICP-MS). Overall, we were able to measure Au-ENM within uterine and umbilical effluent with 20 min of material infusion. This novel methodology may be widely incorporated into studies of pharmacology, toxicology, and placental physiology.


Assuntos
Ouro/farmacologia , Nanoestruturas/química , Perfusão , Placenta/metabolismo , Animais , Feminino , Placenta/anatomia & histologia , Placenta/efeitos dos fármacos , Gravidez , Ratos Sprague-Dawley
14.
Food Chem Toxicol ; 116(Pt B): 227-232, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29678722

RESUMO

The environmental estrogen, zearalenone (ZEA), is found in the food supply from Fusarium fungal contamination in grains and sometimes used as a growth promoter for beef cattle. Long-term exposure to ZEA and its metabolites may present health risk due to higher estrogenic activity. Serum ZEA metabolites were measured to determine the exposure and the association with food intake in 48 overweight/obese women (52 ±â€¯9 years). The free and conjugated ZEA indicated the highest detection rate of all the metabolites. Conjugated ZEA and total ZEA metabolites were lower (p = 0.02) in overweight/obese than normal weight women, and free metabolites were either the same or showed a trend to be higher. In addition, those with highest (280-480 g/d) compared those with lowest (<115 g/d) meat consumption had higher conjugated serum ZEA metabolite concentrations (p < 0.05). Intakes of other food groups (i.e., dairy, cereal, etc.) were not associated with ZEA metabolites. These findings indicate that ZEA and its metabolites are detectable in nearly all women and concentrations are associated with greater meat intake, and influenced by body mass index. Determining how the food supply influences human concentrations of ZEA metabolites is warranted, as well as determining vulnerable populations.


Assuntos
Índice de Massa Corporal , Ingestão de Energia , Estrogênios não Esteroides/sangue , Zearalenona/sangue , Adulto , Cromatografia Líquida , Dieta , Estrogênios não Esteroides/metabolismo , Feminino , Abastecimento de Alimentos , Humanos , Limite de Detecção , Produtos da Carne , Menopausa , Pessoa de Meia-Idade , Obesidade/metabolismo , Sobrepeso/metabolismo , Espectrometria de Massas em Tandem , Zearalenona/metabolismo
15.
J Public Health (Oxf) ; 40(4): e586-e593, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29688551

RESUMO

Background: Translational research is required to ensure exercise referral schemes (ERSs) are evidence-based and reflect local needs. This article reports process data from the co-development phase of an ERS, providing an insight into (i) factors that must be considered when translating evidence to practice in an ERS setting, and (ii) challenges and facilitators of conducting participatory research involving multiple stakeholders. Methods: An ERS was iteratively co-developed by a multidisciplinary stakeholder group (commissioners, managers, practitioners, patients and academics) via five participatory meetings and an online survey. Audio data (e.g. group discussions) and visual data (e.g. whiteboard notes) were recorded and analysed using NVivo-10 electronic software. Results: Factors to consider when translating evidence to practice in an ERS setting included (i) current ERS culture; (ii) skills, safety and accountability; and (iii) resources and capacity. The co-development process was facilitated by needs-analysis, open questions, multidisciplinary debate and reflective practice. Challenges included contrasting views, irregular attendance and (mis)perceptions of evaluation. Conclusion: The multidisciplinary co-development process highlighted cultural and pragmatic issues related to exercise referral provision, resulting in an evidence-based intervention framework designed to be implemented within existing infrastructures. Further work is required to establish the feasibility and effectiveness of the co-developed intervention in practice.


Assuntos
Exercício Físico , Encaminhamento e Consulta/organização & administração , Pesquisa Participativa Baseada na Comunidade , Humanos , Avaliação das Necessidades , Desenvolvimento de Programas , Inquéritos e Questionários , Pesquisa Translacional Biomédica
16.
Phys Chem Chem Phys ; 20(17): 12037-12042, 2018 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-29671846

RESUMO

Non-equilibrium radio-frequency driven atmospheric-pressure plasma in He/0.6%O2 gas mixture has been used to study the reaction mechanism of plasma-generated oxygen atoms in aqueous solutions. The effluent from the plasma source operated with standard and 18O-labeled O2 gas was used to treat water in the presence of phenol as a chemical probe. Comparing the mass spectrometry and gas chromatography-mass spectrometry data of the solutions treated with plasma under normal and labeled oxygen provides clear evidence that O(aq) originating from the gas phase enters the liquid and reacts directly with phenol, without any intermediate reactions. Additionally, the atmospheric-pressure plasma source demonstrates great potential to be an effective source of O(aq) atoms without the requirement for any precursors in the liquid phase.

17.
Haemophilia ; 24(3): e93-e102, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29577531

RESUMO

INTRODUCTION: Central venous access devices (CVADs) facilitate repeated or urgent treatments for paediatric haemophilia patients, but are associated with complications. This study examined the burden of illness, healthcare utilization and costs for CVADs in a real-world hospital setting. MATERIALS AND METHODS: This study included haemophilia patients ages ≤18 years with discharges during 2006-2014 in the US Premier Healthcare Database. Haemophilia was identified using ICD-9 diagnosis codes and CVAD exposure using billing information. After matching haemophilia patients with and without CVADs on demographic and clinical characteristics, we compared infection, thrombosis, length of stay (LOS), inflation-adjusted hospital cost (2014 $USD) and readmission outcomes using generalized estimating equation models adjusted for hospital teaching status. RESULTS: Among 4793 paediatric haemophilia patients treated at one of 548 hospitals, a total of 197 patients were identified with CVAD exposure. The matched sample included 310 haemophilia patients (155 CVAD and 155 non-CVAD). CVAD cases had greater frequencies of all-cause infections (29% vs 17%, P = .01) and thrombosis (6% vs 1%, P = .06), longer adjusted mean LOS (9.5 vs 4.7 days, P = .002), higher adjusted mean inpatient total hospitalization costs ($47200 vs $25389, P = .02) as well as more inpatient and outpatient visits at 30-, 60- and 90-days (P < .05 for all differences) compared with non-CVAD patients. CONCLUSION: Paediatric haemophilia patients with CVADs experienced greater infection rates, healthcare utilization and higher hospitalization costs compared with non-CVAD patients. The results of this study may inform further research efforts to understand the costs and benefits of novel treatment alternatives for young haemophilia patients requiring CVADs.


Assuntos
Cateteres Venosos Centrais , Efeitos Psicossociais da Doença , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Hemofilia A/economia , Hemofilia A/terapia , Hospitais , Adolescente , Criança , Pré-Escolar , Feminino , Hemofilia A/complicações , Humanos , Lactente , Recém-Nascido , Infecções/complicações , Tempo de Internação , Masculino , Pacientes Ambulatoriais , Estudos Retrospectivos , Trombose/complicações , Estados Unidos
18.
J Anim Sci ; 96(3): 846-853, 2018 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-29471369

RESUMO

Reproductive performance is the most important component of cattle production from the standpoint of economic sustainability of commercial beef enterprises. Heifer Pregnancy (HPG) and Stayability (STAY) genetic predictions are 2 selection tools published by the Red Angus Association of America (RAAA) to assist with improvements in reproductive performance. Given the importance of HPG and STAY to the profitability of commercial beef enterprises, the objective of this study was to identify QTL associated with both HPG and STAY in Red Angus cattle. A genome-wide association study (GWAS) was performed using deregressed HPG and STAY EBV, calculated using a single-trait animal model and a 3-generation pedigree with data from the Spring 2015 RAAA National Cattle Evaluation. Each individual animal possessed 74,659 SNP genotypes. Individual animals with a deregressed EBV reliability > 0.05 were merged with the genotype file and marker quality control was performed. Criteria for sifting genotypes consisted of removing those markers where any of the following were found: average call rate less than 0.85, minor allele frequency < 0.01, lack of Hardy-Weinberg equilibrium (P < 0.0001), or extreme linkage disequilibrium (r2 > 0.99). These criteria resulted in 2,664 animals with 62,807 SNP available for GWAS. Association studies were performed using a Bayes Cπ model in the BOLT software package. Marker significance was calculated as the posterior probability of inclusion (PPI), or the number of instances a specific marker was sampled divided by the total number of samples retained from the Markov chain Monte Carlo chains. Nine markers, with a PPI ≥ 3% were identified as QTL associated with HPG on BTA 1, 11, 13, 23, and 29. Twelve markers, with a PPI ≥ 75% were identified as QTL associated with STAY on BTA 6, 8, 9, 12, 15, 18, 22, and 23.


Assuntos
Bovinos/genética , Estudo de Associação Genômica Ampla/veterinária , Locos de Características Quantitativas/genética , Reprodução/genética , Animais , Teorema de Bayes , Bovinos/fisiologia , Feminino , Frequência do Gene , Genótipo , Desequilíbrio de Ligação , Cadeias de Markov , Linhagem , Fenótipo , Gravidez , Reprodutibilidade dos Testes
19.
Pharmacogenomics J ; 18(2): 215-226, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28719597

RESUMO

Thiazide diuretics, commonly used antihypertensives, may cause QT interval (QT) prolongation, a risk factor for highly fatal and difficult to predict ventricular arrhythmias. We examined whether common single-nucleotide polymorphisms (SNPs) modified the association between thiazide use and QT or its component parts (QRS interval, JT interval) by performing ancestry-specific, trans-ethnic and cross-phenotype genome-wide analyses of European (66%), African American (15%) and Hispanic (19%) populations (N=78 199), leveraging longitudinal data, incorporating corrected standard errors to account for underestimation of interaction estimate variances and evaluating evidence for pathway enrichment. Although no loci achieved genome-wide significance (P<5 × 10-8), we found suggestive evidence (P<5 × 10-6) for SNPs modifying the thiazide-QT association at 22 loci, including ion transport loci (for example, NELL1, KCNQ3). The biologic plausibility of our suggestive results and simulations demonstrating modest power to detect interaction effects at genome-wide significant levels indicate that larger studies and innovative statistical methods are warranted in future efforts evaluating thiazide-SNP interactions.


Assuntos
Envelhecimento/genética , Etnicidade/genética , Genômica/tendências , Frequência Cardíaca/genética , Farmacogenética/tendências , Inibidores de Simportadores de Cloreto de Sódio/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/efeitos dos fármacos , Envelhecimento/etnologia , Estudos de Coortes , Eletrocardiografia/efeitos dos fármacos , Eletrocardiografia/tendências , Feminino , Genômica/métodos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Farmacogenética/métodos , Polimorfismo de Nucleotídeo Único/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único/genética
20.
Geophys Res Lett ; 44(10): 5104-5112, 2017 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-29950746

RESUMO

Volcanic eruptions have global climate impacts, but their effect on the hydrologic cycle is poorly understood. We use a modified version of superposed epoch analysis, an eruption year list collated from multiple datasets, and seasonal paleoclimate reconstructions (soil moisture, precipitation, geopotential heights, and temperature) to investigate volcanic forcing of spring and summer hydroclimate over Europe and the Mediterranean over the last millennium. In the western Mediterranean, wet conditions occur in the eruption year and the following 3 years. Conversely, northwestern Europe and the British Isles experience dry conditions in response to volcanic eruptions, with the largest moisture deficits in post-eruption years 2 and 3. The precipitation response occurs primarily in late spring and early summer (April-July), a pattern that strongly resembles the negative phase of the East Atlantic Pattern. Modulated by this mode of climate variability, eruptions force significant, widespread, and heterogeneous hydroclimate responses across Europe and the Mediterranean.

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