To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Forty years ago, Knut Fladmark (1979) argued that the Pacific Coast offered a viable alternative to the ice-free corridor model for the initial peopling of the Americas—one of the first to support a “coastal migration theory” that remained marginal for decades. Today, the pre-Clovis occupation at the Monte Verde site is widely accepted, several other pre-Clovis sites are well documented, investigations of terminal Pleistocene subaerial and submerged Pacific Coast landscapes have increased, and multiple lines of evidence are helping decode the nature of early human dispersals into the Americas. Misconceptions remain, however, about the state of knowledge, productivity, and deglaciation chronology of Pleistocene coastlines and possible technological connections around the Pacific Rim. We review current evidence for several significant clusters of early Pacific Coast archaeological sites in North and South America that include sites as old or older than Clovis. We argue that stemmed points, foliate points, and crescents (lunates) found around the Pacific Rim may corroborate genomic studies that support an early Pacific Coast dispersal route into the Americas. Still, much remains to be learned about the Pleistocene colonization of the Americas, and multiple working hypotheses are warranted.
An improved variational optimization approach is established to optimize and analyse the propulsion efficiency of the high-altitude contra-rotating propellers for high-altitude airships based on the Vortex Lattice Lifting Line Method. The optimum radial circulation distribution, chord and pitch distribution are optimized under the maximum lift-to-drag ratio of aerofoils. To consider the effects of the actual Reynolds number and the Mach number of each aerofoil section, aerodynamics such as lift coefficient, drag coefficient and lift-to-ratio are obtained by interpolating a CFD database, which is established by numerical simulations under different Reynolds number, Mach number and angles-of-attack. The improved method is verified by validation cases on a high-altitude CRP using the three-dimensional steady Reynolds-averaged Navier-Stokes solver and moving reference frames technique. The optimization results of thrust, torque and efficiency for both the individual front/rear propeller and CRP are shown to agree reasonably well with the CFD results. Using the improved approach, the influence of blade numbers, diameter, rotation speeds, axial distance and torque ratio on the optimum efficiency of CRPs is illustrated in detail by conducting parametric studies.
The Foothills Erratics Train consists of large quartzite blocks of Rocky Mountains origin deposited on the eastern slopes of the Rocky Mountain Foothills in Alberta between ~53.5°N and 49°N. The blocks were deposited in their present locations when the western margin of the Laurentide Ice Sheet (LIS) detached from the local ice masses of the Rocky Mountains, which initiated the opening of the southern end of the ice-free corridor between the Cordilleran Ice Sheet and the LIS. We use 10Be exposure dating to constrain the beginning of this decoupling. Based on a group of 12 samples well-clustered in time, we date the detachment of the western LIS margin from the Rocky Mountain front to ~14.9 ± 0.9 ka. This is ~1000 years later than previously assumed, but a lack of a latitudinal trend in the ages over a distance of ~500 km is consistent with the rapid opening of a long wedge of unglaciated terrain portrayed in existing ice-retreat reconstructions. A later separation of the western LIS margin from the mountain front implies higher ice margin–retreat rates in order to meet the Younger Dryas ice margin position near the boundary of the Canadian Shield ~2000 years later.
Rabies is one of the major public health problems in China, and the mortality rate of rabies remains the highest among all notifiable infectious diseases. A meta-analysis was conducted to investigate the post-exposure prophylaxis (PEP) vaccination rate and risk factors for human rabies in mainland China. The PubMed, Web of Science, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodical and Wanfang databases were searched for articles on rabies vaccination status (published between 2007 and 2017). In total, 10 174 human rabies cases from 136 studies were included in this meta-analysis. Approximately 97.2% (95% confidence interval (CI) 95.1–98.7%) of rabies cases occurred in rural areas and 72.6% (95% CI 70.0–75.1%) occurred in farmers. Overall, the vaccination rate in the reported human rabies cases was 15.4% (95% CI 13.7–17.4%). However, among vaccinated individuals, 85.5% (95% CI 79.8%–83.4%) did not complete the vaccination regimen. In a subgroup analysis, the PEP vaccination rate in the eastern region (18.8%, 95% CI 15.9–22.1%) was higher than that in the western region (13.3%, 95% CI 11.1–15.8%) and this rate decreased after 2007. Approximately 68.9% (95% CI 63.6–73.8%) of rabies cases experienced category-III exposures, but their PEP vaccination rate was 27.0% (95% CI 14.4–44.9%) and only 6.1% (95% CI 4.4–8.4%) received rabies immunoglobulin. Together, these results suggested that the PEP vaccination rate among human rabies cases was low in mainland China. Therefore, standardised treatment and vaccination programs of dog bites need to be further strengthened, particularly in rural areas.
A nonlinear station-keeping control method for a multi-vectored propeller airship under unknown wind field with thrust saturation is developed, which is composed of three modules: nonlinear model predictive controller (NMPC), disturbance observer (DOB) and tracking differentiator (TD). The nonlinear kinematics and dynamics models are introduced, and the wind effect is considered by the wind-induced aerodynamic force. Based on both models, an explicit NMPC is designed. Then a nonlinear DOB is introduced to estimate the wind disturbance. A TD, showing the relationship between the maximum propulsion force and the maximum flight acceleration, is proposed to handle the thrusts’ amplitude saturation. Stability analysis shows that the closed-loop system is globally asymptotically stable. Simulations for a multi-vectored propeller airship are conducted to demonstrate the robustness and effectiveness of the proposed method.
OBJECTIVES/SPECIFIC AIMS: Despite aggressive chemotherapy, surgical resection, and radiation therapy, glioblastoma remains almost universally fatal. In a pilot, randomized, and blinded clinical trial, we recently demonstrated that administration of RNA-loaded DC vaccines was associated with significantly improved progression-free and overall survival in patients with glioblastoma (Mitchell et al., Nature, 2015). Furthermore, clinical outcomes correlated with DC migration to vaccine-site draining lymph nodes measured by Indium-111 labeling of RNA-loaded DCs and SPECT/CT imaging. Although these studies demonstrated that tracking DC migration may be an important clinical biomarker for response to DC vaccination, the complexity and regulatory requirements associated with nuclear labelling to track DC migration limits widespread application of this technique. We have therefore developed RNA-loaded magnetic nanoparticles (RNA-NPs) to enhance DC migration to LNs and track that migration with a widely available imaging modality (i.e., MRI). METHODS/STUDY POPULATION: Cationic liposomes were loaded with iron oxide nanoparticles with or without cholesterol. The resulting nanoparticles were complexed with RNA and used to transfect DCs ex vivo. RNA-NP-loaded DsRed+ DCs were then injected intradermally into mice and tracked noninvasively with T2-weighted 11T MRI before excision and quantification with flow cytometry. RESULTS/ANTICIPATED RESULTS: In vitro experiments demonstrate that iron oxide loading does not reduce RNA-NP-mediated transfection of DCs. Additionally, replacement of cationic lipids with cholesterol increased RNA-NP transfection of the DC2.4 cell line and enhanced the T cell stimulatory capacity of treated bone marrow-derived dendritic cells (BMDCs). Compared to electroporation, RNA-NPs enhanced DC migration to lymph nodes and reduced T2 MRI intensity in DC-bearing lymph nodes. DISCUSSION/SIGNIFICANCE OF IMPACT: This data suggests that iron oxide-loaded RNA-NPs enable noninvasive cell tracking with MRI and enhance DC migration to lymph nodes. We have further shown that inclusion of cholesterol in RNA-NPs augments the stimulatory capacity of transfected DCs. Future work will consider effects of RNA-NPs on antitumor immune responses and the utility of MRI-detected DC migration as a biomarker of vaccine efficacy.
Two new species of egg parasitoids, Oobius saimaensis Yao and Mottern new species and Oobius fleischeri Yao and Duan new species (Hymenoptera: Encyrtidae), are described from eggs of Agrilus fleischeri Obenberger, 1925 (Coleoptera: Buprestidae). Agrilus fleischeri is a phloem-feeding woodborer of poplar (Populus Linnaeus; Salicaceae) in northeastern China. These two species can be distinguished morphologically as O. fleischeri has five tarsomeres and O. saimaensis has four tarsomeres. Although O. saimaensis is morphologically similar to its sympatric congener O. agrili Zhang and Hang, 2005, an important natural enemy of the invasive emerald ash borer, Agrilus planipennis Fairmaire, 1888, molecular phylogenetics and morphological data indicate that they are distinct species. Phylogenetic relationships among the new species and other closely related species are also inferred by using DNA sequence data from several ribosomal and mitochondrial genes. In addition, we expand the known distribution of Oobius primorskyensis Yao and Duan, 2016 to include South Korea.
We report daptomycin minimum inhibitory concentrations (MICs) for vancomycin-resistant Enterococcus faecium isolated from bloodstream infections over a 4-year period. The daptomycin MIC increased over time hospital-wide for initial isolates and increased over time within patients, culminating in 40% of patients having daptomycin-nonsusceptible isolates in the final year of the study.
Nutraceuticals have generated interest as a way to mitigate the cognitive decline in older adults. The aim of this systematic review was to determine the evidence for these claims from the scientific literature in randomised, double-blinded, controlled trials (duration: ≥1 year; participants: n≥100; age(mean): ≥65 years). Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched four electronic databases (PubMed, Scopus, CINAHL and Web of Science) and identified twenty-five studies published between the 15·June·2006 and 14·June·2016. Interventions included B-vitamins, n-3 fatty acids, antioxidant vitamins and herbs. Of the B-vitamin studies, four found benefits to cognition with supplementation. The first of these B-vitamin studies, in individuals with mild cognitive impairment (n 266; duration=2 years), included benefit to executive function (P=0·015) and improvements in the Mini-Mental State Examination (MMSE) among participants with baseline homocysteine above 11·3 µmol/l (P<0·001). In the same sample, the second study found cognitive benefits of B-vitamins dependent on the higher baseline plasma n-3 fatty acid status. The third B-vitamin study (n 900; duration=2 years) reported improved performance in immediate (P=0·046) and delayed recall (P=0·013), whereas the fourth study (n 856; duration=2 years) reported slower rate of cognitive decline in the MMSE (P=0·05). One study investigating DHA treatment (n 402; duration=1·5 years) revealed the slower rate of cognitive change in apoE e4 non-carriers (P=0·03). As only five included studies revealed notable benefits, presently based on the specific compounds explored here, there is not compelling evidence to support the use nutraceuticals to improve cognition in the elderly. Future long-term trials of nutraceuticals should investigate interactions with lifestyle, blood biomarkers and genetic risk factors.
Holocene tephrostratigraphy in Alaska provides independent chronology and stratigraphic correlation in a region where reworked old (Holocene) organic carbon can significantly distort radiocarbon chronologies. Here, we present new glass chemistry and chronology for Holocene tephras preserved in three Alaskan lakes: one in the eastern interior and two in the southern Brooks Range. Tephra beds in the eastern interior lake-sediment core are correlated with the White River Ash and the Hayes tephra set H (~4200–3700 cal yr BP), and an additional discrete tephra bed is likely from the Aleutian arc/Alaska Peninsula. Cryptotephras (nonvisible tephras) found in the Brooks Range include the informally named “Ruppert tephra” (~2700–2300 cal yr BP) and the Aniakchak caldera-forming event II (CFE II) tephra (~3600 cal yr BP). A third underlying Brooks Range cryptotephra is chemically indistinguishable from the Aniakchak CFE II tephra (4070–3760 cal yr BP) and is likely to be from an earlier eruption of the Aniakchak volcano.
In the theory research and engineering practice, more basic inflatable models are essential for the mechanical property analysis of inflatable structures. Firstly, this paper presents a model of the tapered inflatable cantilever beam based on Timoshenko's theory and analyzes its deformation under a concentrated force. Moreover, the following forces resulting from internal pressure and taper ratio are introduced into the equilibrium equations of the deformed configuration. Thus, the model is optimized compared to the existing one for a straight beam. To verify the effectiveness and the superiority of the established model, the theoretical method based on the model and FEM method are compared by adopting an example about the tapered beams. Finally, the theoretical method is applied in analyzing the influence of geometry and estimating a valid range of taper ratio. By the criterion of the same amount material area, the optimum taper ratio is obtained.
APETALA2/ethylene-responsive factor (AP2/ERF) family transcription factors play a vital role in plant growth and in response to hormones and abiotic stresses. In the current research, it is reported that OsDERF2, one of the drought-responsive ERF, is a member of the DREB sub-family. OsDERF2 is a nuclear-localized protein and has transcriptional activity in yeast. Expression of OsDERF2 was induced by drought and inhibited by abscisic acid (ABA). However, OsDERF2 RNA interference (RNAi) knock-down transgenic lines enhanced tolerance to drought stress at seedling stage and were much more sensitive to ABA treatment, which may result from the increased ABA level in vivo. The basic leucine zipper (bZIP) transcription factor family plays an important role in the ABA signalling pathway of abiotic stress. Quantitative real-time polymerase chain reaction analysis revealed that the bZIP family gene OsbZIP20 and ABA-response gene OsABA45 were up-regulated 25 times and 120 times, respectively, in OsDERF2 RNAi knock-down lines under drought stress, which were up-regulated five and seven times in wild type under drought stress. The current data reveal that OsDERF2 negatively modulates drought stress response in an ABA-mediated pathway through regulating gene expression of other ABA-response transcription factors.
A scheme for the improvement of proton beam quality by the optimized dragging field from the interaction of ultraintense laser pulse with a complex double-layer target is proposed and demonstrated by one-dimensional particle-in-cell (Opic1D) simulations. The complex double-layer target consists of an overdense proton thin foil followed by a mixed hydrocarbon (CH) underdense plasma. Because of the existence of carbon ions, the dragging field in the mixed CH underdense plasma becomes stronger and flatter in the location of the proton beam than that in a pure hydrogen (H) underdense plasma. The optimized dragging field can keep trapping and accelerating protons in the mixed CH underdense target to high quality. Consequently, the energy spread of the proton beam in the mixed CH underdense plasma can be greatly reduced down to 2.6% and average energy of protons can reach to 9 GeV with circularly polarized lasers at intensities 2.74 × 1022 W/cm2.