Journal articles on the topic 'Heavy gale'

Coastal areas are home to billions of people and assets that are prone to natural disasters and climate change. In this study, we established a disaster network to assess the multi-hazards (gale and heavy rain) of typhoon disasters, specifically Typhoon Mangkhut of 2018 in coastal China, by applying the methodology of a bipartite network in both time dimension and spatial dimension. In this network, the edge set and adjacent matrix are based on the connection between an hour and a city with a multi-hazards impact that includes gales and heavy rain. We analyze the characteristics and structure of this disaster network and assess the multi-hazards that arose from Typhoon Mangkhut in different areas. The result shows that there are 14 cities in the core area and 21 cities in the periphery area, based on core–periphery classification in the disaster network. Although more damage area belongs to the periphery area, the percentage of the population affected by the typhoon and direct economic loss in GDP in the core area was 69.68% and 0.22% respectively, which is much higher than in the periphery area (55.58% and 0.06%, respectively) The core area suffered more from multi-hazards and had more disaster loss. This study shows that it is feasible to assess multiple hazards with a disaster network based on the bipartite network.

In Heavy Weather Sailing, Adlard Coles defines a survival storm, as distinct from a full gale, as those conditions in which, the wind at Force 10 or above and perhaps gusting at hurricane strength, wind and sea become the masters; there is little the unfortunate mariner can do. It is impossible for anyone in a small boat in the middle of an ocean storm to judge wind-speed or sea-state accurately, if only because the height of eye will be too low to see enough of the sea surface. However, an experienced observer will be able to distinguish between storm-force and gale-force winds and if he knows his craft well enough he will sense when she has become at the mercy of the seas. In precisely these terms I believe Jester to have experienced a survival storm in the vicinity of 48° 30′ N., 12° 30′ W. on 1 August 1986. She was on her way back from Nova Scotia to Plymouth, some 25 days out, 250 miles from her destination. It was her thirteent transatlantic crossing.

Objective:This review aimed to explore recent published literature, research and practice in managing breast cancer wounds with a specific focus on the potential values of honey in managing the wounds.Methods:Ten databases were searched (CINAHL, EBSCOhost, ProQuest, Google Scholar, Wiley Interscience, Science Direct, Blackwell Synergy, Liebert Online, Internurse, and Gale Cengage) using the search terms ‘fungating wound’ OR ‘malignant wound’, ‘breast cancer wounds’ AND ‘honey’ AND ‘Indonesia’. The search was limited from period of 2006 to 2016, to English and Indonesian language, and only full text articles were included. Reference lists of relevant articles were also hand searched.Results: The search identified twelve articles that met the search criteria. An article published before 2006 was also included on the basis of its relevance. All articles were written in English. Publications have indicated that a malignant wound represents a cluster of symptoms such as malodor, heavy exudate, pain, bleeding, and various psychosocial issues.In order to stabilize and prevent wound deterioration, the physical and bioactive properties of honey may have potentials to be applied as a single treatment in primary wound dressings to manage offensive odor and heavy exudate. Conclusion: Further research to study native Indonesian honeys’ properties will be beneficial to assist with practice decisions.

Abstract. The baroclinic depression that affected the area of Cyprus during the cold period, between 28 and 29 January 2008 was thoroughly studied and is presented in the present paper. A small perturbation on a northwesterly flow to the north of Cyprus has initiated the generation of the depression and in 24 h this developed into a deep baroclinic system. This depression was associated with intense weather phenomena, such as heavy thunderstorms with hail and near gale force winds. Strong cold advection resulted in a significant temperature decrease; precipitation even in lower altitudes was in the form of snow, while the accumulated rainfall corresponded to the 25% of the monthly normal. January 2008 is considered as a dry month, despite the fact that, on the average, January is considered as the wettest month of the year. In this study, the evolution and development of the depression was investigated from synoptic, dynamic, energetic and thermodynamic perspectives, in order to enhance our knowledge on the life cycle and behaviour of similar depressions over the area with extreme characteristics.

Abstract. In August 2002, Typhoon RUSA hit Korea with severe gale and storm, causing extensive damage throughout the whole country and especially in the Gangneung area. Even on a single day, Typhoon RUSA recorded up to 879.5 mm of rainfall in the Gangneung area. Quantitative and qualitative analyses of the scale of Typhoon RUSA are performed in this study. Most of the inland affected by RUSA in the Korean Peninsula recorded heavy rainfall, equivalent to a return period of more than 200 years. Especially, rainfall of 24 h duration exceeded the maxima observed so far. Although areal rainfall showed a rapidly decreasing trend with increasing area, it reached 96 percent of the existing PMP within a 2000 km2 area and recorded the maximum observed value of Korea according to a DAD analysis of rainfall. Re-estimated PMP values obtained from a hydro-meteorological approach compared with existing PMP estimates revealed a discrepancy between the two values, which showed that re-estimated PMP values of 12 to 24 h duration within 2000 km2 exceeded the existing PMP estimates of Korea. Therefore, modification of the existing PMP is required, which is used as a design hydrological variable of hydraulic structure.

A subtropical squall line moved from Guangxi to Guangdong province in South China on 23-24 April 2007, which resulted in gale and heavy precipitation. The three-dimensional (3D) wind field of the squall line in its mature period was retrieved by Guangzhou-Shenzhen dual-Doppler data. The 3D conceptual model of this squall line was proposed. On the horizontal plane, the storm-relative front-to-rear inflow prevailed at the lower altitudes of the leading edge. The rear-to-front cold inflow in the stratiform region was observed below 3 km height, which enhanced the convergence in the convective region. At the middle altitudes of the squall line, the front-to-rear horizontal flow prevailed. Strong updrafts were observed at the lower and middle altitudes of the leading edge. Some convergence centers were located at the lower altitudes of the convective region. Furthermore, the storm-relative flow in the vertical cross-section perpendicular to the squall line was revealed. The front-to-rear warm flow extended from the surface to 7.5 km altitude at the leading edge. Above it, part of the front-to-rear inflow blew upward and then forward, and the other part of the inflow blew backward. The descending rear-to-front cold flow was only seen below 3 km height in the stratiform region.

East Coast Lows (ECLs) are intense low-pressure systems which occur over the subtropical east coasts of southern and northern hemisphere continents. ECLs are typically associated with gale force winds, large seas, storm surges, heavy rainfall and flooding. While ECL impacts are typically seen as negative the rainfall associated with ECLs is also very important for urban water security within the heavily populated eastern seaboard of Australia (ESA). This study investigates historical ECLs to gain insights into the timing, frequency, intensity and location of ECL occurrence as well as the magnitude and spatial extent of ECL impacts on rainfall. The different characteristics and impacts associated with different ECL sub-types are highlighted and it is proposed that this spatial and temporal variability in ECL behaviour at least partially explains why the ESA is hydroclimatically different to the rest of Australia and why different locations within the ESA have such different rainfall patterns—and therefore different levels of flood and drought risk. The-se insights are critical to the objectives of the New South Wales government funded Eastern Seaboard Climate Change Initiative (ESCCI), in particular Project 5 which focuses on the water security impacts of ECLs. The results of this work will be used to produce climate-informed stochastic daily rainfall simulations that are more realistic than existing stochastic rainfall simulation methods at preserving the statistics important for catchment-scale hydrology (e.g. clustering of extreme events, long-term persistence, frequency/duration/magnitude of wet and dry spells). These simulated rainfall sequences, that incorporate the spatial and temporal hydroclimatic variability caused by ECLs and other climate phenomena, are important inputs into the hydrological models used to determine current and future urban water security within the ESA.

The developing nervous system is vulnerable to heavy metal exposure, which can cause alterations in neuronal and glial cells in the brain. Thus, heavy metals such as mercury and lead reduce myelin galactocerebroside (GalC) synthesis, and increase the ratio of non-hydroxylated fatty acids to hydroxylated fatty acids (GalC-N:GalC-OH) in the GalC molecules in newborn rats. This study investigated the effect of lead on the expression of myelin components by the myelin-forming oligodendroglial cells (OG) in vitro. Primary cultures of mixed glial cells from brains of newborn rats were continuously exposed to triethyllead (TEL; 1nM, 10nM, 50nM and 100nM) for 3 weeks, one week after seeding. The first morphological alteration observed was an increased proliferation of OG in cultures exposed to 10nM TEL. Biochemical analyses showed up-regulation of the enzymes, 2'3’-cyclic nucleotide 3’-phosphodiesterase and 5’-nucleotidase. GalC synthesis was also stimulated, and the ratio GalC-N:GalC-OH was reduced. The results indicate that TEL stimulates the differentiation and maturation of OG in cultures, which suggests that the alterations induced by heavy metals in newborn rats are not due to interference with the OG maturation.

Abstract. Tropical cyclones (TCs) result in widespread damage associated with strong winds, heavy rainfall and storm surge. TC Yasi was one of the most powerful TCs to impact the Queensland coast since records began. Prior to Yasi, the SSTs in the Coral Sea were higher than average by 1–2 ∘C, primarily due to the 2010/2011 La Niña event. In this study, a conceptually simple idealised sensitivity analysis is performed using a high-resolution regional model to gain insight into the influence of SST on the track, size, intensity and associated rainfall of TC Yasi. A set of nine simulations with uniform SST anomalies of between −4 and 4 ∘C applied to the observed SSTs are analysed. The resulting surface winds and pressure are used to force a barotropic storm surge model to examine the influence of SST on the associated storm surge of TC Yasi. An increase in SST results in an increase in intensity, precipitation and integrated kinetic energy of the storm; however, there is little influence on track prior to landfall. In addition to an increase in precipitation, there is a change in the spatial distribution of precipitation as the SST increases. Decreases in SSTs result in an increase in the radius of maximum winds due to an increase in the asymmetry of the storm, although the radius of gale-force winds decreases. These changes in the TC characteristics also lead to changes in the associated storm surge. Generally, cooler (warmer) SSTs lead to reduced (enhanced) maximum storm surges. However, the increase in surge reaches a maximum with an increase in SST of 2 ∘C. Any further increase in SST does not affect the maximum surge but the total area and duration of the simulated surge increases with increasing upper ocean temperatures. A large decrease in maximum storm surge height occurs when a negative SST anomaly is applied, suggesting if TC Yasi had occurred during non-La Niña conditions the associated storm surge may have been greatly diminished, with a decrease in storm surge height of over 3 m when the SST is reduced by 2 ∘C. In summary, increases in SST lead to an increase in the potential destructiveness of TCs with regard to intensity, precipitation and storm surge, although this relationship is not linear.

Abstract Gala Lake National Park that has an international importance is one of the most important wetland ecosystems for Turkey. As same as many aquatic habitats, Gala Lake is under a significant anthropogenic pressure originated from agricultural activities conducted around the lake and from industrial discharges by means of Ergene River. The aim of this study was to evaluate the sediment quality of Gala Lake and Irrigation Canal by investigating some toxic element accumulations (As, B, Ni, Cr, Pb, Cd, Zn and Cu) from a statistical perspective. Pearson Correlation Index (PCI) and Factor Analysis (FA) were applied to detected data in order to determine the associated contaminants and effective factors on the system. Potential Ecological Risk Index (RI) and Biological Risk Index based sediment quality guidelines (mERM-Q) applied to detected data in order to assess the ecological and biological risks of heavy metals in the ecosystem. Also Geographic Information System (GIS) technology was used to make visual explanations by presenting distribution maps of investigated elements. According to the results of PCI, significant positive correlations were recorded among the investigated toxic elements at 0.01 significance level. According to the results of FA, two factors, which were named as “Agricultural Factor” and “Industrial Factor”, explained 86.6% of the total variance. According to the results of Potential Ecological Risk Index, cadmium was found to be the highest risk factor and according to results of Biological Risk Index, nickel and chromium were found to be the highest risk factors for Gala Lake and Irrigation Canal. As a result of the present study, it was also determined that heavy metal contents in sediments of Gala Lake National Park reached to critical levels and the system is intensively under effect of agricultural and industrial originated pollution.

Clathrin-mediated vesicular transport is important for normal growth of the yeast Saccharomyces cerevisiae. Previously, we identified a genetic locus (SCD1) that influences the ability of clathrin heavy-chain-deficient (Chc-) yeast cells to survive. With the scd1-v allele, Chc- yeast cells are viable but grow poorly; with the scd1-i allele, Chc- cells are inviable. To identify the SCD1 locus and other genes that can rescue chc1 delta scd1-i cells to viability, a multicopy suppressor selection strategy was developed. A strain of scd1-i genotype carrying the clathrin heavy-chain gene under GAL1 control (GAL1:CHC1) was transformed with a YEp24 yeast genomic library, and colonies that could grow on glucose were selected. Plasmids from six distinct genetic loci, none of which encoded CHC1, were recovered. One of the suppressor loci was shown to be UBI4, the polyubiquitin gene. UBI4 rescues only in high copy number and is not allelic to SCD1. The conjugation of ubiquitin to intracellular proteins can mediate their selective degradation. Since UBI4 is required for survival of yeast cells under stress and is induced during starvation, ubiquitin expression in GAL1:CHC1 cells was examined. After a shift to growth on glucose to repress synthesis of clathrin heavy chains, UBI4 mRNA levels were elevated > 10-fold, whereas the quantity of free ubiquitin declined severalfold relative to that of Chc+ cells. In addition, novel higher-molecular-weight ubiquitin conjugates appeared in clathrin-deficient cells. We suggest that higher levels of ubiquitin are required for turnover of mislocalized or improperly processed proteins that accumulate in the absence of clathrin and that ubiquitin may play a general role in turnover of proteins in the secretory or endocytic pathway.

Clathrin-mediated vesicular transport is important for normal growth of the yeast Saccharomyces cerevisiae. Previously, we identified a genetic locus (SCD1) that influences the ability of clathrin heavy-chain-deficient (Chc-) yeast cells to survive. With the scd1-v allele, Chc- yeast cells are viable but grow poorly; with the scd1-i allele, Chc- cells are inviable. To identify the SCD1 locus and other genes that can rescue chc1 delta scd1-i cells to viability, a multicopy suppressor selection strategy was developed. A strain of scd1-i genotype carrying the clathrin heavy-chain gene under GAL1 control (GAL1:CHC1) was transformed with a YEp24 yeast genomic library, and colonies that could grow on glucose were selected. Plasmids from six distinct genetic loci, none of which encoded CHC1, were recovered. One of the suppressor loci was shown to be UBI4, the polyubiquitin gene. UBI4 rescues only in high copy number and is not allelic to SCD1. The conjugation of ubiquitin to intracellular proteins can mediate their selective degradation. Since UBI4 is required for survival of yeast cells under stress and is induced during starvation, ubiquitin expression in GAL1:CHC1 cells was examined. After a shift to growth on glucose to repress synthesis of clathrin heavy chains, UBI4 mRNA levels were elevated > 10-fold, whereas the quantity of free ubiquitin declined severalfold relative to that of Chc+ cells. In addition, novel higher-molecular-weight ubiquitin conjugates appeared in clathrin-deficient cells. We suggest that higher levels of ubiquitin are required for turnover of mislocalized or improperly processed proteins that accumulate in the absence of clathrin and that ubiquitin may play a general role in turnover of proteins in the secretory or endocytic pathway.

Abstract Thick aluminum (Al) wedge bonds have been widely used in analog microelectronic packages due their lower cost, ease of use and excellent thermal and electrical performance. Reliability of thick Al wedge bonds on bare copper (Cu) leadframes under high temperature aging conditions has not been studied at a fundamental level in the past. This study investigates the reliability performance of Al wedge bonds on bare Cu surfaces under isothermal aging conditions specified by the automotive grade product qualification requirements. Results obtained show that Al/Cu intermetallic formed at the interface is detrimental to the mechanical and electrical package reliability. Plating on the leadframe has been evaluated as a potential mitigation to prevent intermetallic growth and hence improve the overall wedge bond and package reliability under high temperature reliability testing conditions. Significant improvement in the wedge bond and package reliability was achieved by using nickel plating under the wedge bonds. The results presented in this study can be used to design a more robust package capable of meeting stringent automotive grade requirements.

The waters of the North Sea are shallow, and the weather there can be severe. On and around the Dogger Bank sudden gales cause high and heavy seas. The smacksmen of the fishing fleets in the 80s and 90s of the last century were there throughout the year on voyages which could last eight weeks, and their 50–80 ton yawl-rigged smacks were entirely at the mercy of the weather. Their fishing grounds were too far from land for them to run for shelter. They were compelled to ride out the heaviest gales or founder. In 1881 it was estimated that the North Sea fishing population numbered upwards of 12,000, the ‘Short Blue’ fleet alone consisting of 220 smacks crewed by 1,500 men.

Gala apple (Malus domestica Borkh.) trees are prone to heavy cropping but respond to chemical fruitlet thinners to reduce crop load and improve fruit quality. Environmental concerns over the fate of the chemical fruitlet thinner carbaryl is widely acknowledged, but crop load management options are limited. In southern Ontario, Gala trees were treated with new thinning compounds or combinations to determine post-bloom thinning efficacy and resulting fruit quality. Treatments included 6-benzyladenine (6-BA) combined with naphthaleneacetic acid (NAA) or abscisic acid (ABA), and 1-aminocyclopropane-1-carboxylic acid (ACC) alone applied at 9 mm in 2014 and 17 mm in 2015. The treatment NAA + 6-BA produced unacceptably small “pygmy” fruit when applied at 17 mm fruitlet diameter. ABA at 150 and 300 mg L−1 and ACC at 150 mg L−1, when applied at 17 mm fruitlet diameter, resulted in acceptable fruit set, crop load, and quality results in comparison with the carbaryl thinner in 1 yr. The bioregulators ACC and ABA combined with 6-BA showed commercial potential for thinning Gala fruit but require further evaluation.

Huta Gabe Aeksorseang studio is a traditional art studio that helped preserve traditional culture, especially the Batak Toba. The presence of this art studio has stimulated creative economy activities within the region. The problems currently being faced by the Huta Gabe Aeksorseang studio have not been made optimal yet. Products that had been sold nationally but had not well known to many other Indonesian consumers due to there is no product brand. The daily activities of this art gallery cultivate traditional music. This community services is carried out with a focus on solving partner problems by providing appropriate science and technology for the local community, especially for the management of the Studio. The method of making traditional musical instruments is still not optimal so that the resulting sound quality is not correctly produced. Science and technology has been given to partners related to production and marketing techniques that have been carried out. We also provided online marketing strategies to assist the online marketing activities of the Huta Gabe Aeksorseang studio. Technical equipment is also provided to help partners improve product quality and product competitiveness with lower production costs. Heavy equipment such as welding machines in the area makes production costs high. With the help of the equipment provided, partners will be more efficient in production, thereby increasing partner competitiveness.

The present work introduces the role of heterogeneous microstructure in enhancing the nucleation density of reversed austenite. It was found that the novel pre-annealing produced a heterogeneous microstructure consisting of alloying elements-enriched martensite and alloying-depleted intercritical ferrite. The shape of the martensite at the prior austenite grain boundary was equiaxed and acicular at inter-laths. The equiaxed reversed austenite had a K-S orientation with adjacent prior austenite grain, and effectively refined the prior austenite grain that it grew into. The alloying elements-enriched martensite provided additional nucleation sites to form equiaxed reversed austenite at both prior austenite grain boundaries and intragranular inter-lath boundaries during re-austenitization. It was revealed that prior austenite grain size was refined to ~12 μm by pre-annealing and quenching, while it was ~30 μm by conventional quenching. This is a practical way of refining transformation products by refining prior austenite grain size to improve the strength, ductility and low temperature toughness of heavy-gage plate steel.

In 1990 and 1999 two heavy storms struck Europe, the worst gales ever recorded in Switzerland. Millions of cubic metres of standing spruce trees were subsequently attacked by the eight-toothed spruce bark beetle (Ips typographus L.). In Swiss forests, such heavy mass attacks have never been observed before. From 1990 to 1996 standing trees infested by beetles totalled 50% of the spruce timber thrown by the 1990 storm. Logistics sometimes made it impossible to remove all windthrown timber before new generations of beetles emerged. Forest services and forest owners were forced to set priorities. The strained financial situation of many owners and ecological aspects were also reasons for changing forest protection strategies and leaving some storm and bark beetle damaged areas uncleared. In regions with such areas, the amount of subsequent bark beetle attack approximately doubled compared with other regions where storm damages and infestation spots were thoroughly cleared. To answer questions of new risk assessment, projects were started on scolytid behaviour in differently treated regions and in buffer zones.

Turbine blade cooling experiments often use mixtures of air and a heavy gas CO2,SF6 to simulate coolant/mainstream density ratios. If the mixing of the mainstream with the coolant ejected from the blade is of interest, then it may be necessary to determine the spatial distribution of the heavy gas concentration in the flowfield. Commercial analyzers are too slow and have other disadvantages when used for this purpose. To meet this special need, a device has been developed to monitor the heavy gas concentration continuously in a small sample stream by determining the speed of sound in the sample. Together with the temperature of the sample, the information is sufficient to determine the concentration. The device measures the time of propagation for an ultrasonic burst transverse to the stream. The temperature of the gas contained in the device is controlled and measured. Calibration with several gas mixtures (air and CO2,SF6, He) has shown an uncertainty Cmeas−Ctrue of 2 percent over the full concentration range of 0–100 percent for CO2 and SF6. The device is operable in the pressure range from −50 to 100 kPa gage and in the temperature range from 0°C to 40°C. The instrument is rugged and will survive in noisy, turbulent environments. [S0889-504X(00)01202-2]

The harmful impact of the heavy metal lead on human health has been known for years. However, materials that contain lead remain in the environment. Measuring the blood lead level (BLL) is the only way to officially evaluate the degree of exposure to lead. The so-called “safe value” of the BLL seems to unreliably represent the secure threshold for children. In general, lead’s underlying toxicological mechanism remains unclear and needs to be elucidated. Therefore, we developed a novel genetically encoded fluorescence resonance energy transfer (FRET)-based lead biosensor, Met-lead, and applied it to transgenic Drosophila to perform further investigations. We combined Met-lead with the UAS-GAL4 system to the sensor protein specifically expressed within certain regions of fly brains. Using a suitable imaging platform, including a fast epifluorescent or confocal laser-scanning/two-photon microscope with high resolution, we recorded the changes in lead content inside fly brains ex vivo and in vivo and at different life stages. The blood–brain barrier was found to play an important role in the protection of neurons in the brain against damage due to the heavy metal lead, either through food or microinjection into the abdomen. Met-lead has the potential to be a powerful tool for the sensing of lead within living organisms by employing either a fast epi-FRET microscope or high-resolution brain imaging.

Barrel vaults provide effective fire-proof roofing in historic churches, castles, cloisters or halls that look for simple and utilitarian aesthetics, as long as they are strongly connected to sturdy lateral walls and transverse gables, conditions that limit their possibilities for spatial expression. A study of the effect of these conditions was carried out on the pointed vaults of a characteristic group of 15th century Scottish churches. Following earlier measured surveys that showed remarkable geometric integrity, 1/15-scale models of a representative form were made in reinforced plaster that could delay the cracks propagation enough to be monitored. Only the shell was considered, leaving the effect of ribs or diaphragms that hold the heavy flagstone roof for further study. The model was subject to symmetric and asymmetric horizontal spread, which simulated the insufficient containment of not very stiff walls, but included the effect of gable end walls. Cracks formed invariably at an early stage (3% of the span spread), propagating more rapidly and causing early failure at a symmetrical spread (15% of span), while the asymmetrical spread produced diagonal crack patterns across the vault at 33% of the span. Gables provided more stiff areas but eventually caused local detachment at the spread point, at only 5% of the span, with cracks propagating to the back wall and at a higher rate when a less stiff gable was included(13% of span). The results validated an FE model that provided further insight to the performance of the type at displacement and settlement, as exemplified in the case of Bothwell church in Scotland.

A randomized complete block, split-plot experiment with six replicates was established and maintained for the first six fruiting seasons (1999 to 2004) in a high-density apple [Malus sylvestris (L.) Mill var. domestica (Borkh.) Mansf.] orchard on M.9 rootstock planted in Apr. 1998. This report assesses responses to six main-plot fertigation treatments, each containing three tree subplots of five different cultivars (Ambrosia, Cameo, Fuji, Gala, and Silken). Fertigation treatments were a factorial combination of two nitrogen (N) rates and three N application timings. N was applied at low (28 mg N/L) or high (168 mg N/L) concentrations daily at 0 to 4, 4 to 8, or 8 to 12 weeks after full bloom (wafb). Under greater N inputs, all cultivars had increased midsummer leaf and harvested fruit N concentrations, decreased fruit firmness, and in heavy crop years, decreased percent red color. Annual yield of all cultivars was significantly increased by N rate in a single year, but their cumulative yields were not different between treatments as a result of rate or timing. Altering the timing of N application within 12 wafb only affected leaf and fruit tissue N concentration. Leaf N was higher after 4 weeks of fertigation any time, although concentrations declined over the growing season, reaching minimum values around harvest. Fruit N was increased by fertigation 4 to 12 wafb. Yield, fruit firmness, and color were unaffected by fertigation timing. Critical fruit quality issues for ‘Gala’ and ‘Silken’ were small fruit size, for Ambrosia low fruit numbers, and for ‘Cameo’ soft fruit. ‘Fuji’, which achieved high yield and leaf N concentration and firm fruit, had poor red color regardless of N treatments.

We have previously shown that nucleosome loss, obtained by repressing histone H4 mRNA synthesis, activates otherwise inactive PHO5, GAL1, and CYC1 gene promoters (fused to the bacterial beta-galactosidase [lacZ] reporter gene) to moderate levels of activity (approximately 2 to 15% of fully induced levels). We now report that nucleosome loss activates the expression of two additional promoters that are normally induced by independent mechanisms: CUP1 (induced by heavy-metal toxicity) and HIS3 (induced by amino acid starvation). Surprisingly, the level of CUP1-lacZ and HIS3-lacZ activation by nucleosome loss approximates fully induced levels of transcription. These CUP1 and HIS3 promoter activities are increased similarly from either episomal or genomic constructs. Our results emphasize the universality of the mechanism by which nucleosome loss activates yeast promoters. Moreover, a comparison of absolute levels of activation for different promoters suggests that activation by nucleosome loss results in a relatively constant level of activation, while levels obtained by normal induction vary considerably. These data argue that nucleosome loss may play a uniquely dominant role in the regulation of certain promoters.

We have previously shown that nucleosome loss, obtained by repressing histone H4 mRNA synthesis, activates otherwise inactive PHO5, GAL1, and CYC1 gene promoters (fused to the bacterial beta-galactosidase [lacZ] reporter gene) to moderate levels of activity (approximately 2 to 15% of fully induced levels). We now report that nucleosome loss activates the expression of two additional promoters that are normally induced by independent mechanisms: CUP1 (induced by heavy-metal toxicity) and HIS3 (induced by amino acid starvation). Surprisingly, the level of CUP1-lacZ and HIS3-lacZ activation by nucleosome loss approximates fully induced levels of transcription. These CUP1 and HIS3 promoter activities are increased similarly from either episomal or genomic constructs. Our results emphasize the universality of the mechanism by which nucleosome loss activates yeast promoters. Moreover, a comparison of absolute levels of activation for different promoters suggests that activation by nucleosome loss results in a relatively constant level of activation, while levels obtained by normal induction vary considerably. These data argue that nucleosome loss may play a uniquely dominant role in the regulation of certain promoters.

<table width="645" border="1" cellspacing="0" cellpadding="0"><tbody><tr><td valign="top" width="408"><p> </p><p>Study on spatial distribution of metal Fe in the coastal area of Staring Bay, Southeast Sulawesi has been carried out. This study aims to determine the spatial distributions of heavy Fe in the coastal area of Staring Bay. Sampling was conducted at 12 stations along the bay through the purposive sampling method. Determination of heavy metal Fe concentration was performed utilizing the <em>Atomic Absorption Spectrophotomet</em><em>ry</em><em> </em>(AAS). Spatial analysis was performed with IDW interpolation method using a software ArcGIS 10.3. The results showed that the concentration of metal Fe at 12 stations was in the range of 0.00187 ppm to 0.01296 ppm whereby the highest level was found at station 7 (mouth of the Laonti river). The spatial analysis in 12 stations confirmed that in the coastal areas of Woru-woru village (near the mouth of the Laonti river) to Gala Island and Wandahea village up to Intan Island have been contaminated by metal Fe ranged from 0.0106-0.0117 ppm and 0.0118-0.013 ppm, respectively. The contamination factor of metal Fe was moderate. Based on the values of CF, the highest contamination of heavy metal Fe is at station 7.</p><p> </p><p>Keywords: Spatial analysis, Fe, IDW, CF, Staring Bay</p><p class="BodyAbstract"> </p><p class="BodyAbstract"> </p><p>Telah dilakukan studi distribusi spasial logam Fe di perairan Teluk Staring, Sulawesi Tenggara. Penelitian ini bertujuan untuk menentukan sebaran spasial logam Fe di perairan Teluk Staring. Pengambilan sampel dilakukan 12 stasiun di perairan teluk dengan metode <em>purposive sampling</em>. Penentuan kadar logam Fe pada sampel air laut menggunakan <em>Atomic Absorption Spectrophotomet</em><em>ry</em><em> </em>(AAS). Analisis spasial dilakukan dengan metode interpolasi IDW menggunakan <em>software</em> ArcGIS 10.3. Hasil penelitian menunjukkan bahwa kadar logam Fe di 12 stasiun penelitian berkisar antara 0,00187-0,01296 ppm dengan kadar tertinggi berada pada stasiun 7 (muara Sungai Laonti). Hasil analisis spasial pada 12 stasiun menunjukkan bahwa di daerah pesisir Desa Woru-woru (dekat muara Sungai Laonti) hingga Pulau Gala dan Desa Wandahea hingga Pulau Intan telah terkontaminasi logam Fe dengan kisaran 0,0106-0,0117 ppm dan 0,0118-0,013 ppm. Faktor kontaminasi logam Fe bersifat moderat. Berdasarkan nilai CF, kontaminasi tertinggi oleh logam Fe terdapat pada stasiun 7.</p><p> </p><p>Kata kunci:<em> </em>Analisis spasial, Fe, IDW, CF, Teluk Staring</p><p> </p></td></tr></tbody></table>

HES6 is a novel member of the family of basic helix–loop–helix mammalian homologues of Drosophila Hairy and Enhancer of split. We have analyzed the biochemical and functional roles of HES6 in myoblasts. HES6 interacted with the corepressor transducin-like Enhancer of split 1 in yeast and mammalian cells through its WRPW COOH-terminal motif. HES6 repressed transcription from an N box–containing template and also when tethered to DNA through the GAL4 DNA binding domain. On N box–containing promoters, HES6 cooperated with HES1 to achieve maximal repression. An HES6–VP16 activation domain fusion protein activated the N box–containing reporter, confirming that HES6 bound the N box in muscle cells. The expression of HES6 was induced when myoblasts fused to become differentiated myotubes. Constitutive expression of HES6 in myoblasts inhibited expression of MyoR, a repressor of myogenesis, and induced differentiation, as evidenced by fusion into myotubes and expression of the muscle marker myosin heavy chain. Reciprocally, blocking endogenous HES6 function by using a WRPW-deleted dominant negative HES6 mutant led to increased expression of MyoR and completely blocked the muscle development program. Our results show that HES6 is an important regulator of myogenesis and suggest that MyoR is a target for HES6-dependent transcriptional repression.

We report that Drosophila unconventional myosin VI, encoded by Myosin heavy chain at 95F (Mhc95F), is required for both imaginal disc and egg chamber morphogenesis. During oogenesis, Mhc95F is expressed in migrating follicle cells, including the border cells, which migrate between the nurse cells to lie at the anterior of the oocyte; the columnar cells that migrate over the oocyte; the centripetal cells that migrate between the oocyte and nurse cells; and the dorsal-anterior follicle cells, which migrate to secrete the chorionic appendages. Its function during development has been studied using a targeted gene silencing technique, combining the Gal4-UAS targeted expression system and the antisense RNA technique. Antibody staining shows that the expression of myosin 95F is greatly decreased in follicle cells when antisense Mhc95F RNA is expressed. Interfering with expression of Drosophila myosin VI at various developmental stages frequently results in lethality. During metamorphosis it results in adult flies with malformed legs and wings, indicating that myosin VI is essential for imaginal disc morphogenesis. During oogenesis, abnormal follicle cell shapes and aberrant follicle cell migrations are observed when antisense Mhc95F is expressed in follicle cells during stages 9 to 10, suggesting that the Drosophila myosin VI is required for follicle cell epithelial morphogenesis.

Abstract Over 40% of cases of multiple myeloma (MM) are associated with translocations of the immunoglobulin heavy (IgH) chain gene. The t(4;14) translocation, present in ca. 15% of myeloma cases, results in the overexpression of two potential oncogenes, MMSET and FGFR3, via juxtaposition of their endogenous promoters to regulatory elements of the IgH locus. The presence of t(4;14) and MMSET overexpression are adverse prognostic factors in MM irrespective of FGFR3 expression, implicating MMSET in disease pathogenesis. We previously reported the presence of repression domains and the ability of MMSET to methylate histones. Examination of a number of MMSET isoforms generated by different chromosomal breakpoints in the t(4;14) translocation indicated that a N-terminal portion of the protein containing a PWWP domain mediated tight association of MMSET with chromatin. To determine if this region of the protein could mediate DNA binding we incubated bacterially expressed MMSET with DNA cellulose. Both the N-terminal and C-terminal portions of the protein showed DNA binding activity with different affinities. To isolate DNA sequences potentially bound by MMSET we incubated immunoprecipitated MMSET with a library of human CpG island DNA fragments, selected the bound DNA and performed several rounds of re-amplification and binding of selected sequences. A small family of clones was obtained, having several sequence motifs in common, suggesting specific DNA binding activity by the MMSET complex. The C-terminal region of MMSET containing a SET domain and a PHD finger, in addition to binding naked DNA, bound to native histones H3 and H4. These data suggest that MMSET may specifically target particular genes through recognition of DNA sequences and histones, or possibly specific histone modifications. Subsequently, MMSET may regulate these genes by further modifying the adjacent chromatin. In vitro analysis showed that recombinant MMSET could methylate several lysine residues on core histones, including H3K4, H3K36 and H4K20. However, MMSET immunopurified from a t(4;14)-positive myeloma cell line was only able to methylate histone H4. Additionally, a B-cell line engineered to overexpress MMSET in a conditional manner showed a global increase in the level of tri-methylated H4K20 and modulation of specific sets of genes involved in apoptosis. To determine if MMSET could indeed affect the chromatin configuration of a model gene, MMSET was fused to the Gal4 DNA binding domain and expressed in cells harboring a chromatin-embedded Gal4 reporter. MMSET repressed this reporter and chromatin immunoprecipitation demonstrated that this was accompanied by an increase in H4K20 tri-methylation. Finally, we found that endogenous MMSET could complex with Lysine-Specific Demethylase 1 (LSD1). Accordingly, the targeting of MMSET to the Gal4 reporter gene also led to a loss of H3K4 methylation, consistent with transcriptional repression. Collectively these data indicate that MMSET is a transcriptional effector that can target specific segments of chromatin and mediate a series of repressive changes. Misexpression of MMSET may lead to significant genetic re-programming of the B cell and contribute to myeloma development.

The known global secular change in the distribu­tion of carbon isotopes between the Palaeozoic and Mesozoic is the basis of a new oil-source correlation tool. The carbon isotopic signatures of n-alkanes, in combination with information about the distribu­tions of diagnostic biomarkers have been used to classify Perth Basin oils according to the age of the source. These data confirm that most of the oil in the northern Perth Basin originates from the basal section of the Kockatea Shale.Oils exclusively from Triassic sources are isotopically light with n-alkane 813C values near −34%o PDB. Jurassic oil from Gage Roads-1 is isotopically heavy (~24%o) and is also distinctive in its relatively high content of conifer-derived aromatic hydrocar­bons. Condensates from Jurassic source intervals in the Dandaragan Trough are isotopically heteroge­neous with n-alkane 813C values between −25%o and −29%o. The Whicher Range-1 condensate, of appar­ent Permian origin, is isotopically heavy with n-alkane 5l3C values near −25%o. The isotopic data provide information about variation in sedimen­tary facies and possible multiple sources that is not evident from the biomarker signatures. All the Jurassic oils have significant amounts of bicadinanes, resin-derived biomarkers until recently attributed exclusively to tropical angiosperms.A strong excursion in the isotopic signature of organic carbon is present in core at 2,293 m in the Woodada-2 borehole and occurs with no obvious lithological change. Similar isotope shifts are known to mark the Permian-Triassic boundary globally and have been previously recognised in the Bonaparte, Bowen, Canning, Carnarvon and tenta­tively in the southern Perth basins. The excursion in Woodada-2 is abrupt and suggests a significant time break in sedimentation. However, diagnostic Permian palynoflora or fauna have not been de­tected below 2,293 m in the Woodada-2 core, and hence, the assignment of a Permian-Triassic con­tact cannot be made unequivocally with the exist­ing data.

Abstract. The performance of distributed hydrological models depends on the resolution, both spatial and temporal, of the rainfall surface data introduced. The estimation of quantitative precipitation from meteorological radar or satellite can improve hydrological model results, thanks to an indirect estimation at higher spatial and temporal resolution. In this work, composed radar data from a network of three C-band radars, with 6-minutal temporal and 2 × 2 km2 spatial resolution, provided by the Catalan Meteorological Service, is used to feed the RIBS distributed hydrological model. A Window Probability Matching Method (gage-adjustment method) is applied to four cases of heavy rainfall to improve the observed rainfall sub-estimation in both convective and stratiform Z/R relations used over Catalonia. Once the rainfall field has been adequately obtained, an advection correction, based on cross-correlation between two consecutive images, was introduced to get several time resolutions from 1 min to 30 min. Each different resolution is treated as an independent event, resulting in a probable range of input rainfall data. This ensemble of rainfall data is used, together with other sources of uncertainty, such as the initial basin state or the accuracy of discharge measurements, to calibrate the RIBS model using probabilistic methodology. A sensitivity analysis of time resolutions was implemented by comparing the various results with real values from stream-flow measurement stations.

Abstract Abstract 5143 Cerebral sinovenous thrombosis (CSVT) is a rare condition with a wide spectrum of non-specific symptoms, which makes it occasionally difficult to diagnose. CSVT has been associated with various etiologies including dehydration, hypercoagulable states, neoplasmic invasion of a venous sinus, intracranial and systemic infections, use of oral contraceptives, puerperium and pregnancy. Although iron deficiency anemia (IDA) has been reported as a cause of CSVT in several pediatric cases, this association is extremely rare. To our knowledge, IDA-associated CSVT in teenagers has been rarely reported. Here, we present the case of a 13-year old female with complete thrombosis of the vein of Galen, the straight sinus, and the left internal cerebral vein related to iron deficiency anemia as a result of severe menorrhagia. She initially presented with three-week history of headaches, nausea and vomiting. She was initially diagnosed and treated for bacterial sinusitis by her primary pediatrician, without symptom relief. She then suffered a syncopal episode, reason why she was evaluated at our institution. Initial laboratories revealed a slightly increased PT (15. 6 secs), hemoglobin of 5. 1 g/dL, MCV 63. 6 and D-dimer 1. 31. Non-contrast brain CT demonstrated no evidence of stroke, hemorrhage or mass. However, an abnormal hyperdensity in the straight sinus, inferior sagittal sinus, vein of Galen, and deep cerebral veins, were suggestive of venous thrombosis. Findings were then confirmed by brain MRI/MRV/MRA and CT angiogram. A bleeding work-up performed based on her history of heavy menses was normal. Her ferritin level was significantly decreased (6 ng/mL). Iron supplementation was initiated as well as progestin-only hormonal therapy for menstrual cycle regulation. The patient's clinical status improved back to baseline during her 8-day admission. She was discharged home on anticoagulation with scheduled follow up. Brain MRI/MRV six months later showed patency of the cerebral veins and dural venous sinuses. IDA should be considered as an underlying cause of CSVT in pediatric patients, particularly in patients with other risk factors for thrombosis including dehydration, regardless of their age. Early recognition and management of CSVT is critical to minimize the possibility of permanent neurologic damage. Physicians should be aware of the non-specific signs and symptoms of CSVT and should have a high index of suspicion in patients with anemia. Disclosures: No relevant conflicts of interest to declare.

The article is aimed at indicating and analyzing connections existing between De re coquinaria and medicine. It is mostly based on the resources of extant Greek medical treatises written up to the 7th century A.D. As such it refers to the heritage of the Corpus Hippocraticum, Dioscurides, Galen, Oribasius, Anthimus, Aetius of Amida, Paul of Aegina, to name but the most important. The authors of the study have tried to single out from De re coquinaria those recipes which have the tightest connections with medicine. They are: a digestive called oxyporum, two varieties of dressings based on fish sauce, i.e. oxygarum digestibile and oenogarum, herbal salts (sales conditi), spiced wine (conditum paradoxum), honeyed wine (conditum melizomum viatorum), absinthe (absintium Romanum), rosehip wine (rosatum), a soup (or relish) pulmentarium, a pearl barley-based soup termed tisana vel sucus or tisana barrica, an finally nettles. In order to draw their conclusions, the authors of the article projected the data from De re coquinaria upon a wide background of extant information retrieved from medical writings. The conclusions demonstrate that those who contributed to the present form of De re coquinaria, even if they did not possess strictly medical expertise, remained under a heavy influence of Hippocratic and Galenic teachings. As a result, De re coquinaria should be seen as yet another work of antiquity that supports the existence of an indissoluble bond between medical doctrines and culinary practice of the times.

The objectives of this experiment were to test the efficacy of a mechanical string thinner (Darwin PT-250; Fruit-Tec, Deggenhauserertal, Germany) on apple and to identify an optimal range of thinning severity as influenced by spindle rotation speed. Trials were conducted in 2010 and 2011 at the Pennsylvania State University Fruit Research and Extension Center in Biglerville, PA, on five-year-old ‘Buckeye Gala’/M.9 apple trees that were trained to tall spindle. A preliminary trail on five-year-old ‘Cripps Pink’/M.9 was conducted to determine the relationship between string number and thinning severity. As the number of strings increased, the level of thinning severity increased. A range of spindle speeds (0 to 300 rpm) was applied to the same trees for two consecutive years. As spindle speed increased, blossom density (blossom clusters per limb cross-sectional area) was reduced as was the number of blossoms per spur. In 2010, leaf area per spur was reduced 9% to 45%. In 2011, the fastest spindle speed reduced leaf area per spur 20%. Although increased spindle speed reduced cropload, injury to spur leaves may have inhibited increases in fruit size. The largest gain in fruit weight was 28 g (300 rpm) compared with the control. In both years, the most severe thinning treatments reduced yield by more than 50%. There was no relationship between spindle speed and return bloom. Severe thinning treatments (240 to 300 rpm) caused significant reductions in spur leaf area, yield, and fruit calcium and did not improve fruit size or return bloom. Spindle speeds of 180 and 210 rpm provided the best overall thinning response and minimized injury to spur leaves, but cropload reduction was insufficient in years of heavy fruit set. Therefore, mechanical blossom thinning treatments should be supplemented with other thinning methods. Mechanical string thinning may be a viable treatment in organic apple production, where use of chemical thinners is limited.

Soil moisture is a critical parameter in numerical weather prediction (NWP) models because it plays a fundamental role in the exchange of water and energy cycles between the atmosphere and the land surface through evaporation. To improve the forecast skills of the Weather Research and Forecasting (WRF) model in Xinjiang, China, this study investigated the impacts of soil moisture initialization on the WRF forecasts by performing a series of simulations. A group of simulations was conducted using the single-column model (SCM) from 1200 UTC on 15 to 18 August 2019, at Urumchi, Xinjiang (43.78° N, 87.6° E); another was performed using the WRF model for a real weather case in Xinjiang from 0000 UTC 15 August to 1200 UTC 18 August 2019, which included an episode of heavy precipitation and gales. Our most notable findings are as follows. Specific humidity increases and potential temperature decreases persistently when soil moisture increases because of soil water evaporation. Soil moisture initialization could impact the energy budget and modulate the partition of the total available energy at the land surface significantly through evaporation and the greenhouse effect. Replacing the soil moisture with a proper multiple of the National Centers for Environmental Prediction (NCEP) Global Forecast System (GFS) soil moisture data could significantly improve the critical success index (CSI) and frequency bias (FBIAS) of precipitation and the root-mean-squared errors (RMSEs) of 2-m specific humidity and 2-m temperature. These findings indicate the prospect of a new way to improve the forecast skills of WRF in Xinjiang or other similar regions.

Metallurgy and heavy engineering construction, which are considered the most energy-intensive industries, place great focus on complex shaped thick-gage plate metal items of equipment with wall thickness exceeding 40 mm and diameter/width of up to 4000 mm. Such items of equipment include large machine parts manufactured by means of hot plate stamping, such as bodies of rotation (for example, the segment of the radial surface of converter shell, the bottom part of degassing unit, etc.) utilized as pressure-operated devices, vessels, tanks and other facilities by metallurgical, petrochemical, oil and gas, and nuclear industries. Presently known manufacturing methods of such items of equipment, for instance, stamping methods, have a number of technological problems. In the present paper, creation and development of the theory and technology of manufacturing different large bodies based on the combination of plate rolling and stamping processes, as well as the combination of asymmetric rolling and plastic bending processes, are proposed. The goal was to develop a cost-effective technology of producing large-size bodies of rotation in the conditions of a thick-plate mill. The rolling of the package forms the basis of the first stage of the new process. The package consists of the upper (punch) base, the lower (matrix) base, and the blank plate situated between them. The economic benefit from installing the developed technology based only on the combination of asymmetric rolling and plastic bending processes was more than 1 million dollars. Casings on two converters were produced and installed in the oxygen-converter plant.

A study was conducted to examine the inheritance of partial resistance to apple scab [Venturia inaequalis (Cke.) Wint.] using as parents a set of apple (Malus × domestica Borkh.) cultivars that show a range of field resistance to the disease, but are not known to carry any major-gene resistance. Akane, Alkmene, Antonovka, Carola, Chehalis, Goldgelbe, Katja and Summerred were used as pollen parents, and Spartan and an unnamed selection of Splendour × Gala parentage were used as seed parents in a factorial 2 × 8 mating design. One hundred seedlings of each family were planted in a randomized complete block design at a site with heavy annual natural scab infections. Each seedling was rated for infection severity for 3 consecutive years using a six-point categorical scale. A χ2 procedure was used to estimate the contribution of each parent to field resistance (analogous to general combining ability, GCA) and the contribution of the particular male-female combination (analogous to specific combining ability, SCA). Infection severity tended to increase over the 3 yr of the study. Antonovka and Chehalis had the highest analogous GCA for resistance (defined here as absence of sporulating lesions). Specific combining ability was present in 2 of 3 yr, but was small in magnitude relative to GCA. The field resistance of a given parent tended to be a poor predictor of its breeding value. However, 13 of the 16 families had at least 30% of seedlings with a potentially useful degree of partial resistance (low severity of infection). The results are discussed in the context of breeding apples with durable scab resistance.Key words: Fruit breeding, Malus, partial resistance, Venturia inaequalis

For a defence of ‘crudum’ against Courtney's strictures, see the reviews by Goodyear and Reeve. I am presently concerned not with the unresolved crux in verse 144, but with the medical reason for the death of the glutton. Galen (xix. 692–3 K), quoted by Mayor, warned that one should not bathe after eating ἵνα μ μϕραξις κατ νεϕρὺς κα ἦπαρ γνηται. More recently, Courtney ad loc. has quoted Persius 3.98ff. and has attributed the death to ‘apoplexy’, which in more modern parlance is called a ‘stroke’ or a ‘cerebral haemorrhage’. What Persius and Juvenal are actually describing is not a stroke but what was formerly known as ‘acute indigestion’ and is now called a ‘heart attack’, as indeed ought to have been obvious from ‘nescio quid trepidat mihi pectus’ at Persius 3.88, and ‘tange, miser, uenas et pone in pectore dextram’ at 3.107. As Duff says, ‘the natural and ordinary time for bathing was just before the cena, but the gluttons of this time had discovered that digestion was temporarily promoted by the unhealthy practice of bathing in very hot water immediately after the meal’. Modern medical research has shown why this practice was very unhealthy indeed. As a meal is digested, the pulse rate is elevated, and bathing in hot water increases it even further. The consumption of alcohol, such as that described at Persius 3.92–3 and 99–100, would further accelerate the heart beat. The synergistic effect of these three circumstances, digesting a heavy meal, metabolising a large dose of alcohol, and bathing in hot water, was liable to cause a heart attack in an overweight man whose arteries were clogged with cholesterol.

Compact object mergers eject neutron-rich matter in a number of ways: by the dynamical ejection mediated by gravitational torques, as neutrino-driven winds, and probably also a good fraction of the resulting accretion disc finally becomes unbound by a combination of viscous and nuclear processes. If compact binary mergers indeed produce gamma-ray bursts, there should also be an interaction region where an ultra-relativistic outflow interacts with the neutrino-driven wind and produces moderately relativistic ejecta. Each type of ejecta has different physical properties, and therefore plays a different role for nucleosynthesis and for the electromagnetic (EM) transients that go along with compact object encounters. Here, we focus on the dynamic ejecta and present results for over 30 hydrodynamical simulations of both gravitational wave-driven mergers and parabolic encounters as they may occur in globular clusters. We find that mergers eject approximately 1 per cent of a Solar mass of extremely neutron-rich material. The exact amount, as well as the ejection velocity, depends on the involved masses with asymmetric systems ejecting more material at higher velocities. This material undergoes a robust r-process and both ejecta amount and abundance pattern are consistent with neutron star mergers being a major source of the ‘heavy’ ( A >130) r-process isotopes. Parabolic collisions, especially those between neutron stars and black holes, eject substantially larger amounts of mass, and therefore cannot occur frequently without overproducing gala- ctic r-process matter. We also discuss the EM transients that are powered by radioactive decays within the ejecta (‘macronovae’), and the radio flares that emerge when the ejecta dissipate their large kinetic energies in the ambient medium.

One-year-old `Gala'/M7 apple trees were potted into 30-L containers and approach-grafted about 45 cm above the graft union in late Spring 2003. Trees were grown with both tops for the remainder of the 2003 season in a greenhouse. In Apr. 2004, one of the tops was removed. Trees were fully watered by an overhead irrigation system until July 2004, when trees were subjected to one of four irrigation regimes: control received >100% of ETc applied evenly to the two pots; PRD100 received >100% ETc applied to one pot only; and two regimes received 50% ETc applied to either one (PRD50) or both pots (DI50). Both gravimetric (tripod) and volumetric (time-domain reflectometry) soil moisture measurements were taken daily prior to and after irrigations. In addition, heavy isotope H2O (18O) was applied to one of the two root compartments and analyzed in the leaves to further determine the validity of the model. Sap flow was monitored in six split-rooted trees using miniaturized heat-pulse probes inserted into the stem above the graft union and into each of the two root systems below the graft union. Under fully irrigated conditions, root sap flow was proportional to root trunk cross-sectional area, and was not a function of root system origin (i.e., roots of mother plant with original top remaining or roots of daughter plant with original top detached). Water uptake from a previously dried root zone was rapid when the irrigated side was switched, but much more gradual when the other side was maintained wet. Interactions between soil moisture and sap flow in relation to factors governing canopy demand will be presented.

Sunkoshi Small Hydropower Plant (SSHP) is a run-of-river type project constructed in Sunkoshi River located in Sindhupalchowk District of Bagmati zone of Central Development Region, Nepal. The plant started its commercial operation since March 2005. During the year 2014, 2015 and 2016 the plant faced series of natural disaster events; landslide at Jure village on 2 August 2014, earthquake (7.8 magnitude) on 25 April 2015, landslide dammed flood in Sunkoshi River on 11 August 2015 and Glacier Lake Outburst Flood (GLOF) in Sunkoshi River on 5 July 2016. The Jure landslide created 55 m dam across Sunkoshi River. Thus created landslide dammed lake inundated the powerhouse of SSHP for 36 days. About seven million cubic meters of water was reserved in the lake. The event damaged entire powerhouse building, Electromechanical Equipment (EM), tailrace culvert, portion of steel penstock pipe and staff quarter. The rehabilitation works after Jure landslides included strengthening of powerhouse building and tailrace culvert, winding of generators, replacement of electromechanical equipment and portion of penstock pipe and change of transmission line alignment. On 25 April 2015, most of the rehabilitation works were completed. The EM experts were conducting a wet test for power generation when the power-plant was hit by other natural disaster - earthquake of 7.8 Rector Scale. The earthquake and its aftershocks followed by landslide dammed outburst flood of 11 August 2015 damaged headworks structures - formed a cavern of 56.6 m3 below gravel trap, collapsed entire powerhouse building and damaged newly installed electromechanical equipment, created several landslides along water way alignment and damaged about 900 m of penstock alignment. Some innovations in designs were introduced such as construction of sliding type saddle supports, bio-engineering combined with civil engineering structures to stabilize landslides, retrofitting of powerhouse building, use of crackamite and rock drill and avoidance of heavy masonry wall and gable wall in powerhouse. After rehabilitation works, the power plant re-operated since 4 January 2016 - after about 18 months. However, the plant was again affected by a Glacier Lake Outburst Flood (GLOF) in Botekoshi River on 5 July 2016.

Abstract Over 40% of cases of multiple myeloma (MM) are associated with translocations of the immunoglobulin heavy (IgH) chain gene gene. The t(4;14) translocation, present in ca. 20% of myeloma cases, results in the overexpression of two potential oncogenes, MMSET and FGFR3, via juxtaposition of their endogenous promoters to regulatory elements of the IgH locus. The presence of t(4;14), and MMSET overexpression, is an adverse prognostic factor in MM irrespective of FGFR3 expression. MMSET contains several conserved motifs found in proteins involved in chromatin function (PWWP, HMG, PHD domains) and in the epigenetic control of transcription (SET domain). Accordingly, we found that the two main isoforms of the MMSET protein exhibit exclusive nuclear localization in both transfected fibroblasts and myeloma cells carrying t(4;14). Towards our goal of defining the ability of MMSET to affect gene regulation and contribute to the disease pathogenesis, we found that the SET domain of MMSET possesses in vitro methyltransferase activity specific for core histones H3 and H4. Using a computational approach and theoretical extrapolation from the solved NMR structure of vSET, we identified residues in the active site of MMSET essential for catalysis, whose mutation drastically reduces enzymatic activity. Reporter assays using Gal4 fusion constructs showed that both the amino terminus of MMSET, containing the PWWP and HMG domains, as well as the SET-containing carboxy terminus act as transcriptional repressors. MMSET interacts physically and functionally with a number of known co-repressor molecules, such as HDAC1, HDAC2, Sin3a, and SIRT1, but not HDAC4 or HDAC6. As such, MMSET co-expression enhances HDAC1 and HDAC2-mediated repression in transcriptional reporter assays, and MMSET repression is partially relieved by the addition of an HDAC inhibitor. A yeast two hybrid screen identified a number of other functional partners of MMSET, including ZNF331/RITA (Rearranged in Thyroid Adenoma), a KRAB domain/zinc finger protein previously implicated in malignancy. MMSET and ZNF331 co-localize in the nuclei of transfected fibroblasts, co-immunoprecipitate, and display cooperative repression in reporter assays. Collectively, these data support the idea that MMSET is a biologically active, bifunctional transcriptional mediator acting as a HMT enzyme in chromatin remodeling and as a complex adaptor in the recruitment of repressor species. Presently we are modeling the biological effects of MMSET through a conditional overexpression system in a B cell line. While low levels of MMSET are ubiquitiously expressed, induction of high levels of MMSET expression in the B cell line is associated with growth suppression and G1 arrest. While paradoxical for a presumed oncoprotein, such actions have been observed for other disease-associated proteins such as Runx1/MTG8. In contrast, a myeloma cell line harboring t(4;14) proliferates in the presence of high level MMSET expression. RNAi-mediated knockdown of MMSET in these cells induces apoptotic cell death. This suggests that MMSET may be critical for growth and survival of myeloma cells. Profiling of gene expression changes in these systems should link the transcriptional and biological activities of MMSET.

Core Binding Factor (CBF) is a family of heterodimeric transcription factors consisting of a CBFα subunit (AML1/RUNX1, AML2, or AML3) and CBFβ. The CBFα subunits bind DNA and regulate transcription. CBFβ increases the DNA affinity of the CBFα subunits. CBF induces lineage-specific genes and also accelerates the cell cycle via gene activation. CBFβ-SMMHC, encoded by the inv(16) or t(16;16) chromosomes in 8% of acute myeloid leukemia (AML) cases, is a fusion protein containing amino acids 1–165 of the 182 residue CBFβ and the α-helical rod domain of smooth muscle myosin heavy chain (SMMHC). The SMMHC domain mediates multimerization dependent upon a 28 residue, C-terminal Assembly Competence Domain (ACD). CBFβ-SMMHC potentially inhibits CBF by sequestering CBFα subunits in multimeric complexes in the nucleus. The CBFβ domain of CBFβ-SMMHC retains the ability to interact with AML1, and the resulting heterodimer can bind DNA. In addition, the SMMHC domain interacts directly with corepressors, including mSin3A, allowing AML1:CBFβ-SMMHC to directly repress CBF-regulated genes. Repression is obviated, however, upon deletion of the ACD. We have now carried out a mutagenic analysis of the ACD, in an effort to separate its contributions to multimerization and repression. We designated the 4 α-helices of the ACD as A, B, C, and D, and the subseqent helix as E. Each helix consists of 7 residues, abcdefg, with a and d hydrophobic and mediating dimerization, e and g often forming salt-bridges to stabilize this dimer, and b, c, and f available to mediate multimerization and corepressor binding. We mutated the bcf residues as a cluster within helix A, B, C, D, or E and also generated additional combinations: BC, CD, DE, BCD, ABCD, and ABCDE, the latter carrying alterations in 15 residues on the outer surface of the dimeric coiled-coil. Mutants DE, BCD, ABCD, and ABCDE were defective for multimerization, inhibition of CBF DNA-binding, nuclear localization, and inhibition of Ba/F3 proliferation. Even when directed to the nucleus using a nuclear localization signal, DE and ABCD did not inhibit CBF DNA-binding or CBF-mediated cell cycle progression. In addition, mutants B, C, or D did not inhibit Ba/F3 proliferation, and mutants A or E only mildly reduced proliferation. As each of these single helix mutants assembled into multimers, multimerization and sequestration of CBFα subunits is not sufficient for CBF inhibition. Mutation of helix C or E also prevented transrepression by a Gal4 DNA-binding domain-SMMHC fusion protein, in NIH 3T3 cells (other mutants remain to be evaluated in this assay). Of note, mutants C and E effectively coimmunoprecipitated with mSin3A from Ba/F3 extracts, suggesting that additional corepressors participate in suppression of CBF activities in these cells. In summary, we have identified CBFβ-SMMHC variants which multimerize and are defective for repression of CBF-regulated genes, but we have yet to identify mutants which cannot multimerize but still inhibit CBF. This may reflect overlap of the corepressor-binding site with residues required for multimerization. Nevertheless, we have identified amino acids on the outer surface of the ACD critical for inhibition of CBF. Drugs targeting the BCD or DE cluster of bcf residues may simultaneously prevent CBFβ-SMMHC multimerization and corepressor interaction and assist in the therapy of AMLs expressing this oncoprotein.

There are different apprehensions regarding the contemporary assessment system. Often, I listen to my colleagues saying that multiple-choice questions are seen as easier to score. Why can’t all assessments be multiple-choice tests? Some others would say, whether the tests given reflect what students will need to know as competent professionals? What evidence can be collected to make sure that test content is relevant? Others come up with concerns that there is a perception amongst students that some examiners are harsher than others and some tasks are easier than others. What can be done to evaluate whether this is the case? Sometimes, the students come up with queries that they are concerned about being observed when interacting with patients. They are not sure why this is needed. What rationale is there for using workplace-based assessment? Some of the students worry if the pass marks for the assessments are ‘correct’, and what is the evidence for the cut-off scores? All these questions are important, and I would deliberate upon them with evidence from the literature. Deliberating on the first query of using multiple-choice questions for everything, we know that assessment of a medical student is a complex process as there are multiple domains of learning such as cognition, skills, and behaviors (Norcini and McKinley, 2007)(Boulet and Raymond, 2018). Each of the domains further has multiple levels from simple to complex tasks (Norcini and McKinley, 2007). For example, the cognition is further divided into six levels, starting from recall (Cognition level 1 or C1) up to creativity (Cognition level 6 or C6) (Norcini and McKinley, 2007). Similarly, the skills and behaviors also have levels starting from observation up to performance and practice (Norcini and McKinley, 2007). Moreover, there are different competencies within each domain that further complicates our task as an assessor to appropriately assess a student (Boulet and Raymond, 2018). For instance, within the cognitive domain, it is not just making the learning objectives based on Bloom’s Taxonomy that would simplify our task because the literature suggests that individuals have different thinking mechanisms, such as fast and slow thinking to perform a task (Kahneman, 2011). We as educationalists do not know what sort of cognitive mechanism have we triggered through our exam items (Swanson and Case, 1998). Multiple Choice Questions is one of the assessment instruments to measure competencies related to the cognitive domain. This means that we cannot use multiple-choice questions to measure the skills and behaviors domains, so clearly multiple-choice questions cannot assess all domains of learning (Vleuten et al, 2010). Within the cognitive domain, there are multiple levels and different ways of thinking mechanisms (Kahneman, 2011). Each assessment instrument has its strength and limitations. Multiple-choice questions may be able to assess a few of the competencies, also with some added benefits in terms of marking but there always are limitations. The multiple-choice question is no different when it comes to the strengths and limitations profile of an assessment instrument (Swanson and Case, 1998). There are certain competencies that can be easily assessed using multiple-choice questions (Swanson and Case, 1998). For example, content that requires recall, application, and analysis can be assessed with the help of multiple-choice questions. However, creativity or synthesis which is cognition level six (C6) as per Blooms’ Taxonomy, cannot be assessed with closed-ended questions such as a multiple-choice question. This means that we need some additional assessment instruments to measure the higher levels of cognition within the cognitive domain. For example, asking students to explore an open-ended question as a research project can assess the higher levels of cognition because the students would be gathering information from different sources of literature, and then synthesizing it to answer the question. It is reported that marking and reading the essay questions would be time-consuming for the teachers (McLean and Gale, 2018). Hence, the teacher to student’s ratio in assessing the higher levels of cognition needs to be monitored so that teachers or assessors can give appropriate time to assess the higher levels of cognition of their students. Hence, we have to use other forms of assessment instruments along with multiple-choice questions to assess the cognitive domain. This will help to assess the different levels of cognition and will also incite the different thinking mechanisms. Regarding the concerns, whether the tests given reflect what students will need to know as competent professionals? What evidence can be collected to make sure that test content is relevant? It is one of an important issue for medical education and assessment directors whether the tests that they are taking are reflective of the students being competent practitioners? It is also quite challenging as some of the competencies such as professionalism or professional identity formation are difficult to be measured quantitatively with the traditional assessment instruments (Cruess, Cruess, & Steinert, 2016). Moreover, there is also a question if all the competencies that are required for a medical graduate can be assessed with the assessment instruments presently available? Hence, we as educationalists have to provide evidence for the assessment of required competencies and relevant content. One of the ways that we can opt is to carefully align the required content with their relevant assessment instruments. This can be done with the help of assessment blueprints, or also known as the table of specifications in some of the literature (Norcini and McKinley, 2013). An assessment blueprint enables us to demonstrate our planned curriculum, that is, what are our planned objectives, and how are we going to teach and assess them (Boulet and Raymond, 2018). We can also use the validity construct in addition to the assessment blueprints to provide evidence for testing the relevant content. Validity means that the test is able to measure what it is supposed to measure (Boulet and Raymond, 2018). There are different types of validity but one of the validity that is required in this situation to establish the appropriateness of the content is the Content Validity. Content validity is established by a number of subject experts who comment on the appropriateness and relevance of the content (Lawshe, 1975). The third method by which the relevance of content can be established is through standard-setting. A standard is a single cut-off score to qualitatively declare a student competent or incompetent based on the judgment of subject experts (Norcini and McKinley, 2013). There are different ways of standard-setting for example Angoff, Ebel, Borderline method, etc. (Norcini and McKinley, 2013). Although the main purpose is the establishment and decides the cut-off score during the process, the experts also debate on the appropriateness and relevance of the content. This means that the standard-setting methods also have validity procedures that are in-built in their process of establishing the cut-off score. These are some of the methods by which we can provide evidence of the relevance of the content that is required to produce a competent practitioner. The next issue is the perception amongst students that some examiners are harsher than others and some tasks are easier than others. Both these observations have quite a lot of truth in them and can be evaluated following the contemporary medical education evaluation techniques. The first issue reported is that some examiners are harsher than others. In terms of assessment, it has been reported in the literature as ‘hawk dove effect’ (McManus et al, 2006, Murphy et al, 2009). There are different reasons identified in the literature for some of the examiners to be more stringent than others such as age, ethnic background, behavioral reasons, educational background, and experience in a number of years (McManus et al, 2006). Specifically, those examiners who are from ethnic minorities and have more experience show more stringency (McManus et al, 2006). Interestingly, it has been reported elsewhere how the glucose levels affect the decision making of the pass-fail judgments (Kahneman, 2011). There are psychometric methods reported in the literature, such as Rasch modeling that can help determine the ‘hawk dove effect’ of different examiners, and whether it is too extreme or within a zone of normal deviation (McManus et al, 2006, Murphy, et al, 2009). Moreover, the literature also suggests ways to minimize the hawk-dove effect by identifying and paring such examiners so the strictness of one can be compensated by the leniency of the other examiner (McManus et al, 2006). The other issue in this situation is that the students find some tasks easier than others. This is dependent on the complexity of tasks and also on the competence level of students. For example, a medical student may achieve independent measuring of blood pressure in his/her first year but even a consultant surgeon may not be able to perform complex surgery such as a Whipple procedure. This means that while developing tasks we as educationalists have to consider both the competence level of our students and the complexity of the tasks. One way to theoretically understand it is by taking help from the cognitive load theory (Merrienboer 2013). The cognitive load theory suggests that there are three types of cognitive loads; namely, the Intrinsic, Extraneous, and Germane loads (Merrienboer 2013). The intrinsic load is associated with the complexity of the task. The extraneous load is added to the working memory of students due to a teacher who does not plan his/her teaching session as per students' needs (Merrienboer 2013). The third load is the germane or the good load that helps the student to understand the task and is added by using teaching methods that helps students understand the task (Merrienboer 2013). The teachers can use different instructional designs such as the 4CID model to plan their teaching session of the complex tasks (Merrienboer 2013). One of the ways to understand the difficulty of the task can be to pilot test the task with few students or junior colleagues. Another way to determine the complexity of the task can be through standard-setting methods where a cut-off score is established after the experts discuss each task and determine its cut-off score based on their judgments (Norcini and McKinley, 2013). However, it is important that the experts who have been called for setting standards have relevant experience so as to make credible judgments (Norcini and McKinley, 2013). A third way to evaluate the complexity of tasks is by applying the post-exam item analysis techniques. The difficulty of the task is evaluated after the performance of students in the exam. Each item’s difficulty in the exam can be measured. The items can be placed from extremely easy (100% students correctly answered the item) to extremely difficult (100% students failed on that specific item). The item analysis enables the teachers to determine which tasks were easier in exams as compared to more difficult tasks. Another concern that comes from students is about their observation when interacting with patients. Health professions training programs require the interaction of students with patients. The student-patient interaction is not very often in initial years of student’s training due to the issues of patient safety, and due to the heavy workload on clinical faculty. However, with the passage of time in the training program, these student patient interactions increase. There is also a strong theoretical basis for better learning when the students are put in a context or a given situation (Wenger, 1998). For example, infection control can be taught through a lecture however the learning can be more effective if the students practically learn it in an operation theatre. Moreover, the undergraduate students or foundation year house job doctors are yet not competent enough to practice independently and require supervision for the obvious reasons of patient safety. Although, some of the students may not like being observed it is one of the requirements for their training. The examiners observing them can give them constructive feedback to further improve their performance (Etheridge and Boursicot, 2013). Feedback is one of the essential components of workplace-based assessments, and it is suggested in the literature that the time for feedback to the student should be almost equal to one-third of the procedure or task time (Etheridge and Boursicot, 2013), that is, for a fifteen minutes tasks, there should be at least five minutes for the feedback hence having a total of twenty minutes time on the whole. Further, it is important for the examiners and senior colleagues to establish trust in the competence of their students or trainees. The ‘trust’ is one of the behavioral constructs that also starts initially with an observation (Etheridge and Boursicot, 2013). Hence, observation of students or house officers by senior colleagues or teachers during clinical encounters is important to establish trust in student’s competence levels. Additionally, in the workplace, there are different skills that are required by the students to demonstrate, and each skill is quite different to others. There are different workplace-based assessment instruments and each of them assesses only certain aspects of student’s performance during clinical practice. For instance, the Mini Clinical Evaluation Exercise (Mini-CEX) can primarily assess the history taking and physical examination skills of students (Etheridge and Boursicot, 2013). Similarly, the Directly Observed Procedural Skills (DOPS) is required to assess the technical and procedural skills of students (Etheridge and Boursicot, 2013). More so, the Case-based Discussion (CBD) is required to assess clinical reasoning skills, decision-making skills, ethics, and professionalism (Etheridge and Boursicot, 2013). Further, multi-source feedback (MSF) or 360-degree assessment collects feedback about a student on their performance from multiple sources such as patients, senior and junior colleagues, nursing staff, and administrative staff (Etheridge and Boursicot, 2013). All these workplace-based assessments require observation of students so they can be given appropriate feedback on their technical and nontechnical skills (Etheridge and Boursicot, 2013). Hence, clinical encounters at the workplace are quite complex and require training of students from different aspects to fully train them that cannot be accomplished without observation. Some students also worry whether the pass marks for the assessments are ‘correct’, and what is the evidence for the cut-off score in their exams? A standard is a single cut-off score that determines the competence of a student in a particular exam (Norcini and McKinley, 2013). The cut-off score is decided by experts who make a qualitative judgment (Norcini and McKinley, 2013). The purpose is not to establish an absolute truth but to demonstrate the creditability of pass-fail decisions in an exam (Norcini and McKinley, 2013). There are certain variables related to standard setters that may affect the creditability of the standard-setting process; such as age, gender, ethnicity, their understanding of the learners, their educational qualification, and their place of work. Moreover, the definition of competence varies with time, place and person (Norcini and McKinley, 2013). Hence, it is important that the standard setters must know the learners and the competence level expected from them and the standard setters must be called from different places. This is one of the first requirements to have the profile of the standard setters to establish their credibility. Moreover, the selection of the method of standard setting is important, and how familiar are the standard setters with the method of standard-setting. There are many standard-setting methods for different assessment instruments and types of exams (Norcini and McKinley, 2013). It is essential to use the appropriate standard-setting method, and also to train the standard setters on that method of standard setting so they know the procedure. The training can be done by providing them certain data to solve it following the steps of the standard-setting procedure. The record of these exercises is important and can be required at later stages to show the experience of the standard setters. Further, every standard-setter writes a cut-off score for each item (Norcini and McKinley, 2013). The mean score of all the standard setters is calculated to determine the cut-off score for each item (Norcini and McKinley, 2013). The total cut-off score is calculated by adding the pass marks of each individual item (Norcini and McKinley, 2013). The cut-off scores for items would also help in differentiating the hawks from doves, that is, those examiners who are quite strict from those who are lenient (McManus et al, 2006). Hence, it is important to keep the record of these cut-off scores of each item for future records and to have a balanced standard-setting team for future exams (Norcini and McKinley, 2013). Additionally, the meeting minutes is an important document to keep the record for the decisions made during the meeting. Lastly, the exam results and post-exam item analysis is an important document to see the performance of students on each item and to make comparisons with the standard-setting meeting (Norcini and McKinley, 2013). It would be important to document the items that behaved as predicted by the standard setters and those items that would show unexpected responses; for example, the majority of the borderline students either secured quite high marks than the cut-off score or vice versa (Norcini and McKinley, 2013). All the documents mentioned above would ensure the creditability of the standard-setting process and would also improve the quality of exam items. There are many other aspects that could not be discussed in this debate on the contemporary assessment system in medical education. Another area that needs deliberations is the futuristic assessment system and how it would address the limitations of the current system? Disclaimer: This work is derived from one of the assignments of the author submitted for his certificate from Keele University. -------------------------------------------------------------------------- References Boulet, J. and Raymond, M. (2018) ‘Blueprinting: Planning your tests. FAIMER-Keele Master’s in Health Professions Education: Accreditation and Assessment. Module 1, Unit 2.’, FAIMER Centre for Distance Learning, CenMEDIC. 6th edn. London, pp. 7–90. Cruess, R. L., Cruess, S. R., & Steinert, Y. (2016). ‘Amending Miller’s pyramid to include professional identity formation’. Acad Med, 91(2), pp. 180–185. Etheridge, L. and Boursicot, K. (2013) ‘Performance and workplace assessment’, in Dent, J. A. and Harden, R. M. (eds) A practical guide for medical teachers. 4th edn. London: Elsevier Limited. Kahneman, D. (2011) Thinking, fast and slow. New York: Farrar, Straus and Giroux. Lawshe, CH. (1975) A quantitative approach to content validity. Pers Psychol, 28(4), pp. 563–75. McLean, M. and Gale, R. (2018) Essays and short answer questions. FAIMER-Keele Master’s in Health Professions Education: Accreditation and Assessment. Module 1, Unit 5, 5th edition. FAIMER Centre for Distance Learning, CenMEDIC, London. McManus, IC. Thompson, M. and Mollon, J. (2006) ‘ Assessment of examiner leniency and stringency (‘hawk-dove effect’) in the MRCP(UK) clinical examination (PACES) using multi-facet Rasch modelling’ BMC Med Educ. 42(6) doi:10.1186/1472- 6920-6-42 Merrienboer, J.J.G. (2013) ‘Instructional Design’, in Dent, J. A. and Harden, R. M. (eds) A practical guide for medical teachers. 4th edn. London: Elsevier Limited. Murphy, JM. Seneviratne, R. Remers, O and Davis, M. (2009) ‘Hawks’ and ‘doves’: effect of feedback on grades awarded by supervisors of student selected components, Med Teach, 31(10), e484-e488, DOI: 10.3109/01421590903258670 Norcini, J. and McKinley, D. W. (2007) ‘Assessment methods in medical education’, Teaching and Teacher Education, 23(3), pp. 239–250. doi: 10.1016/j.tate.2006.12.021. Norcini, J. and Troncon, L. (2018) Foundations of assessment. FAIMER-Keele Master’s in Health Professions Education: Accreditation and Assessment. Module 1, Unit 1. 6th edn. London: FAIMER Centre for Distance Learning CenMEDIC. Norcini, J. and McKinley, D. W. (2013) ‘Standard Setting’, in Dent, J. A. and Harden, R. M. (eds) A practical guide for medical teachers. 4th edn. London: Elsevier Limited. Swanson, D. and Case, S. (1998) Constructing written test questions for the basic and clincial sciences. 3rd Ed. National Board of Medical Examiners. 3750 Market Street Philadelphia, PA 19104. Van Der Vleuten, C. Schuwirth, L. Scheele, F. Driessen, E. and Hodges, B. (2010) ‘The assessment of professional competence: building blocks for theory development’, Best Practice & Research Clinical Obstetrics and Gynecology, pp. 1-17. doi:10.1016/j. bpobgyn.2010.04.001 Wenger, E. (1998). Communities of practice: Learning, meaning, and identity. Cambridge university press.

In this study the evolutionary development of orthopedics (management of diseases of bones and joints), which commenced in early Mesopotamia and Egypt, is followed through Classical times.The Greek infl uence probably commenced in the 6thcentury BC with Democedes of Croton who cured the Persian king’s dislocated ankle. The Corpus Hippocraticum laid the foundation of orthopedic practice in antiquity. Although knowledge of anatomy was limited, its four books on orthopedics (The Nature of Bones, Mochlicon, On Fractures, On Joints) count amongst the outstanding contributions of Hippocratic writers. In systematic manner the general recognition and management of fractures and dislocations are covered, followed by the handling of individual lesions. Hippocrates differentiated between closed and open fractures (with overlaying skin wounds). Closed fractures were reduced to as normal a position as possible – manually where possible, but with large bones and in the presence of formidable muscle mass, mechanical traction was often employed (e.g. the Hippocratic bench and the bizarre succusion ladder for spinal deformities). There is no mention of the use of analgetic drugs. After application of cerate (mixture of olive oil, soda and pitch) to the skin, the fracture was immobilized by a combination of plasters and compresses (often fi rmed up with gum-mixtures) – but never very fi rmly. On the 3rd, 6/7th, 9thand 12th days the bandaging was removed, the lesion inspected and if considered necessary, re-aligned, A variety of splints were then applied. Strict bed rest was enforced, as well as a light diet (no wine or meat for 10 days). It was believed that fractures of the feet, clavicle, ribs and jaw healed after 20 days, of the forearm after 30 days, and fractures of the upper arm and leg after 40 days. Open fractures were considered very serious injuries, and reduced very carefully. Protruding bone fragments were removed (sawn off if necessary) and the wound was covered with black cerate, compresses and light bandages. Pressure and heavy splints were thought to induce infection and gangrene and thus avoided. Dislocations were reduced as soon and as effectively as possible, before muscle spasm set in. As with fractures manual reduction was, where necessary, complemented by mechanical traction. After extensive washing of the joint area with warm water, cerate was applied to the wound and specialised bandaging (even splints) ensured immobilization. Open dislocations like open fractures were considered very serious and reduction was not attempted. Again all pressure bandaging was avoided. A non-functional joint was commonly the end result. The management of 18 specifi c fractures is described in detail. Jaw fractures were fi xed by the binding of contiguous teeth. Fractures of the spinal column clearly presented a major problem. Although knowledge of spinal anatomy was surprisingly good, the diagnosis of fractures was very difficult and its association with spinal curvatures presented almost insurmountable problems of management. It was recognized that rib fractures could cause serious damage to the lung and pleura. Complex problems caused by arm fractures involving the elbow or shoulder joints, and combined radius and ulna fractures, are addressed. Femur fractures presented major problems and permanent leg deformity was very common. Open femur fractures were extremely serious and Hippocrates even stated that a physician who could ethically avoid becoming involved in treating such an injury, should do so. Fractures of femur necks were not recognised. The Hippocratic work, Wounds of the head, dealing with fractures of the skull, is not covered in this study.Management of the major joints are individually described. Seven different techniques of reducing a dislocated shoulder joint are mentioned The original description of the management of the dislocation of the wrist and hand is lost. Proper reduction of hip-dislocation was essential to avoid muscle atrophy and life-long limping, and was achieved by intricate mechanical suspension. Strangely enough, lateral dislocation of the knee was a common occurrence and not seen as a serious problem. Congenital club feet were effectively treated by prolonged fi xation in the correct position by way of tight bandaging with compresses stiffened in glue-mixtures.There is abundant skeletal evidence of osteo-arthritis in Neolithic man, but no clear description of it in the Corpus Hippocraticum. Gout is repeatedly mentioned in the Corpus but without detailed descriptions of the disease. In the Roman era authors like Heliodorus, Antyllus and Celsus in particular, wrote authoritatively on orthopedic subjects, Osteo-archaeological evidence is that fractures were treated expertly in the Roman army. Conditions consistent with degenerative osteoarthritis and true gout (as podagra and chiragra) were described by Celsus and Aretaeus of Cappadocia. Soranus, Rufus of Ephesus and Galen also wrote on orthopedic subjects. We will today differ from many statements made in the Corpus Hippocraticum, but it is clear that the orthopedic basis laid by those documents was not seriously challenged for 1 000 years.

AbstractTemporospatial distribution and trends of thunderstorm, hail, gale and heavy precipitation events over the Tibetan Plateau (TP), as well as the associated mechanisms with observational data from 1979-2016 are investigated, which have not been fully studied under a changing climate. The results indicate that thunderstorm, hail and gale events over the whole TP show significant decreasing trends, while heavy precipitation events have an insignificant increasing trend. The southeast (SE) and central south (SC) subregions have obvious significant decreasing trends in thunderstorm, hail and gale events, while the northeast (NE) subregion has a significant increasing trend in heavy precipitation events. It is found that the atmospheric circulation anomaly caused by the northwestern Atlantic Sea Surface Temperature (SST) anomaly associated with the North Atlantic Oscillation (NAO) should be responsible for these changes. A strong wave train triggered by the northwestern Atlantic SST anomaly propagates from the northern Atlantic to East Asia through Europe, and induces a more upper-level warming over the TP and an anomalous anticyclonic circulation near the Lake Baikal, resulting in more stable atmosphere and blocking effect, which forces the mid-latitude westerlies and associated cold air to shift poleward. The weakened cold air advection over the TP decreases the baroclinic instability and convection initiation, and finally causes the significant decreasing trends in severe weather events. On the other hand, the enhanced easterly winds in the southern flank of the anticyclonic circulation can significantly increase the water vapor flux from the eastern boundary of the TP and heavy precipitation events in the NE subregion.