808 research outputs found

    Teaching Open Science:Published Data and Digital Literacy in Archaeology Classrooms

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    Digital literacy has been cited as one of the primary challenges to ensuring data reuse and increasing the value placed on open science. Incorporating published data into classrooms and training is at the core of tackling this issue. This article presents case studies in teaching with different published data platforms, in three different countries (the Netherlands, Canada, and the United States), to students at different levels and with differing skill levels. In outlining their approaches, successes, and failures in teaching with open data, it is argued that collaboration with data publishers is critical to improving data reuse and education. Moreover, increased opportunities for digital skills training and scaffolding across program curriculum are necessary for managing the learning curve and teaching students the values of open science

    On the coset duals of extended higher spin theories

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    We study the holographic duality between the M x M matrix extension of Vasiliev higher spin theories on AdS3 and the large N limit of SU(N+M)/SU(N) x U(1) type cosets. We present a simplified proof for the agreement of the spectra and clarify the relation between this duality and the version in which the cosets are replaced by Kazama-Suzuki models of Grassmannian type.Comment: 27 pages, 1 tabl

    Controlling Magnetic Anisotropy in a Zero-Dimensional S=1 Magnet Using Isotropic Cation Substitution

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    The [Zn_{1–x}_Ni-{x}(HF_{2})(pyz)_{2}]SbF_{6} (x = 0.2; pyz = pyrazine) solid solution exhibits a zero-field splitting (D) that is 22% larger [D = 16.2(2) K (11.3(2) cm^{–1})] than that observed in the x = 1 material [D = 13.3(1) K (9.2(1) cm^{–1)}]. The substantial change in D is accomplished by an anisotropic lattice expansion in the MN_{4} (M = Zn or Ni) plane, wherein the increased concentration of isotropic Zn(II) ions induces a nonlinear variation in M-F and M-N bond lengths. In this, we exploit the relative donor atom hardness, where M-F and M-N form strong ionic and weak coordinate covalent bonds, respectively, the latter being more sensitive to substitution of Ni by the slightly larger Zn(II) ion. In this way, we are able to tune the single-ion anisotropy of a magnetic lattice site by Zn-substitution on nearby sites. This effect has possible applications in the field of single-ion magnets and the design of other molecule-based magnetic systems

    Mutation analysis of cell-free DNA and single circulating tumor cells in metastatic breast cancer patients with high CTC counts

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    Purpose: The purpose of this study was to directly compare mutation profiles in multiple single CTCs and cfDNA isolated from the same blood samples taken from patients with metastaic breast cancer (MBC). We aimed to determine whether cell-free DNA would reflect the heterogeneity observed in 40 single CTCs. Experimental design: CTCs were enumerated by Cellsearch. CTC count was compared with the quantity of matched cfDNA and serum CA15-3 and alkaline phosphatase (ALP) in 112 patients with metastatic breast cancer. In 5 patients with {greater than or equal to}100 CTCs, multiple individual EpCAM-positive CTCs were isolated by DEPArray and compared with matched cfDNA and primary tumour tissue by targeted next generation sequencing (NGS) of ~2200 mutations in 50 cancer genes. Results: In the whole cohort, total cfDNA levels and cell counts ({greater than or equal to}5 CTCs) were both significantly associated with overall survival, unlike CA15-3 and ALP. NGS analysis of 40 individual EpCAM-positive CTCs from 5 patients with MBC revealed mutational heterogeneity in PIK3CA, TP53, ESR1 and KRAS genes between individual CTCs. In all 5 patients cfDNA profiles provided an accurate reflection of mutations seen in individual CTCs. ESR1 and KRAS gene mutations were absent from primary tumour tissue and therefore likely reflect either a minor sub-clonal mutation or were acquired with disease progression. Conclusion: Our results demonstrate that cfDNA reflects persisting EpCAM-positive CTCs in patients with high CTC counts and therefore may enable monitoring of the metastatic burden for clinical decision-making. Experimental Design: DNA methylation was investigated in independent tumor cohorts using Illumina HumanMethylation arrays and gene expression by Affymetrix arrays and qRT-PCR. The role of Msh homeobox 1 (MSX1) in drug sensitivity was investigated by gene reintroduction and siRNA knockdown of ovarian cancer cell lines. Results: CpG sites at contiguous genomic locations within the MSX1 gene have significantly lower levels of methylation in independent cohorts of HGSOC patients, which recur by 6 months compared with after 12 months (P < 0.05, q < 0.05, n = 78), have poor RECIST response (P < 0.05, q < 0.05, n = 61), and are associated with PFS in an independent cohort (n = 146). A decrease in methylation at these CpG sites correlates with decreased MSX1 gene expression. MSX1 expression is associated with PFS (HR, 0.92; 95% CI, 0.85–0.99; P = 0.029; n = 309). Cisplatin-resistant ovarian cancer cell lines have reduced MSX1 expression, and MSX1 overexpression leads to cisplatin sensitization, increased apoptosis, and increased cisplatin-induced p21 expression. Conclusions: Hypomethylation of CpG sites within the MSX1 gene is associated with resistant HGSOC disease at presentation and identifies expression of MSX1 as conferring platinum drug sensitivity

    Shareholder rights in Britain

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    An analysis of shareholder rights in Britain and their interaction with European La

    Advances in understanding of air-sea exchange and cycling of greenhouse gases in the upper ocean

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    \ua9 2024 University of California Press. All rights reserved. The air–sea exchange and oceanic cycling of greenhouse gases (GHG), including carbon dioxide (CO2), nitrous oxide (N2O), methane (CH4), carbon monoxide (CO), and nitrogen oxides (NOx \ubc NO \ufe NO2), are fundamental in controlling the evolution of the Earth’s atmospheric chemistry and climate. Significant advances have been made over the last 10 years in understanding, instrumentation and methods, as well as deciphering the production and consumption pathways of GHG in the upper ocean (including the surface and subsurface ocean down to approximately 1000 m). The global ocean under current conditions is now well established as a major sink for CO2, a major source for N2O and a minor source for both CH4 and CO. The importance of the ocean as a sink or source of NOx is largely unknown so far. There are still considerable uncertainties about the processes and their major drivers controlling the distributions of N2O, CH4, CO, and NOx in the upper ocean. Without having a fundamental understanding of oceanic GHG production and consumption pathways, our knowledge about the effects of ongoing major oceanic changes—warming, acidification, deoxygenation, and eutrophication—on the oceanic cycling and air–sea exchange of GHG remains rudimentary at best. We suggest that only through a comprehensive, coordinated, and interdisciplinary approach that includes data collection by global observation networks as well as joint process studies can the necessary data be generated to (1) identify the relevant microbial and phytoplankton communities, (2) quantify the rates of ocean GHG production and consumption pathways, (3) comprehend their major drivers, and (4) decipher economic and cultural implications of mitigation solutions

    A novel hotspot specific isothermal amplification method for detection of the common PIK3CA p.H1047R breast cancer mutation

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    Breast cancer (BC) is a common cancer in women worldwide. Despite advances in treatment, up to 30% of women eventually relapse and die of metastatic breast cancer. Liquid biopsy analysis of circulating cell-free DNA fragments in the patients’ blood can monitor clonality and evolving mutations as a surrogate for tumour biopsy. Next generation sequencing platforms and digital droplet PCR can be used to profile circulating tumour DNA from liquid biopsies; however, they are expensive and time consuming for clinical use. Here, we report a novel strategy with proof-of-concept data that supports the usage of loop-mediated isothermal amplification (LAMP) to detect PIK3CA c.3140 A > G (H1047R), a prevalent BC missense mutation that is attributed to BC tumour growth. Allele-specific primers were designed and optimized to detect the p.H1047R variant following the USS-sbLAMP method. The assay was developed with synthetic DNA templates and validated with DNA from two breast cancer cell-lines and two patient tumour tissue samples through a qPCR instrument and finally piloted on an ISFET enabled microchip. This work sets a foundation for BC mutational profiling on a Lab-on-Chip device, to help the early detection of patient relapse and to monitor efficacy of systemic therapies for personalised cancer patient management

    The GABA transporter 1 (SLC6A1): a novel candidate gene for anxiety disorders

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    Recent evidence suggests that the GABA transporter 1 (GAT-1; SLC6A1) plays a role in the pathophysiology and treatment of anxiety disorders. In order to understand the impact of genetic variation within SLC6A1 on pathological anxiety, we performed a case–control association study with anxiety disorder patients with and without syndromal panic attacks. Using the method of sequential addition of cases, we found that polymorphisms in the 5′ flanking region of SLC6A1 are highly associated with anxiety disorders when considering the severity of syndromal panic attacks as phenotype covariate. Analysing the effect size of the association, we observed a constant increase in the odds ratio for disease susceptibility with an increase in panic severity (OR ~ 2.5 in severely affected patients). Nominally significant association effects were observed considering the entire patient sample. These data indicate a high load of genetic variance within SLC6A1 on pathological anxiety and highlight GAT-1 as a promising target for treatment of anxiety disorders with panic symptoms

    The predictive value of early behavioural assessments in pet dogs: a longitudinal study from neonates to adults

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    Studies on behavioural development in domestic dogs are of relevance for matching puppies with the right families, identifying predispositions for behavioural problems at an early stage, and predicting suitability for service dog work, police or military service. The literature is, however, inconsistent regarding the predictive value of tests performed during the socialisation period. Additionally, some practitioners use tests with neonates to complement later assessments for selecting puppies as working dogs, but these have not been validated. We here present longitudinal data on a cohort of Border collies, followed up from neonate age until adulthood. A neonate test was conducted with 99 Border collie puppies aged 2–10 days to assess activity, vocalisations when isolated and sucking force. At the age of 40–50 days, 134 puppies (including 93 tested as neonates) were tested in a puppy test at their breeders' homes. All dogs were adopted as pet dogs and 50 of them participated in a behavioural test at the age of 1.5 to 2 years with their owners. Linear mixed models found little correspondence between individuals' behaviour in the neonate, puppy and adult test. Exploratory activity was the only behaviour that was significantly correlated between the puppy and the adult test. We conclude that the predictive validity of early tests for predicting specific behavioural traits in adult pet dogs is limited
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