Обучение академическому письму: проблемы и решения

Обозначены основные проблемы, с которыми сталкиваются преподаватели и студенты при внедрении курса "Академическое письмо". Проведен анализ письменных работ студентов на английском языке, описаны трудности, которые испытывают студенты при их написани

Hsp90 governs dispersion and drug resistance of fungal biofilms

Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving clinical outcome in the treatment of biofilm infections

Spatial Distribution, Air-Water Fugacity Ratios and Source Apportionment of Polychlorinated Biphenyls in the Lower Great Lakes Basin

Polychlorinated biphenyls (PCBs) continue to be contaminants of concern across the Great Lakes. It is unclear whether current concentrations are driven by ongoing primary emissions from their original uses, or whether ambient PCBs are dominated by their environmental cycling. Freely dissolved PCBs in air and water were measured using polyethylene passive samplers across Lakes Erie and Ontario during summer and fall, 2011, to investigate their spatial distribution, determine and apportion their sources and to asses their air–water exchange gradients. Average gaseous and freely dissolved ∑29 PCB concentrations ranged from 5.0 to 160 pg/m3 and 2.0 to 55 pg/L respectively. Gaseous concentrations were significantly correlated (R2 = 0.80) with the urban area within a 3−20 km radius. Fugacity ratios indicated that the majority of PCBs are volatilizing from the water thus acting as a secondary source for the atmosphere. Dissolved PCBs were probably linked to PCB emissions from contaminated sites and areas of concern. Positive matrix factorization indicated that although volatilized Aroclors (gaseous PCBs) and unaltered Aroclors (dissolved PCBs) dominate in some samples, ongoing non-Aroclor sources such as paints/pigments (PCB 11) and coal/wood combustion showed significant contributions across the lower Great Lakes. Accordingly, control strategies should give further attention to PCBs emitted from current use sources

Spatial Kramers-Kronig relations and the reflection of waves

Copyright © 2015, Rights Managed by Nature Publishing GroupAuthor version of article. The version of record is available from the publisher via DOI: 10.1038/nphoton.2015.106When a planar dielectric medium has a permittivity profile that is an analytic function in the upper or lower half of the complex position plane x=x'+ix'' then the real and imaginary parts of its permittivity are related by the spatial Kramers-Kronig relations. We find that such a medium will not reflect radiation incident from one side, whatever the angle of incidence. Using the spatial Kramers-Kronig relations, one can derive a real part of a permittivity profile from some given imaginary part (or vice versa) such that the reflection is guaranteed to be zero. This result is valid for both scalar and vector wave theories and may have relevance for designing materials that efficiently absorb radiation or for the creation of a new type of anti-reflection surface.Engineering and Physical Sciences Research Council (EPSRC

SPARC REport No. 7

peer reviewedThe Montreal Protocol (MP) controls the production and consumption of carbon tetrachloride (CCl4 or CTC) and other ozone-depleting substances (ODSs) for emissive uses. CCl4 is a major ODS, accounting for about 12% of the globally averaged inorganic chlorine and bromine in the stratosphere, compared to 14% for CFC-12 in 2012. In spite of the MP controls, there are large ongoing emissions of CCl4 into the atmosphere. Estimates of emissions from various techniques ought to yield similar numbers. However, the recent WMO/UNEP Scientific Assessment of Ozone Depletion [WMO, 2014] estimated a 2007-2012 CCl4 bottom-up emission of 1-4 Gg/year (1-4 kilotonnes/year), based on country-by-country reports to UNEP, and a global top-down emissions estimate of 57 Gg/ year, based on atmospheric measurements. This 54 Gg/year difference has not been explained. In order to assess the current knowledge on global CCl4 sources and sinks, stakeholders from industrial, governmental, and the scientific communities came together at the “Solving the Mystery of Carbon Tetrachloride” workshop, which was held from 4-6 October 2015 at Empa in Dübendorf, Switzerland. During this workshop, several new findings were brought forward by the participants on CCl4 emissions and related science. • Anthropogenic production and consumption for feedstock and process agent uses (e.g., as approved solvents) are reported to UNEP under the MP. Based on these numbers, global bottom-up emissions of 3 (0-8) Gg/year are estimated for 2007-2013 in this report. This number is also reasonably consistent with this report’s new industry-based bottom-up estimate for fugitive emissions of 2 Gg/year. • By-product emissions from chloromethanes and perchloroethylene plants are newly proposed in this report as significant CCl4 sources, with global emissions estimated from these plants to be 13 Gg/year in 2014. • This report updates the anthropogenic CCl4 emissions estimation as a maximum of ~25 Gg/year. This number is derived by combining the above fugitive and by-product emissions (2 Gg/year and 13 Gg/year, respectively) with 10 Gg/year from legacy emissions plus potential unreported inadvertent emissions from other sources. • Ongoing atmospheric CCl4 measurements within global networks have been exploited for assessing regional emissions. In addition to existing emissions estimates from China and Australia, the workshop prompted research on emissions in the U.S. and Europe. The sum of these four regional emissions is estimated as 21±7.5a Gg/year, but this is not a complete global accounting. These regional top-down emissions estimates also show that most of the CCl4 emissions originate from chemical industrial regions, and are not linked to major population centres. • The total CCl4 lifetime is critical for calculating top-down global emissions. CCl4 is destroyed in the stratosphere, oceans, and soils, complicating the total lifetime estimate. The atmospheric lifetime with respect to stratospheric loss was recently revised to 44 (36-58) years, and remains unchanged in this report. New findings from additional measurement campaigns and reanalysis of physical parameters lead to changes in the ocean lifetime from 94 years to 210 (157-313) years, and in the soil lifetime from 195 years to 375 (288-536) years. • These revised lifetimes lead to an increase of the total lifetime from 26 years in WMO [2014] to 33 (28-41) years. Consequently, CCl4 is lost at a slower rate from the atmosphere. With this new total lifetime, the global top-down emissions calculation decreases from 57 (40-74) Gg/year in WMO [2014] to 40 (25-55) Gg/year. This estimate is relatively consistent with the independent gradient top-down emissions of 30 (25-35) Gg/year, based upon differences between atmospheric measurements of CCl4 in the Northern and Southern Hemispheres. In addition, this new total lifetime implies an upper limit of 3-4 Gg/year of natural emissions, based upon newly reported observations of old air in firn snow. These new CCl4 emissions estimates from the workshop make considerable progress toward closing the emissions discrepancy. The new industrial bottom-up emissions estimate (15 Gg/year total) includes emissions from chloromethanes plants (13 Gg/year) and feedstock fugitive emissions (2 Gg/year). When combined with legacy emissions and unreported inadvertent emissions, this could be up to 25 Gg/year. Top-down emissions estimates are: global 40 (25-55) Gg/year, gradient 30 (25-35) Gg/year, and regional 21 (14-28) Gg/year. While the new bottom-up value is still less than the aggregated top-down values, these estimates reconcile the CCl4 budget discrepancy when considered at the edges of their uncertainties

The novel homozygous KCNJ10 c.986T>C (p.(Leu329Pro)) variant is pathogenic for the SeSAME/EAST homologue in Malinois dogs.

SeSAME/EAST syndrome is a multisystemic disorder in humans, characterised by seizures, sensorineural deafness, ataxia, developmental delay and electrolyte imbalance. It is exclusively caused by homozygous or compound heterozygous variations in the KCNJ10 gene. Here we describe a similar syndrome in two families belonging to the Malinois dog breed, based on clinical, neurological, electrodiagnostic and histopathological examination. Genetic analysis detected a novel pathogenic KCNJ10 c.986T>C (p.(Leu329Pro)) variant that is inherited in an autosomal recessive way. This variant has an allele frequency of 2.9% in the Belgian Malinois population, but is not found in closely related dog breeds or in dog breeds where similar symptoms have been already described. The canine phenotype is remarkably similar to humans, including ataxia and seizures. In addition, in half of the dogs clinical and electrophysiological signs of neuromyotonia were observed. Because there is currently no cure and treatment is nonspecific and unsatisfactory, this canine translational model could be used for further elucidating the genotype/phenotype correlation of this monogenic multisystem disorder and as an excellent intermediate step for drug safety testing and efficacy evaluations before initiating human studies

Levels of (1→3)-β-D-glucan, Candida mannan and Candida DNA in serum samples of pediatric cancer patients colonized with Candida species

<p>Abstract</p> <p>Background</p> <p>Surveillance cultures may be helpful in identifying patients at increased risk of developing invasive candidiasis. However, only scant information exists on the effect of <it>Candida </it>colonization on serum levels of diagnostic biomarkers. This prospective surveillance study determined the extent of <it>Candida </it>colonization among pediatric cancer patients and its possible impact on serum levels of (1-3)-β-D-glucan (BDG), <it>Candida </it>mannan and <it>Candida </it>DNA.</p> <p>Methods</p> <p>A total of 1075 swabs originating from oropharynx (n = 294), nostrils (n = 600), rectum (n = 28), groin (n = 50), ear (n = 54), and axilla (n = 49) of 63 pediatric cancer patients were cultured for the isolation of <it>Candida </it>spp. Patients yielding <it>Candida </it>spp. from any sites were considered as colonized. Serum samples were collected from patients at the time of first surveillance culture for detection of BDG by Fungitell kit and <it>Candida </it>mannan by Platelia <it>Candida </it>Ag. <it>Candida </it>DNA was detected by using panfungal primers and identification was carried out by using species-specific primers and DNA sequencing.</p> <p>Results</p> <p>Seventy-five (7.6%) swab cultures from 35 (55.5%) patients yielded <it>Candida </it>spp. These isolates included <it>C. albicans </it>(n = 62), <it>C. dubliniensis </it>(n = 8), <it>C. glabrata </it>and <it>C. tropicalis </it>(n = 2 each) and <it>C. krusei </it>(n = 1). Eleven patients were colonized at three or more sites. Eight of 36 serum samples from 6 colonized patients yielded BDG values higher than the currently recommended cut-off value of ≥80 pg/ml. However, none of the serum samples yielded <it>Candida </it>mannan levels ≥0.5 ng/ml and PCR test for <it>Candida </it>DNA was also negative in all the serum samples of colonized patients. During the study period, only two colonized patients subsequently developed candidemia due to <it>C. tropicalis</it>. Besides positive blood cultures, <it>C. tropicalis </it>DNA, BDG and <it>Candida </it>mannan were also detected in serum samples of both the patients.</p> <p>Conclusions</p> <p>The present study demonstrates that while mucosal colonization with <it>Candida </it>species in pediatric cancer patients is common, it does not give rise to diagnostically significant levels of <it>Candida </it>mannan or <it>Candida </it>DNA in serum specimens. However, BDG values may be higher than the cut-off value in some pediatric patients without clinical evidence of invasive <it>Candida </it>infection. The study suggests the utility of <it>Candida </it>mannan or <it>Candida </it>DNA in the diagnosis of invasive candidiasis, however, the BDG levels in pediatric cancer subjects should be interpreted with caution.</p

Selenium status is positively associated with bone mineral density in healthy aging European men

Objective It is still a matter of debate if subtle changes in selenium (Se) status affect thyroid function tests (TFTs) and bone mineral density (BMD). This is particularly relevant for the elderly, whose nutritional status is more vulnerable. Design and Methods We investigated Se status in a cohort of 387 healthy elderly men (median age 77 yrs; inter quartile range 75-80 yrs) in relation to TFTs and BMD. Se status was determined by measuring both plasma selenoprotein P (SePP) and Se. Results The overall Se status in our population was low normal with only 0.5% (2/387) of subjects meeting the criteria for Se deficiency. SePP and Se levels were not associated with thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroxine (T4), triiodothyronine (T3) or reverse triiodothyronine (rT3) levels. The T3/T4 and T3/rT3 ratios, reflecting peripheral metabolism of thyroid hormone, were not associated with Se status either. SePP and Se were positively associated with total BMD and femoral trochanter BMD. Se, but not SePP, was positively associated with femoral neck and ward's BMD. Multivariate linear analyses showed that these associations remain statistically significant in a model including TSH, FT4, body mass index, physical performance score, age, smoking, diabetes mellitus and number of medication use. Conclusion Our study demonstrates that Se status, within the normal European marginally supplied range, is positively associated with BMD in healthy aging men, independent of thyroid function. Thyroid function tests appear unaffected by Se status in this population

Perspectives on care and communication involving incurably ill Turkish and Moroccan patients, relatives and professionals: a systematic literature review

<p>Abstract</p> <p>Background</p> <p>Our aim was to obtain a clearer picture of the relevant care experiences and care perceptions of incurably ill Turkish and Moroccan patients, their relatives and professional care providers, as well as of communication and decision-making patterns at the end of life. The ultimate objective is to improve palliative care for Turkish and Moroccan immigrants in the Netherlands, by taking account of socio-cultural factors in the guidelines for palliative care.</p> <p>Methods</p> <p>A systematic literature review was undertaken. The data sources were seventeen national and international literature databases, four Dutch journals dedicated to palliative care and 37 websites of relevant national and international organizations. All the references found were checked to see whether they met the structured inclusion criteria. Inclusion was limited to publications dealing with primary empirical research on the relationship between socio-cultural factors and the health or care situation of Turkish or Moroccan patients with an oncological or incurable disease. The selection was made by first reading the titles and abstracts and subsequently the full texts. The process of deciding which studies to include was carried out by two reviewers independently. A generic appraisal instrument was applied to assess the methodological quality.</p> <p>Results</p> <p>Fifty-seven studies were found that reported findings for the countries of origin (mainly Turkey) and the immigrant host countries (mainly the Netherlands). The central themes were experiences and perceptions of family care, professional care, end-of-life care and communication. Family care is considered a duty, even when such care becomes a severe burden for the main female family caregiver in particular. Professional hospital care is preferred by many of the patients and relatives because they are looking for a cure and security. End-of-life care is strongly influenced by the continuing hope for recovery. Relatives are often quite influential in end-of-life decisions, such as the decision to withdraw or withhold treatments. The diagnosis, prognosis and end-of-life decisions are seldom discussed with the patient, and communication about pain and mental problems is often limited. Language barriers and the dominance of the family may exacerbate communication problems.</p> <p>Conclusions</p> <p>This review confirms the view that family members of patients with a Turkish or Moroccan background have a central role in care, communication and decision making at the end of life. This, in combination with their continuing hope for the patient’s recovery may inhibit open communication between patients, relatives and professionals as partners in palliative care. This implies that organizations and professionals involved in palliative care should take patients’ socio-cultural characteristics into account and incorporate cultural sensitivity into care standards and care practices<it>.</it></p