Abstract
Resistance to targeted cancer drugs is thought to result from selective pressure exerted by a high drug dose. Partial inhibition of multiple components in the same oncogenic signalling ...pathway may add up to complete pathway inhibition, while decreasing the selective pressure on each component to acquire a resistance mutation. We report here testing of this Multiple Low Dose (MLD) therapy model in
EGFR
mutant NSCLC. We show that as little as 20% of the individual effective drug doses is sufficient to completely block MAPK signalling and proliferation when used in 3D (RAF + MEK + ERK) or 4D (EGFR + RAF + MEK + ERK) inhibitor combinations. Importantly,
EGFR
mutant NSCLC cells treated with MLD therapy do not develop resistance. Using several animal models, we find durable responses to MLD therapy without associated toxicity. Our data support the notion that MLD therapy could deliver clinical benefit, even for those having acquired resistance to third generation EGFR inhibitor therapy.
Superconductivity and charge density waves (CDWs) are competitive, yet coexisting, orders in cuprate superconductors. To understand their microscopic interdependence, a probe capable of discerning ...their interaction on its natural length and time scale is necessary. We use ultrafast resonant soft x-ray scattering to track the transient evolution of CDW correlations in YBa
Cu
O
after the quench of superconductivity by an infrared laser pulse. We observe a nonthermal response of the CDW order characterized by a near doubling of the correlation length within ≈1 picosecond of the superconducting quench. Our results are consistent with a model in which the interaction between superconductivity and CDWs manifests inhomogeneously through disruption of spatial coherence, with superconductivity playing the dominant role in stabilizing CDW topological defects, such as discommensurations.
When an epidemic started in the Chinese city of Wuhan in December 2019, coronavirus was identified as the cause. Infection by the virus occurs through the interaction of viral S protein with the ...hosts' angiotensin-converting enzyme 2. By leveraging resources such as the DrugBank database and bioinformatics techniques, ligands with potential activity against the SARS-CoV-2 spike protein were designed and identified in this investigation. The FTMap server and the Molegro software were used to determine the active site of the Spike-ACE2 protein's crystal structure. Virtual screening was performed using a pharmacophore model obtained from antiparasitic drugs, obtaining 2000 molecules from molport
. The ADME/Tox profiles were used to identify the most promising compounds with desirable drug characteristics. The binding affinity investigation was then conducted with selected candidates. A molecular docking study showed five structures with better binding affinity than hydroxychloroquine. Ligand_003 showed a binding affinity of -8.645 kcal·mol
, which was considered an optimal value for the study. The values presented by ligand_033, ligand_013, ligand_044, and ligand_080 meet the profile of novel drugs. To choose compounds with favorable potential for synthesis, synthetic accessibility studies and similarity analyses were carried out. Molecular dynamics and theoretical IC
values (ranging from 0.459 to 2.371 µM) demonstrate that these candidates are promising for further tests. Chemical descriptors showed that the candidates had strong molecule stability. Theoretical analyses here show that these molecules have potential as SARS-CoV-2 antivirals and therefore warrant further investigation.
The trade in wild meat is an important economic component of rural people's livelihoods, but it has been perceived to be among the main causes of the decline of wildlife species. Recently, the ...COVID‐19 pandemic has brought to light an additional concern of wildlife markets as a major human‐health challenge. We analyzed data from the largest longitudinal monitoring (1973–2018) of the most important urban wild‐meat markets in Iquitos, Peru, to examine the trends in and impacts of these markets on people's livelihoods. Over the last 45 years, wild meat sales increased at a rate of 6.4 t/year (SD 2.17), paralleling urban population growth. Wild meat sales were highest in 2018 (442 t), contributing US$2.6 million (0.76%) to the regional gross domestic product. Five species of ungulates and rodents accounted for 88.5% of the amount of biomass traded. Vulnerable and Endangered species represented 7.0% and 0.4% of individuals sold, respectively. Despite growth in sales, the contribution of wild meat to overall urban diet was constant: 1–2%/year of total meat consumed. This result was due to greater availability and higher consumption of cheaper meats (e.g., in 2018, poultry was 45.8% cheaper and was the most consumed meat) coupled with the lack of economic incentives to harvest wild meat species in rural areas. Most wild meat was sold salted or smoked, reducing the likelihood of foodborne diseases. Community‐based wildlife management plans and the continued trade bans on primates and threatened taxa may avoid biodiversity loss. Considering the recent COVID‐19 pandemic, future management plans should include potential viral hosts and regulation and enforcement of hygiene practices in wild‐meat markets.
Comercio de Carne de Monte en los Últimos 45 Años en la Amazonia Peruana
Resumen
El comercio de carne de monte es un componente económico importante del sustento de habitantes de zonas rurales, pero se ha percibido como una de las principales causas de la declinación de especies de vida silvestre. Recientemente, la pandemia de COVID‐19 ha traído a la luz una preocupación adicional de los mercados de vida silvestre como un reto importante para la salud humana. Analizamos datos del monitoreo longitudinal más extenso (1973‐2018) de los mercados urbanos de carne de monte más importantes en Iquitos, Perú, para examinar las tendencias y los impactos de estos mercados sobre el sustento de los habitantes. Las ventas de carne de monte incrementaron en los últimos 45 años a una tasa de 6.4 t/año (DS 2.17), en paralelo con el crecimiento de la población. Las ventas de carne de monte fueron más altas en 2018 (442 t), aportando U.S. $2.6 millones (0.76%) al producto interno bruto de la región. Cinco especies de ungulados y roedores comprendieron el 88.5% de la biomasa comercializada. Especies vulnerables y en peligro representaron 7.0% y 0.4% de los individuos vendidos, respectivamente. A pesar del incremento de las ventas, la contribución de la carne de monte al total de la dieta urbana fue constante: 1–2%/año del total de carne consumida. Este resultado se debió a una mayor disponibilidad y consumo de carnes más baratas (e. g., en 2018 la carne de pollo fue 45.8% más barata y fue la más consumida) aparejado con la falta de incentivos económicos para cosechar carne de especies silvestres en áreas rurales. La mayor parte de la carne de monte se vendía salada o ahumada, reduciendo con ello la probabilidad de enfermedades transmitidas por alimentos. Los planes de manejo de vida silvestre basados en comunidades y la prohibición continua del comercio de primates y taxa amenazados pueden evitar la pérdida de biodiversidad. Considerando la reciente pandemia de COVID‐19, los planes de manejo futuros deben incluir potenciales huéspedes virales y la regulación y aplicación de prácticas de higiene en los mercados de carne de especies silvestres.
抽象
摘要: 野味贸易是农村人民维持生计的重要经济组成部分, 但也一直被认为是野生动物数量下降的主要原因之一。近期的新冠肺炎疫情暴露了野生动物市场另一个令人担忧的问题, 即对人类健康的重大挑战。本研究利用秘鲁伊基托斯市区内最重要的野味市场的最大纵向监测数据集 (1973–2018 年), 分析了野味市场的趋势及其对人们生计的影响。在过去的 45 年里, 野味销售量以每年 6.4 吨 (标准差 2.17) 的速度增长, 与城市人口增长同步。 2018 年野味的销售量最高 (442 吨), 为该地区国内生产总值贡献了 260 万美元 (0.76%) 。其中五种有蹄类和啮齿类动物占交易重量的 88.5%。易危物种和濒危物种分别占售出个体的7.0%和0.4%。尽管野味销售量有所增长, 但它对城市整体饮食的贡献仍保持不变, 占每年肉类消费总量的 1%–2%。这一结果是由于廉价的肉类有更高的供应量和消费量 (例如, 2018 年家禽价格比野味便宜 45.8%, 是消费最多的肉类), 再加上农村地区捕猎野味物种缺乏经济激励。此外, 该地区大多数野味都是腌制或熏制后出售的, 降低了导致食源性疾病的可能性。基于社区的野生动物管理计划以及对灵长类动物和受威胁物种的长期贸易禁令可能有助于遏制生物多样性丧失。考虑到近期的新冠肺炎疫情, 未来的管理计划应将潜在病毒宿主及野味市场卫生规范监管与执行纳入考虑。【翻译: 胡怡思; 审校: 聂永刚】
Article impact statement: Community‐based wildlife management, trade bans for threatened taxa and enforced hygiene practices in wild meat markets are needed to protect biodiversity and public health.
Borges RP, Sousa‐Neto MD, Versiani MA, Rached‐Júnior FA, De‐Deus G, Miranda CES, Pécora JD. Changes in the surface of four calcium silicate‐containing endodontic materials and an epoxy resin‐based ...sealer after a solubility test. International Endodontic Journal, 45, 419–428, 2012.
Aim To compare the changes in the surface structure and elemental distribution, as well as the percentage of ion release, of four calcium silicate‐containing endodontic materials with a well‐established epoxy resin‐based sealer, submitted to a solubility test.
Methodology Solubility of AH Plus, iRoot SP, MTA Fillapex, Sealapex and MTA‐Angelus (MTA‐A) was tested according to ANSI/ADA Specification 57. The deionized water used in the solubility test was submitted to atomic absorption spectrophotometry to determine and quantify Ca2+, Na+, K+, Zn2+, Ni2+ and Pb2+ ions release. In addition, the outer and inner surfaces of nonsubmitted and submitted samples of each material to the solubility test were analysed by means of scanning electron microscopy and energy‐dispersive spectroscopy (SEM/EDX). Statistical analysis was performed by using one‐way anova and Tukey’s post hoc tests (α = 0.05).
Results Solubility results, in percentage, sorted in an increasing order were −1.24 ± 0.19 (MTA‐A), 0.28 ± 0.08 (AH Plus), 5.65 ± 0.80 (Sealapex), 14.89 ± 0.73 (MTA Fillapex) and 20.64 ± 1.42 (iRoot SP). AH Plus and MTA‐A were statistically similar (P > 0.05), but different from the other materials (P < 0.05). High levels of Ca2+ ion release were observed in all groups except AH Plus sealer. MTA‐A also had the highest release of Na2+ and K+ ions. Zn+2 ion release was observed only with AH Plus and Sealapex sealers. After the solubility test, all surfaces had morphological changes. The loss of matrix was evident and the filler particles were more distinguishable. EDX analysis displayed high levels of calcium and carbon at the surface of Sealapex, MTA Fillapex and iRoot SP.
Conclusions AH Plus and MTA‐A were in accordance with ANSI/ADA’s requirements regarding solubility whilst iRoot SP, MTA Fillapex and Sealapex did not fulfil ANSI/ADA’s protocols. High levels of Ca2+ ion release were observed in all materials except AH Plus. SEM/EDX analysis revealed that all samples had morphological changes in both outer and inner surfaces after the solubility test. High levels of calcium and carbon were also observed at the surface of all materials except AH Plus and MTA‐A.
The switch from hunting wild meat for home consumption to supplying more lucrative city markets in Amazonia can adversely affect some game species. Despite this, information on the amounts of wild ...meat eaten in Amazonian cities is still limited. We estimated wild meat consumption rates in 5 cities in the State of Amazonas in Brazil through 1046 door‐to‐door household interviews conducted from 2004 to 2012. With these data, we modeled the relationship between wild meat use and a selection of socioeconomic indices. We then scaled up our model to determine the amounts of wild meat likely to be consumed annually in the 62 urban centers in central Amazonia. A total of 80.3% of all interviewees reported consuming wild meat during an average of 29.3 (CI 11.6) days per year. Most wild meat was reported as bought in local markets (80.1%) or hunted by a family member (14.9%). Twenty‐one taxa were cited as consumed, mostly mammals (71.6%), followed by reptiles (23.2%) and then birds (5.2%). The declared frequency of wild meat consumption was positively correlated with the proportion of rural population as well as with the per capita gross domestic product of the municipality (administrative divisions) where the cities were seated. We estimated that as much as 10,691 t of wild meat might be consumed annually in the 62 urban centers within central Amazonia, the equivalent of 6.49 kg per person per year. In monetary terms, this amounts to US$21.72 per person per year or US$35.1 million overall, the latter figure is comparable to fish and timber production in the region. Given this magnitude of wild meat trade in central Amazonia, it is fundamental to integrate this activity into the formal economy and actively develop policies that allow the trade of more resilient taxa and restrict trade in species sensitive to hunting.
Mercado y Consumo Urbano de Carne Silvestre en la Amazonia Central
Resumen
El cambio de la caza de animales silvestres para consumo del hogar a caza para surtir mercados urbanos más lucrativos en la Amazonia puede afectar negativamente a algunas especies de caza. A pesar de esto, la información sobre la cantidad de carne silvestre que se consume en las ciudades de la Amazonia todavía es limitada. Estimamos las tasas de consumo de carne silvestre en cinco ciudades del Estado de Amazonas, Brasil, por medio de 1046 entrevistas presenciales a hogares realizadas entre 2004 y 2012. Con estos datos modelamos la relación entre el uso de la carne silvestre y una selección de índices socioeconómicos. Después aumentamos nuestro modelo para determinar la cantidad de carne silvestre que tal vez se consume anualmente en los 62 centros urbanos de la Amazonia central. Un total de 80.3% de todos los entrevistados reportaron el consumo de carne silvestre durante un promedio de 29.3 (CI 11.6) días por año. La mayoría de la carne silvestre fue reportada como comprada en mercados locales (80.1%) o cazada por algún integrante de la familia (14.9%). Se citaron 21 taxones como parte del consumo, principalmente mamíferos (71.6%), seguidos por reptiles (23.2%) y aves (5.2%). La frecuencia declarada de consumo de carne silvestre estuvo correlacionada positivamente con la proporción de población rural, así como con el producto doméstico bruto per cápita de la municipalidad (divisiones administrativas) en donde se encuentran las ciudades. Estimamos que un máximo de 10,691 toneladas de carne silvestre podrían ser consumidas anualmente en los 62 centros urbanos de la Amazonia central, el equivalente a 6.49 kg/persona/año. En términos monetarios, esto equivale a US$21.72/persona/año o US$35.1 millones en general. Esta última cifra es comparable con la producción de madera y de peces en la región. Dada esta magnitud del mercado de carne silvestre en la Amazonia central, es fundamental la integración de esta actividad en la economía formal y el desarrollo activo de políticas que permitan el mercado de taxones más resilientes y que restrinjan el mercado para las especies sensibles a la caza.
摘要
在亚马逊地区, 对野生动物的狩猎从供家庭食用到供应利润更高的城市市场的转变, 可能对一些狩猎物种产生负面影响。尽管如此, 关于亚马逊城市食用野生动物肉类的数量信息仍然很少。我们通过 2004‐2012 年间的 1046 次上门访问, 估计了巴西亚马逊州五个城市的野生动物肉类食用量, 并利用这些数据分析了野生动物肉类利用与一些社会经济指数的关系。接下来, 我们利用这个模型模拟了亚马逊中部六十二个城市中心区每年的野生动物肉类食用量。结果显示, 总计 80.3% 的受访者报告每年平均 29.3 天 (CI为 11.6 天) 食用野生动物肉; 大部分肉类购自当地市场 (80.1%) 或由家庭成员狩猎获得 (14.9%) ; 食用的肉类来自二十一个类群, 主要是哺乳动物 (71.6%) 、爬行动物 (23.2%) 和鸟类 (5.2%) ; 野生动物肉类的食用频率与农村人口比例及其城市所在行政区的人均国内生产总值呈正相关。我们估计亚马逊中部地区六十二个城市中心区每年野生动物肉的食用量高达 10691 吨, 相当于每人每年食用 6.49 千克。按货币计算, 即每人每年食用 21.58 美元的野生动物肉, 或每年总计食用 3510 万美元的肉类, 后者相当于该地区采矿及木材生产总额。鉴于亚马逊中部地区野生动物肉类交易的规模之大, 应将这一活动纳入正式经济活动, 积极制定政策来支持开展那些较强恢复能力物种的交易, 而限制交易对狩猎敏感的物种。【翻译: 胡怡思; 审校: 聂永刚】
Article impact statement: In central Amazonia, wild meat is widely consumed by urban residents; its trade generates as much as the fish and timber industries.
The current manuscript describes the use of a heteropolyacid-containing task-specific ionic liquid, supported in imidazolium-based ionic liquids, as the catalyst for an efficient multicomponent ...synthesis of hexahydroimidazo1,2-αpyridine derivatives. The reactions conditions were fully optimized, and the bridgehead nitrogen heterocycle derivatives could be obtained in just 1 h exclusively as a single isomer (trans). Single crystal X-ray analysis confirmed the trans derivative as the only isomer. The mechanism of the reaction was investigated by ESI(+)-MS(/MS), and the use of the elegant charge-tag strategy allowed a catalytic cycle to be proposed for the current transformation and revealed the possibility of at least two reaction pathways. One derivative bearing a coumarin scaffold was synthesized, and its fluorescent properties allowed it to be tested as a probe for live-cell imaging experiments with a preference for mitochondria.
In this paper the kinetics and dynamics of nickel adsorption on calcined Bofe bentonite clay were studied. The clay was characterized through EDX, surface area (BET) and XRD analysis. The influence ...of parameters (pH, amount of adsorbent, adsorbate concentration and temperature) was investigated. Kinetic models were evaluated in order to identify potential adsorption process mechanisms. The Langmuir and Freundlich models were utilized for the analysis of adsorption equilibrium. Thermodynamic parameters were assessed as a function of the process temperature. The kinetics data were better represented by the second-order model. The process was found to be strongly influenced by the factors studied. The Bofe clay removed nickel with maximum adsorption capacity of 1.91
mg metal/g of clay (20
°C; pH 5.3) and that the thermodynamic data indicated that the adsorption reaction is spontaneous and of an exothermal nature. The Langmuir model provided the best fit for sorption isotherms.
The Aedes aegypti mosquito is the main hematophagous vector responsible for arbovirus transmission in Brazil. The disruption of A. aegypti hematophagy remains one of the most efficient and least ...toxic methods against these diseases and, therefore, efforts in the research of new chemical entities with repellent activity have advanced due to the elucidation of the functionality of the olfactory receptors and the behavior of mosquitoes. With the growing interest of the pharmaceutical and cosmetic industries in the development of chemical entities with repellent activity, computational studies (e.g., virtual screening and molecular modeling) are a way to prioritize potential modulators with stereoelectronic characteristics (e.g., pharmacophore models) and binding affinity to the AaegOBP1 binding site (e.g., molecular docking) at a lower computational cost. Thus, pharmacophore- and docking-based virtual screening was employed to prioritize compounds from Sigma-Aldrich® (n = 126,851) and biogenic databases (n = 8766). In addition, molecular dynamics (MD) was performed to prioritize the most potential potent compounds compared to DEET according to free binding energy calculations. Two compounds showed adequate stereoelectronic requirements (QFIT > 81.53), AaegOBP1 binding site score (Score > 42.0), volatility and non-toxic properties and better binding free energy value (∆G < −24.13 kcal/mol) compared to DEET ((N,N-diethyl-meta-toluamide)) (∆G = −24.13 kcal/mol).
Sensing in the collaborative Internet of Things Borges Neto, João B; Silva, Thiago H; Assunção, Renato Martins ...
Sensors (Basel, Switzerland),
03/2015, Letnik:
15, Številka:
3
Journal Article
Recenzirano
Odprti dostop
We are entering a new era of computing technology, the era of Internet of Things (IoT). An important element for this popularization is the large use of off-the-shelf sensors. Most of those sensors ...will be deployed by different owners, generally common users, creating what we call the Collaborative IoT. This collaborative IoT helps to increase considerably the amount and availability of collected data for different purposes, creating new interesting opportunities, but also several challenges. For example, it is very challenging to search for and select a desired sensor or a group of sensors when there is no description about the provided sensed data or when it is imprecise. Given that, in this work we characterize the properties of the sensed data in the Internet of Things, mainly the sensed data contributed by several sources, including sensors from common users. We conclude that, in order to safely use data available in the IoT, we need a filtering process to increase the data reliability. In this direction, we propose a new simple and powerful approach that helps to select reliable sensors. We tested our method for different types of sensed data, and the results reveal the effectiveness in the correct selection of sensor data.
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