500 research outputs found

    Laos - language situation

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    Laos features a high level of linguistic diversity, with more than 70 languages from four different major language families (Tai, Mon-Khmer, Hmong-Mien, Tibeto-Burman). Mon-Khmer languages were spoken in Laos earlier than other languages, with incoming migrations by Tai speakers (c. 2000 years ago) and Hmong-Mien speakers (c. 200 years ago). There is widespread language contact and multilingualism in upland minority communities, while lowland-dwelling Lao speakers are largely monolingual. Lao is the official national language. Most minority languages are endangered, with a few exceptions (notably Hmong and Kmhmu). There has been relatively little linguistic research on languages of Laos, due to problems of both infrastructure and administration

    Improving County-Based Science Programs: Bringing Out the Science Teacher in Your Volunteer Leaders

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    4-H programs can play an important role in increasing children\u27s exposure to, and interest in, science. To be effective, however, specialized training for volunteer leaders is needed. A method of training adult volunteer leaders to train 4-H teens to be cross-age teachers of an inquiry-based science program was designed and evaluated. Key components of this method were specific scaffolding strategies, including modeling, coaching, effective questioning, promoting group interactions, and encouraging independent investigation and thinking. Data from focus group interviews and quantitative measures showed improvement at all levels of project involvement: Adult volunteer leaders, 4-H teens, and participating 4-H youth

    Monitoring the response to neoadjuvant hormone therapy for locally advanced breast cancer using three-dimensional time-resolved optical mammography.

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    Optical mammography is a functional imaging technique that uses near-infrared light to produce three-dimensional breast images of tissue oxygen saturation and hemoglobin concentration. It has been used to monitor the response to neoadjuvant chemotherapy in breast cancer patients. We present the first results on monitoring tumor response to hormone therapy using optical mammography. We present three case studies from postmenopausal women treated with neoadjuvant hormone therapy for locally advanced breast cancer. The women were scanned before starting treatment, once during treatment, and then before surgery. Changes in physiological and optical properties within the tumor and in the rest of the breast were evaluated. At the time of surgery, two patients partially responded to treatment and one did not respond. The patients that partially responded on ultrasound revealed a corresponding recovery to normal in the hemoglobin concentration images, whereas the nonresponder indicated an increase in hemoglobin concentration in the tumor compared to her pretreatment images. These case studies suggest that optical imaging of the breast during neoadjuvant hormone treatment can provide potentially valuable information, and that physiological changes within the tumor can be seen in response to treatment

    DNA Extraction from Paraffin Embedded Material for Genetic and Epigenetic Analyses

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    Disease development and progression are characterized by frequent genetic and epigenetic aberrations including chromosomal rearrangements, copy number gains and losses and DNA methylation. Advances in high-throughput, genome-wide profiling technologies, such as microarrays, have significantly improved our ability to identify and detect these specific alterations. However as technology continues to improve, a limiting factor remains sample quality and availability. Furthermore, follow-up clinical information and disease outcome are often collected years after the initial specimen collection. Specimens, typically formalin-fixed and paraffin embedded (FFPE), are stored in hospital archives for years to decades. DNA can be efficiently and effectively recovered from paraffin-embedded specimens if the appropriate method of extraction is applied. High quality DNA extracted from properly preserved and stored specimens can support quantitative assays for comparisons of normal and diseased tissues and generation of genetic and epigenetic signatures 1. To extract DNA from paraffin-embedded samples, tissue cores or microdissected tissue are subjected to xylene treatment, which dissolves the paraffin from the tissue, and then rehydrated using a series of ethanol washes. Proteins and harmful enzymes such as nucleases are subsequently digested by proteinase K. The addition of lysis buffer, which contains denaturing agents such as sodium dodecyl sulfate (SDS), facilitates digestion 2. Nucleic acids are purified from the tissue lysate using buffer-saturated phenol and high speed centrifugation which generates a biphasic solution. DNA and RNA remain in the upper aqueous phase, while proteins, lipids and polysaccharides are sequestered in the inter- and organic-phases respectively. Retention of the aqueous phase and repeated phenol extractions generates a clean sample. Following phenol extractions, RNase A is added to eliminate contaminating RNA. Additional phenol extractions following incubation with RNase A are used to remove any remaining enzyme. The addition of sodium acetate and isopropanol precipitates DNA, and high speed centrifugation is used to pellet the DNA and facilitate isopropanol removal. Excess salts carried over from precipitation can interfere with subsequent enzymatic assays, but can be removed from the DNA by washing with 70% ethanol, followed by centrifugation to re-pellet the DNA 3. DNA is re-suspended in distilled water or the buffer of choice, quantified and stored at -20°C. Purified DNA can subsequently be used in downstream applications which include, but are not limited to, PCR, array comparative genomic hybridization 4 (array CGH), methylated DNA Immunoprecipitation (MeDIP) and sequencing, allowing for an integrative analysis of tissue/tumor samples

    Multiple Components of the VHL Tumor Suppressor Complex Are Frequently Affected by DNA Copy Number Loss in Pheochromocytoma

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    Pheochromocytomas (PCC) are rare tumors that arise in chromaffin tissue of the adrenal gland. PCC are frequently inherited through predisposing mutations in genes such as the von Hippel-Lindau (VHL) tumor suppressor. VHL is part of the VHL elongin BC protein complex that also includes CUL2/5, TCEB1, TCEB2, and RBX1; in normoxic conditions this complex targets hypoxia-inducible factor 1 alpha (HIF1A) for degradation, thus preventing a hypoxic response. VHL inactivation by genetic mechanisms, such as mutation and loss of heterozygosity, inhibits HIF1A degradation, even in the presence of oxygen, and induces a pseudohypoxic response. However, the described <10% VHL mutation rate cannot account for the high frequency of hypoxic response observed. Indeed, little is known about genetic mechanisms disrupting other complex component genes. Here, we show that, in a panel of 171 PCC tumors, 59.6% harbored gene copy number loss (CNL) of at least one complex component. CNL significantly reduced gene expression and was associated with enrichment of gene targets controlled by HIF1. Interestingly, we show that VHL-related renal clear cell carcinoma harbored disruption of VHL alone. Our results indicate that VHL elongin BC protein complex components other than VHL could be important for PCC tumorigenesis and merit further investigation

    Justifying the Special Theory of Relativity with Unconceived Methods

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    Many realists argue that present scientific theories will not follow the fate of past scientific theories because the former are more successful than the latter. Critics object that realists need to show that present theories have reached the level of success that warrants their truth. I reply that the special theory of relativity has been repeatedly reinforced by unconceived scientific methods, so it will be reinforced by infinitely many unconceived scientific methods. This argument for the special theory of relativity overcomes the critics’ objection, and has advantages over the no-miracle argument and the selective induction for it

    Corals record persistent multidecadal SST variability in the Atlantic Warm Pool since 1775 AD

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    Author Posting. © American Geophysical Union, 2012. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 27 (2012): PA3231, doi:10.1029/2012PA002313.Accurate low-latitude sea surface temperature (SST) records that predate the instrumental era are needed to put recent warming in the context of natural climate variability and to evaluate the persistence of lower frequency climate variability prior to the instrumental era and the possible influence of anthropogenic climate change on this variability. Here we present a 235-year-long SST reconstruction based on annual growth rates (linear extension) of three colonies of the Atlantic coral Siderastrea siderea sampled at two sites on the northeastern Yucatan Peninsula, Mexico, located within the Atlantic Warm Pool (AWP). AWP SSTs vary in concert the Atlantic Multidecadal Oscillation (AMO), a basin-wide, quasiperiodic (∼60–80 years) oscillation of North Atlantic SSTs. We demonstrate that the annual linear growth rates of all three coral colonies are significantly inversely correlated with SST. We calibrate annual linear growth rates to SST between 1900 and 1960 AD. The linear correlation coefficient over the calibration period is r = −0.77 and −0.66 over the instrumental record (1860–2008 AD). We apply our calibration to annual linear growth rates to extend the SST record to 1775 AD and show that multidecadal SST variability has been a persistent feature of the AWP, and likely, of the North Atlantic over this time period. Our results imply that tropical Atlantic SSTs remained within 1°C of modern values during the past 225 years, consistent with a previous reconstruction based on coral growth rates and with most estimates based on the Mg/Ca of planktonic foraminifera from marine sediments.Funding was provided by a scholarship to L.F.V.B. from ‘Consejo Nacional de Ciencia y Tecnología’ (CONACyT-Mexico), by CONACyT projects 104358 and 23749 to P.B., and by NSF OCE-0926986 to A.L.C. and D.W.O.2013-03-2

    In Defense of the Epistemic Imperative

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    Sample (2015) argues that scientists ought not to believe that their theories are true because they cannot fulfill the epistemic obligation to take the diachronic perspective on their theories. I reply that Sample’s argument imposes an inordinately heavy epistemic obligation on scientists, and that it spells doom not only for scientific theories but also for observational beliefs and philosophical ideas that Samples endorses. I also delineate what I take to be a reasonable epistemic obligation for scientists. In sum, philosophers ought to impose on scientists only an epistemic standard that they are willing to impose on themselves

    Aberrant Expression of Pseudogene-Derived lncRNAs as an Alternative Mechanism of Cancer Gene Regulation in Lung Adenocarcinoma

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    Transcriptome sequencing has led to the widespread identification of long non-coding RNAs (lncRNAs). Subsequently, these genes have been shown to hold functional importance in human cellular biology, which can be exploited by tumors to drive the hallmarks of cancer. Due to the complex tertiary structure and unknown binding motifs of lncRNAs, there is a growing disparity between the number of lncRNAs identified and those that have been functionally characterized. As such, lncRNAs deregulated in cancer may represent critical components of cancer pathways that could serve as novel therapeutic intervention points. Pseudogenes are non-coding DNA sequences that are defunct relatives of their protein-coding parent genes but retain high sequence similarity. Interestingly, certain lncRNAs expressed from pseudogene loci have been shown to regulate the protein-coding parent genes of these pseudogenes in trans particularly because of this sequence complementarity. We hypothesize that this phenomenon occurs more broadly than previously realized, and that aberrant expression of lncRNAs overlapping pseudogene loci provides an alternative mechanism of cancer gene deregulation. Using RNA-sequencing data from two cohorts of lung adenocarcinoma, each paired with patient-matched non-malignant lung samples, we discovered 104 deregulated pseudogene-derived lncRNAs. Remarkably, many of these deregulated lncRNAs (i) were expressed from the loci of pseudogenes related to known cancer genes, (ii) had expression that significantly correlated with protein-coding parent gene expression, and (iii) had lncRNA protein-coding parent gene expression that was significantly associated with survival. Here, we uncover evidence to suggest the lncRNA-pseudogene-protein-coding gene axis as a prominent mechanism of cancer gene regulation in lung adenocarcinoma, and highlights the clinical utility of exploring the non-coding regions of the cancer transcriptome
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