The accurate computation of Hamiltonian ground, excited and thermal states on quantum computers stands to impact many problems in the physical and computer sciences, from quantum simulation to ...machine learning. Given the challenges posed in constructing large-scale quantum computers, these tasks should be carried out in a resource-efficient way. In this regard, existing techniques based on phase estimation or variational algorithms display potential disadvantages; phase estimation requires deep circuits with ancillae, that are hard to execute reliably without error correction, while variational algorithms, while flexible with respect to circuit depth, entail additional high-dimensional classical optimization. Here, we introduce the quantum imaginary time evolution and quantum Lanczos algorithms, which are analogues of classical algorithms for finding ground and excited states. Compared with their classical counterparts, they require exponentially less space and time per iteration, and can be implemented without deep circuits and ancillae, or high-dimensional optimization. We furthermore discuss quantum imaginary time evolution as a subroutine to generate Gibbs averages through an analogue of minimally entangled typical thermal states. Finally, we demonstrate the potential of these algorithms via an implementation using exact classical emulation as well as through prototype circuits on the Rigetti quantum virtual machine and Aspen-1 quantum processing unit.The quantum imaginary time evolution and Lanczos algorithms offer a resource-efficient way to compute ground or excited states of target Hamiltonians on quantum computers. This offers promise for quantum simulation on near-term noisy devices.
"The upshot of this widespread failure to recognize that AIDS is an exceptional crisis and threat is that the response to the pandemic is not made commensurate to the challenges-and so the epidemic ...escalates even while it erodes our capacities to check it."
Copper is an essential trace element, but can become toxic when present in abundance. The severe effects of copper-metabolism imbalance are illustrated by the inherited disorders Wilson disease and ...Menkes disease. The Labrador retriever dog breed is a novel non-rodent model for copper-storage disorders carrying mutations in genes known to be involved in copper transport. Besides disease initiation and progression of copper accumulation, the molecular mechanisms and pathways involved in progression towards copper-associated chronic hepatitis still remain unclear. Using expression levels of targeted candidate genes as well as transcriptome micro-arrays in liver tissue of Labrador retrievers in different stages of copper-associated hepatitis, pathways involved in progression of the disease were studied. At the initial phase of increased hepatic copper levels, transcriptomic alterations in livers mainly revealed enrichment for cell adhesion, developmental, inflammatory, and cytoskeleton pathways. Upregulation of targeted MT1A and COMMD1 mRNA shows the liver's first response to rising intrahepatic copper concentrations. In livers with copper-associated hepatitis mainly an activation of inflammatory pathways is detected. Once the hepatitis is in the chronic stage, transcriptional differences are found in cell adhesion adaptations and cytoskeleton remodelling. In view of the high similarities in copper-associated hepatopathies between men and dog extrapolation of these dog data into human biomedicine seems feasible.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Despite repeated calls to action, proposals for urban conservation are often met with surprise or scepticism. There remains a pervasive narrative in policy, practice, and the public psyche that urban ...environments, although useful for engaging people with nature or providing ecosystem services, are of little conservation value. We argue that the tendency to overlook the conservation value of urban environments stems from misconceptions about the ability of native species to persist within cities and towns and that this, in turn, hinders effective conservation action. However, recent scientific evidence shows that these assumptions do not always hold. Although it is generally true that increasing the size, quality, and connectivity of habitat patches will improve the probability that a species can persist, the inverse is not that small, degraded, or fragmented habitats found in urban environments are worthless. In light of these findings we propose updated messages that guide and inspire researchers, practitioners, and decision makers to undertake conservation action in urban environments: consider small spaces, recognize unconventional habitats, test creative solutions, and use science to minimize the impacts of future urban development.
Corrección de Ideas Erróneas para Inspirar Acciones de Conservación en Ambientes Urbanos
Resumen
A pesar de las repetidas llamadas a actuar, las propuestas para la conservación urbana con frecuencia se enfrentan a reacciones de sorpresa o escepticismo. Todavía existe una narrativa penetrante en la política, la práctica y el psique del público que dicta que los ambientes urbanos, aunque sean útiles para comprometer a las personas con la naturaleza o para proporcionar servicios ambientales, tienen poco valor para la conservación. Argumentamos que la tendencia de pasar por alto el valor para la conservación de los ambientes urbanos surge de las ideas erróneas sobre la habilidad que tienen las especies nativas para persistir dentro de ciudades y pueblos y que esto, en cambio, impide la acción efectiva de la conservación. A pesar de esto, la evidencia científica reciente muestra que estas suposiciones no siempre se sostienen. Aunque casi siempre es verdad que incrementar el tamaño, la calidad y la conectividad de los fragmentos de hábitat mejorará la probabilidad de que una especie pueda persistir, lo contrario, que los hábitats fragmentados, degradados y pequeños que se encuentran en los ambientes urbanos son inútiles, no lo es. A la luz de estos hallazgos proponemos mensajes actualizados que guíen e inspiren a los investigadores, practicantes y a los tomadores de decisiones a emprender acciones de conservación en ambientes urbanos: considerar espacios pequeños, reconocer hábitats poco convencionales, probar con soluciones creativas, y utilizar la ciencia para minimizar los impactos de desarrollos urbanos futuros.
摘要
尽管人们一再呼吁要采取城市保护行动, 然而却常常对相关提案表示诧异或怀疑。在政策制定、实践行动和公众心理中仍存在一种普遍的认识, 即城市环境虽然有助于人们亲近自然并提供生态系统服务, 但其保护价值微乎其微。我们认为, 这种忽视城市环境保护价值的倾向来源于对本地物种在城市和乡镇间续存能力的误解, 而这反过来又阻碍了有效的保护行动。然而, 最近的科学证据表明这些种种假设并不总是成立。虽然通常情况下增加生境斑块的大小、提高其质量和连接度可以提高物种续存的可能性, 但反过来看, 并不是说退化或碎片化的小面积生境在城市环境中就毫无价值。鉴于以上发现, 我们建议更新这些指导和激励研究者、实践者和决策者采取城市环境保护行动的信息, 应考虑小尺度空间的保护、认识非传统生境、尝试创新性解决方案, 并利用科学知识来减少未来城市发展带来的影响。 【翻译: 胡怡思; 审校: 聂永刚】
Article impact statement: Conserving native biodiversity is both important and achievable in urban environments.
HLA-A*11:01 is one of the most prevalent human leukocyte antigens (HLAs), especially in East Asian and Oceanian populations. It is also highly expressed in Indigenous people who are at high risk of ...severe influenza disease. As CD8+ T cells can provide broadly cross-reactive immunity to distinct influenza strains and subtypes, including influenza A, B and C viruses, understanding CD8+ T cell immunity to influenza viruses across prominent HLA types is needed to rationally design a universal influenza vaccine and generate protective immunity especially for high-risk populations. As only a handful of HLA-A*11:01-restricted CD8+ T cell epitopes have been described for influenza A viruses (IAVs) and epitopes for influenza B viruses (IBVs) were still unknown, we embarked on an epitope discovery study to define a CD8+ T cell landscape for HLA-A*11:01-expressing Indigenous and non-Indigenous Australian people. Using mass-spectrometry, we identified IAV- and IBV-derived peptides presented by HLA-A*11:01 during infection. 79 IAV and 57 IBV peptides were subsequently screened for immunogenicity in vitro with peripheral blood mononuclear cells from HLA-A*11:01-expressing Indigenous and non-Indigenous Australian donors. CD8+ T cell immunogenicity screening revealed two immunogenic IAV epitopes (A11/PB2320-331 and A11/PB2323-331) and the first HLA-A*11:01-restricted IBV epitopes (A11/M41-49, A11/NS1186-195 and A11/NP511-520). The immunogenic IAV- and IBV-derived peptides were >90% conserved among their respective influenza viruses. Identification of novel immunogenic HLA-A*11:01-restricted CD8+ T cell epitopes has implications for understanding how CD8+ T cell immunity is generated towards IAVs and IBVs. These findings can inform the development of rationally designed, broadly cross-reactive influenza vaccines to ensure protection from severe influenza disease in HLA-A*11:01-expressing individuals.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We developed a mathematical model using a multiple source of infection framework to assess the potential effect of the expansion of highly active antiretroviral therapy (HAART) coverage among those ...in medical need on the number of individuals testing newly positive for human immunodeficiency virus (HIV) and on related costs in British Columbia, Canada, over the next 25 years. The model was calibrated using retrospective data describing antiretroviral therapy utilization and individuals testing newly positive for HIV in the province. Different scenarios were investigated on the basis of varying assumptions regarding drug resistance, adherence to HAART, therapeutic guidelines, degree of HAART coverage, and the timing of HAART uptake. Expansion of HAART lead to substantial reductions in the growth of the HIV epidemic and related costs. These results provide powerful additional motivation to accelerate the roll out ofHAARTprograms aggressively targeting those in medical need, both for their own benefit and as a means of decreasing new HIV infections.
Background
Hepatic copper accumulation causes chronic hepatitis in dogs. Mutations in the copper transporters ATP7A and ATP7B were, respectively, associated with attenuation and enhancement of ...hepatic copper concentrations in Labrador Retrievers. There is a predisposition of Dobermanns to hepatitis with increased hepatic copper concentrations.
Objectives
To investigate whether the ATP7A:c.980C>T and ATP7B:c.4358G>A mutations identified in Labrador Retrievers were associated with hepatic copper concentrations in Dobermanns.
Animals
Dobermanns from the Netherlands (n = 122) and the United States (n = 78).
Methods
In this retrospective study, mutations in ATP7A and ATP7B were investigated as risk factors for hepatic copper accumulation in Dobermanns. Liver biopsies of 200 Dobermanns were evaluated by histochemical copper staining, quantitative copper measurement, or both modalities. ATP7A and ATP7B genotypes were obtained by Kompetitive Allele Specific PCR. A linear regression model was used to investigate an association between genotype and hepatic copper concentrations.
Results
The ATP7A:c.980C>T was identified in both Dutch (2 heterozygous individuals) and American Dobermanns. In the American cohort, the minor allele frequency of the mutation was low (.081) and a possible effect on hepatic copper concentrations could not be established from this data set. A significant association of the ATP7B:c.4358G>A variant with increased hepatic copper concentrations in Dobermanns was observed.
Conclusions and Clinical Importance
The ATP7B:c.4358G>A variant could be a contributor to hepatic copper accumulation underlying the risk of development of copper‐associated hepatitis in breeds other than the Labrador Retriever.
Kidney Infarction in Patients With COVID-19 Post, Adrian; den Deurwaarder, Edwin S.G.; Bakker, Stephan J.L. ...
American journal of kidney diseases,
09/2020, Letnik:
76, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Coronavirus disease 2019 (COVID-19) is a contagious life-threatening infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent findings indicate an increased risk ...for acute kidney injury during COVID-19 infection. The pathophysiologic mechanisms leading to acute kidney injury in COVID-19 infection are unclear but may include direct cytopathic effects of the virus on kidney tubular and endothelial cells, indirect damage caused by virus-induced cytokine release, and kidney hypoperfusion due to a restrictive fluid strategy. In this report of 2 cases, we propose an additional pathophysiologic mechanism. We describe 2 cases in which patients with COVID-19 infection developed a decrease in kidney function due to kidney infarction. These patients did not have atrial fibrillation. One of these patients was treated with therapeutic doses of low-molecular-weight heparin, after which no further deterioration in kidney function was observed. Our findings implicate that the differential diagnosis of acute kidney injury in COVID-19–infected patients should include kidney infarction, which may have important preventive and therapeutic implications.
To review and update the evidence relating to the personal, social, and environmental factors associated with physical activity (PA) in adults.
Systematic review of the peer-reviewed literature to ...identify papers published between 1998 and 2000 with PA (and including exercise and exercise adherence). Qualitative reports or case studies were not included.
Thirty-eight new studies were located. Most confirmed the existence of factors already known to be correlates of PA. Changes in status were noted in relation to the influence of marital status, obesity, smoking, lack of time, past exercise behavior, and eight environmental variables. New studies were located which focused on previously understudied population groups such as minorities, middle and older aged adults, and the disabled.
The newly reported studies tend to take a broader "ecological" approach to understanding the correlates of PA and are more focused on environmental factors. There remains a need to better understand environmental influences and the factors that influence different types of PA. As most of the work in this field still relies on cross-sectional studies, longitudinal and intervention studies will be required if causal relationships are to be inferred.
Dosage of local anesthetics (LAs) used for regional anesthesia in children is not well determined. In order to evaluate and come to a consensus regarding some of these controversial topics, The ...European Society of Regional Anaesthesia and Pain Therapy (ESRA) and the American Society of Regional Anesthesia and Pain Medicine (ASRA) developed a Joint Committee Practice Advisory on Local Anesthetics and Adjuvants Dosage in Pediatric Regional Anesthesia.
Representatives from both ASRA and ESRA composed the joint committee practice advisory. Evidence-based recommendations were based on a systematic search of the literature. In cases where no literature was available, expert opinion was elicited.
Spinal anesthesia with bupivacaine can be performed with a dose of 1 mg/kg for newborn and/or infant and a dose of 0.5 mg/kg in older children (>1 year of age). Tetracaine 0.5% is recommended for spinal anesthesia (dose, 0.07-0.13 mL/kg). Ultrasound-guided upper-extremity peripheral nerve blocks (eg, axillary, infraclavicular, interscalene, supraclavicular) in children can be performed successfully and safely using a recommended LA dose of bupivacaine or ropivacaine of 0.5 to 1.5 mg/kg. Dexmedetomidine can be used as an adjunct to prolong the duration of peripheral nerve blocks in children.
High-level evidence is not yet available to guide dosage of LA used in regional blocks in children. The ASRA/ESRA recommendations intend to provide guidance in order to reduce the large variability of LA dosage currently observed in clinical practice.
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