A tale of two worlds: A comparative study of language ecologies in Asia and the Americas

Language use patterns of individual speech communities are largely conditioned by the different language ecologies in which they are immersed. We believe this ecological stance helps explain why minority languages of Asia are more likely to be sustainable than those in the Americas. We have identified fourteen traits which characterize ecologies in general, describing how they play out differently in the Americas versus Asia. Each trait is considered to be on a continuum, with opposing values that measure whether conditions are more or less favorable to language maintenance. On one side of the continuum, we discuss the values in the Americas, and explain how these are more favorable to language shift. On the other side of the scale, we talk about the values in Asia, and explain how these are more conducive to language maintenance. To show the application of these traits, the paper also includes two in-depth case studies as prototypical examples from each area, one from the Americas and one from Asia. We conclude with some comments about how these traits can be useful for those engaged in language development work.National Foreign Language Resource Cente

Interstellar neutral helium in the heliosphere from IBEX observations. V. Observations in IBEX-Lo ESA steps 1, 2, & 3

Direct-sampling observations of interstellar neutral (ISN) He by Interstellar Boundary Explorer (IBEX) provide valuable insight into the physical state of and processes operating in the interstellar medium ahead of the heliosphere. The ISN He atom signals are observed at the four lowest ESA steps of the IBEX-Lo sensor. The observed signal is a mixture of the primary and secondary components of ISN He and H. Previously, only data from one of the ESA steps have been used. Here, we extended the analysis to data collected in the three lowest ESA steps with the strongest ISN He signal, for the observation seasons 2009-2015. The instrument sensitivity is modeled as a linear function of the atom impact speed onto the sensor's conversion surface separately for each ESA step of the instrument. We found that the sensitivity increases from lower to higher ESA steps, but within each of the ESA steps it is a decreasing function of the atom impact speed. This result may be influenced by the hydrogen contribution, which was not included in the adopted model, but seems to exist in the signal. We conclude that the currently accepted temperature of ISN He and velocity of the Sun through the interstellar medium do not need a revision, and we sketch a plan of further data analysis aiming at investigating ISN H and a better understanding of the population of ISN He originating in the outer heliosheath.Comment: 20 pages, 5 figures, 5 tables, accepted for publication in the The Astrophysical Journa

Synthesis and Anchoring of Antineoplastic Ferrocene and Phthalocyanine Derivatives on Water-Soluble Polymeric Drug Carriers Derived from Lysine and Aspartic Acid

The general synthetic strategy towards water-soluble biodegradable drug carriers and the properties that they must have are discussed. The syntheses of water-soluble biodegradable copolymers of lysine and aspartic acid as potential drug-delivering devices, having amine-functionalised side chains are then described. Covalent anchoring of carboxylic acid derivatives of the antineoplastic ferrocene and photodynamically active phthalocyanine moieties to the amine-containing drug carrier copolymers under mild coupling conditions has been achieved utilising the coupling reagent O-benzotriazolyl-N,N,N′,N′-tetramethyluronium hexafluorophosphate to promote formation of the biodegradable amide bond. Even though the parent antineoplastic ferrocene and phthalocyanine derivatives are themselves insoluble in water at pH < 7, the new carrier-drug conjugates that were obtained are well water-soluble

Human Challenge Pilot Study with Cyclospora cayetanensis

We describe a pilot study that attempted to infect human volunteers with Cyclospora cayetanensis. Seven healthy volunteers ingested an inoculum of Cyclospora oocysts (approximately 200–49,000 oocysts). The volunteers did not experience symptoms of gastroenteritis, and no oocysts were detected in any stool samples during the 16 weeks volunteers were monitored

Evaluating markers of epithelial-mesenchymal transition to identify cancer patients at risk for metastatic disease

Most cancer deaths are due to metastases. Markers of epithelial-mesenchymal transition (EMT) measured in primary tumor cancer cells could be helpful to assess patient risk of metastatic disease, even among those otherwise diagnosed with local disease. Previous studies of EMT markers and patient outcomes used inconsistent methods and did not compare the clinical impact of different expression cut points for the same marker. Using digital image analysis, we measured the EMT markers Snail and E-cadherin in primary tumor specimens from 190 subjects in tissue microarrays from a population-based prospective cohort of colorectal cancer patients and estimated their associations with time-to-death. After measuring continuous marker expression data, we performed a systematic search for the cut point for each marker with the best model fit between dichotomous marker expression and time-to-death. We also assessed the potential clinical impact of different cut points for the same marker. After dichotomizing expression status at the statistically-optimal cut point, we found that Snail expression was not associated with time-to-death. When measured as a weighted average of tumor cores, low E-cadherin expression was associated with a greater risk of dying within 5 years of surgery than high expression (risk difference = 33 %, 95 % confidence interval 3–62 %). Identifying a clinically-optimal cut point for an EMT marker requires trade-offs between strength and precision of the association with patient outcomes, as well as consideration of the number of patients whose treatments might change based on using the marker at a given cut point

Spiral Defect Chaos in Large Aspect Ratio Rayleigh-Benard Convection

We report experiments on convection patterns in a cylindrical cell with a large aspect ratio. The fluid had a Prandtl number of approximately 1. We observed a chaotic pattern consisting of many rotating spirals and other defects in the parameter range where theory predicts that steady straight rolls should be stable. The correlation length of the pattern decreased rapidly with increasing control parameter so that the size of a correlated area became much smaller than the area of the cell. This suggests that the chaotic behavior is intrinsic to large aspect ratio geometries.Comment: Preprint of experimental paper submitted to Phys. Rev. Lett. May 12 1993. Text is preceeded by many TeX macros. Figures 1 and 2 are rather lon

Rapid and robust phylotyping of spa t003, a dominant MRSA clone in Luxembourg and other European countries

Background: spa typing is a common genotyping tool for methicillin-resistant Staphylococcus aureus (MRSA) in Europe. Given the high prevalence of dominant clones, spa-typing is proving to be limited in its ability to distinguish outbreak isolates from background isolates. New molecular tools need to be employed to improve subtyping of dominant local MRSA strains (e.g., spa type t003). Methods: Phylogenetically critical, or canonical, SNPs (can-SNPs) were identified as subtyping targets through sequence analysis of 40 MRSA whole genomes from Luxembourg. Real-time PCR assays were designed around target SNPs and validated using a repository of 240 previously sub-typed and epidemiologically characterized Luxembourg MRSA isolates, including 153 community and hospital isolates, 69 isolates from long term care (LTC) facilities, and 21 prospectively analyzed MRSA isolates. Selected isolates were also analyzed by whole genome SNP typing (WGST) for comparison to the SNP assays and other subtyping techniques. Results: Fourteen real-time PCR assays were developed and validated, including two assays to determine presence of spa t003 or t008. The other twelve assays successfully provided a high degree of resolution within the t003 subtype. WGST analysis of the LTC facility isolates provided greater resolution than other subtyping tools, identifying clusters indicative of ongoing transmission within LTC facilities. Conclusions: canSNP-based PCR assays are useful for local level MRSA phylotyping, especially in the presence of one or more dominant clones. The assays designed here can be easily adapted for investigating t003 MRSA strains in other regions in Western Europe. WGST provides substantially better resolution than other typing methods

Identification of Human Papillomavirus Infection in Cancer Tissue by Targeted Next-generation Sequencing

Human papillomaviruses (HPV) are oncogenic DNA viruses implicated in squamous cell carcinomas of several anatomic sites, as well as endocervical adenocarcinomas. Identification of HPV is an actionable finding in some carcinomas, potentially influencing tumor classification, prognosis, and management. We incorporated capture probes for oncogenic HPV strains 16 and 18 into a broader next-generation sequencing (NGS) panel designed to identify actionable mutations in solid malignancies. A total of 21 head and neck, genitourinary and gynecological squamous cell carcinomas and endocervical adenocarcinomas were sequenced as part of the UNCSeq project. Using p16 immunohistochemical results as the gold standard, we set a cutoff for proportion of aligned HPV reads that maximized performance of our NGS assay (92% sensitive, 100% specific for HPV). These results suggest that sequencing of oncogenic pathogens can be incorporated into targeted NGS panels, extending the clinical utility of genomic assays

Criteria for the use of omics-based predictors in clinical trials.

The US National Cancer Institute (NCI), in collaboration with scientists representing multiple areas of expertise relevant to 'omics'-based test development, has developed a checklist of criteria that can be used to determine the readiness of omics-based tests for guiding patient care in clinical trials. The checklist criteria cover issues relating to specimens, assays, mathematical modelling, clinical trial design, and ethical, legal and regulatory aspects. Funding bodies and journals are encouraged to consider the checklist, which they may find useful for assessing study quality and evidence strength. The checklist will be used to evaluate proposals for NCI-sponsored clinical trials in which omics tests will be used to guide therapy