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We present CHARMM-compatible force field parameters for a series of fluorescent dyes from the Alexa, Atto, and Cy families, commonly used in Förster resonance energy transfer (FRET) experiments. These dyes are routinely used in experiments to resolve the dynamics of proteins and nucleic acids at the nanoscale. However, little is known about the accuracy of the theoretical approximations used in determining the dynamics from the spectroscopic data. Molecular dynamics simulations can provide valuable insights into these dynamics at an atomistic level, but this requires accurate parameters for the dyes. The complex structure of the dyes and the importance of this in determining their spectroscopic properties mean that parameters generated by analogy to existing parameters do not give meaningful results. Through validation relative to quantum chemical calculation and experiments, the new parameters are shown to significantly outperform those that can be generated automatically, giving better agreement in both the charge distributions and structural properties. These improvements, in particular with regard to orientation of the dipole moments on the dyes, are vital for accurate simulation of FRET processes.

Single-molecule Förster Resonance Energy Transfer (smFRET) is a powerful technique capable of resolving both relative and absolute distances within and between structurally dynamic biomolecules. High instrument costs, and a lack of open-source hardware and acquisition software have limited smFRET’s broad application by non-specialists. Here, we present the smfBox, a cost-effective confocal smFRET platform, providing detailed build instructions, open-source acquisition software, and full validation, thereby democratising smFRET for the wider scientific community.

Human flap endonuclease-1 (hFEN1) catalyzes the divalent metal ion-dependent removal of single-stranded DNA protrusions known as flaps during DNA replication and repair. Substrate selectivity involves passage of the 5′-terminus/flap through the arch and recognition of a single nucleotide 3′-flap by the α2–α3 loop. Using NMR spectroscopy, we show that the solution conformation of free and DNA-bound hFEN1 are consistent with crystal structures; however, parts of the arch region and α2–α3 loop are disordered without substrate. Disorder within the arch explains how 5′-flaps can pass under it. NMR and single-molecule FRET data show a shift in the conformational ensemble in the arch and loop region upon addition of DNA. Furthermore, the addition of divalent metal ions to the active site of the hFEN1–DNA substrate complex demonstrates that active site changes are propagated via DNA-mediated allostery to regions key to substrate differentiation. The hFEN1–DNA complex also shows evidence of millisecond timescale motions in the arch region that may be required for DNA to enter the active site. Thus, hFEN1 regional conformational flexibility spanning a range of dynamic timescales is crucial to reach the catalytically relevant ensemble.

In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.

In a time of continuing urbanization, there is an increasing focus on developing attractive and healthy urban environments. Green spaces, ranging from woodlands and parks to allotment gardens and green roofs, provide a range of ecosystem services that contribute to better cities (Lovell and Taylor, 2013). The Green Infrastructure and Urban Biodiversity for Sustainable Urban Development and the Green Economy project (GREEN SURGE in brief), funded under the EU’s 7th Framework Programme for research, will identify, develop and test ways of linking green spaces, biodiversity, people and the green economy in order to meet the major urban challenges related to land use conflicts, climate change adaptation, demographic changes and human health and well being. The contents of this report are based on work conducted in Work Package 6, one of the eight Work Packages of GREEN SURGE. Work Package 6 focuses on governance arrangements for urban green spaces. In this report, we discuss the findings of the GREEN SURGE Work Package 6 Tier 1 research on identifying and conceptualising innovative participatory governance arrangements in regards to the management of urban green infrastructure.

Code-switching in the classroom is known to take place across a wide range of subjects in multilingual settings in Africa and, indeed, throughout the world; yet it is often regarded pejoratively by some educational policy makers. This article looks at code-switching (CS) in Botswana’s senior secondary schools within the context of the country’s language-in-education policy, which states that English is the official language of learning and teaching while Setswana is the national language used for identity, unity and national pride. The data are derived from an ethnographic study conducted at four high schools in the north-eastern part of the country, which is uniquely multilingual. The findings indicate that code-switching from English to Setswana is quite prevalent in content subjects, and is used as a pedagogic resource to clarify the knowledge of the subject matter and to reduce the social distance between the teacher and learners. From the findings, it is suggested that code-switching in ESL classrooms in Botswana should be recognized not only as a communicative strategy for instruction, but also as a way of creating classroom warmth and friendliness.

The purpose of this study is to find out the academic literacy skills in English of ESL first year humanities students from their own point of view. It is motivated by the fact that many lecturers at this university (and perhaps at many other universities elsewhere) often complain about the limited academic literacy skills of their students, especially those who use English as an additional or non-native language. Using both quantitative and qualitative research methods, the views and final examination essays of thirty conveniently sampled students were analyzed. The findings show that the majority of the students rated many of their academic literacy skills ‘average’. In terms of their writing skills, the results indicate that the majority of the students have pragmatic competence which enables them to communicate their intended meaning reasonably well; but what they lack mainly is organizational competence, i.e. the ability to write ideas fluently and accurately. To help the students overcome some of their academic literacy limitations, it is suggested that teachers should first try to understand the students’ practices, and to give written work that fosters a sense of ownership, self-reflection and personal engagement.

This article discusses the controversial concept of the “native speaker” of English within the context of the language policy on higher education of not only Southern Africa in general, but also of many other bi- or multilingual countries that are faced with the problem of choosing a language that can be used for higher education. First, the article analyzes in some detail the different criteria used for defining a native speaker of English. It shows that many of the common assumptions are either hollow, half-truths or are deliberately intended to reinforce social, political, economic and educational exclusivity. The article then goes on to show how the notion of the “native speaker” of English affects ESL teaching and learning. In each case, it is argued that an insistence on “native speaker” norms, such as the use of “standard” English, suffocates the growth of regional varieties that have characterized, over many generations, the accommodative nature of English. The remaining part of the article is devoted to suggesting the ways and means of tackling English language learning problems in order to enhance the students\' academic literacy skills. The article concludes by proposing that the main challenge in our current language discourse is to design a vibrant learning and teaching curriculum that can produce an academic intelligentsia that are capable of competing globally. Keywords : native speaker, acquisition, Standard English; dialect, mother tongue, critical period; first language, second language; bilingual; multilingual, competence Journal for Language Teaching Vol. 39(1) 2005: 18-33

The historical development of the insurance industry's role in efforts to prevent industrial accidents and occupational disease will be discussed. The various approaches that have evolved include fire insurance, casuality insurance, and compensation for occupational diseases. The basic approach used in insurance programs involved with occupational disease is to identify the toxic material to which employees are exposed, recommend engineering controls to reduce the exposure, and suggest a medical surveillance program. The insurance industry's efforts in industrial hygiene are also described.

Evaluation was made of the present condition of a girl, a boy and a woman subjected to choledochocystoduodenostomy eleven, eight and one and a half years previously. At the time of operation their ages were five and one-half, six and one-half and thirty-one years, respectively. Each patient had complained of episodes of pain in the upper part of the abdomen associated with nausea and vomiting. The boy also had had subclinical jaundice during his attacks of pain. None of the patients had a palpable abdominal mass on physical examination. During the eleven years since her operation, the girl has had no symptoms except for three brief episodes of subcostal discomfort which occurred in January, 1963 and may have been due to cholangitis. The boy, in the eight years following his operation, has also been well except for three bouts of abdominal pain, fever and elevated leukocyte count which occurred late in 1962. These may have been due to cholangitis from partial obstruction of the anastomotic opening since each bout followed ingestion of nut meats. On eliminating nut meats from his diet, he has had no further trouble. The woman has remained asymptomatic. Proximity of the common bile duct to the duodenum makes choledochocystoduodenostomy a simpler and safer operation than others that have been advocated for treatment of congenital cystic dilatation of the common bile duct. Unless it is diseased, the gallbladder is best not removed.