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1.
Aims Our aim is to reconstruct decadal scale development of historical landscapes during the last 1000 years by means of fossil pollen analysis of annually laminated lake sediments, and detailed historical maps and documents. Location Lake Rõuge Tõugjärv (Estonia), a small lake with annually laminated lake sediments situated in a dense prehistoric setting. Methods The chronology of the palaeodata is based on the annual laminations supported by AMS 14C and 210Pb dating and 137Cs, 241Am, and spheroidal carbonaceous particle marker horizons. The time‐scale and resolution allows fine sampling (the pollen samples generally comprise 3.5 years) and vegetation change reconstruction. Relevant source area of pollen (RSAP) of the lake was estimated, and the statistical zonation, rate of change, palynological richness, and DCA and PCA ordinations were generated on the basis of the pollen data. The historical calibration data set (maps, numerical information on population, domestic stock, farmland division, etc.) is based on archival material preserved in the Estonian Historical Archives. Results The topmost part (0–180 cm) of the sediment column of Lake Rõuge Tõugjärv, covering the last 1000 years, is visibly laminated carbonaceous gyttja. The varve chronology extends from ad 2000 to ad 1339, with a cumulative ± 9‐year error estimate. Beyond this the chronology is extrapolated using the 14C date and varve age–depth estimations. The simulation of the RSAP of Lake Tõugjärv shows that the major portion of the pollen loading originating from local vegetation is derived from plants growing within 2000 m of the sampling site. The pollen record divides into five statistically significant subgroups, which fall on the PCA plot into three clusters reflecting the general openness–closedness of the landscape. During the period between ad 1000 and 1200 (RT 1) the Rõuge area was generally wooded with birch, spruce and pine forests. The advancement of extensive farming gradually opened up the landscape between ad 1200 and 1650 (RT 2 and RT 3). The maximum openness of the landscape was reached between ad 1650 and 1875 (RT 4), with the most open period in the late eighteenth century. Historical maps from 1684 and 1870–99 and available quantitative data on population, domestic stock, farmland division, etc. show the same trend. The pollen data covering the last 125 years, and maps from 1935 and 1995, show the reduction of arable land in RSAP of the lake under investigation and the reduction of open land to an extent comparable with the end of the seventeenth century. Main conclusions The formation and development of the cultural landscape at Rõuge over the last 1000 years is characterized by rapid changes in floristic richness and rates of vegetation change attributed to certain historic processes in the RSAP. Five phases of landscape and social development are clearly distinguished during the last 1000 years. The decadal scale vegetation response to human‐induced forcing agrees with historical maps and documents and could be used for past landscapes prior to the period with solid historical data.  相似文献   
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Vertebrate fossils from many different formations fluoresce when exposed to ultraviolet (UV) light. In this paper field observations and controlled experiments in the Chadron Formation (White River Group, late Eocene) of Wyoming are used to assess the utility of searching for fossils at night using ultraviolet light. The results indicate that, especially for very small teeth and egg-shell fragments, searching with ultraviolet light at night can result in significantly more specimens than searching during daylight hours. This method has the potential to increase sample sizes for small vertebrate specimens that are often overlooked when using standard collecting techniques.  相似文献   
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Mass drug administration (MDA) with antibiotics is a key component of the SAFE strategy for trachoma control. Guidelines recommend that where MDA is warranted the whole population be targeted with 80% considered the minimum acceptable coverage. In other countries, MDA is usually conducted by salaried Ministry of Health personnel (MOH). In Plateau State, Nigeria, the existing network of volunteer Community Directed Distributors (CDD) was used for the first trachoma MDA. We conducted a population-based cluster random survey (CRS) of MDA participation to determine the true coverage and compared this to coverage reported from CDD registers. We surveyed 1,791 people from 352 randomly selected households in 24 clusters in three districts in Plateau State in January 2011, following the implementation of MDA. Households were enumerated and all individuals present were asked about MDA participation. Household heads were questioned about household-level characteristics and predictors of participation. Individual responses were compared with the CDD registers. MDA coverage was estimated as 60.3% (95% CI 47.9–73.8%) by the survey compared with 75.8% from administrative program reports. CDD registration books for comparison with responses were available in 19 of the 24 clusters; there was a match for 658/682 (96%) of verifiable responses. CDD registers did not list 481 (41.3%) of the individuals surveyed. Gender and age were not associated with individual participation. Overall MDA coverage was lower than the minimum 80% target. The observed discrepancy between the administrative coverage estimate from program reports and the CRS was largely due to identification of communities missed by the MDA and not reported in the registers. CRS for evaluation of MDA provides a useful additional monitoring tool to CDD registers. These data support modification of distributor training and MDA delivery to increase coverage in subsequent rounds of MDA.  相似文献   
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Polycomb-repressive complex 1 (PRC1)-mediated histone ubiquitylation plays an important role in aberrant gene silencing in human cancers and is a potential target for cancer therapy. Here we show that 2-pyridine-3-yl-methylene-indan-1,3-dione (PRT4165) is a potent inhibitor of PRC1-mediated H2A ubiquitylation in vivo and in vitro. The drug also inhibits the accumulation of all detectable ubiquitin at sites of DNA double-strand breaks (DSBs), the retention of several DNA damage response proteins in foci that form around DSBs, and the repair of the DSBs. In vitro E3 ubiquitin ligase activity assays revealed that PRT4165 inhibits both RNF2 and RING 1A, which are partially redundant paralogues that together account for the E3 ubiquitin ligase activity found in PRC1 complexes, but not RNF8 nor RNF168. Because ubiquitylation is completely inhibited despite the efficient recruitment of RNF8 to DSBs, our results suggest that PRC1-mediated monoubiquitylation is required for subsequent RNF8- and/or RNF168-mediated polyubiquitylation. Our results demonstrate the unique feature of PRT4165 as a novel chromatin-remodeling compound and provide a new tool for the inhibition of ubiquitylation signaling at DNA double-strand breaks.  相似文献   
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Inhibition of mPGES-1, the terminal enzyme in the arachidonic acid/COX pathway to regulate the production of pro-inflammatory prostaglandin PGE2, is considered an attractive new therapeutic target for safe and effective anti-inflammatory drugs. The discovery of a novel series of orally active, selective benzoxazole piperidinecarboxamides as mPGES-1 inhibitors is described. Structure–activity optimization of lead 5 with cyclohexyl carbinols resulted in compound 12, which showed excellent in vitro potency and selectivity against COX-2, and reasonable pharmacokinetic properties. Further SAR studies of the benzoxazole ring substituents lead to a novel series of highly potent compounds with improved PK profile, including 23, 26, and 29, which were effective in a carrageenan-stimulated guinea pig air pouch model of inflammation. Based on its excellent in vitro and in vivo pharmacological, pharmacokinetic and safety profile and ease of synthesis, compound 26 (PF-4693627) was advanced to clinical studies.  相似文献   
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Purpose

A life cycle assessment was conducted to determine a baseline for environmental impacts of cheddar and mozzarella cheese consumption. Product loss/waste, as well as consumer transport and storage, is included. The study scope was from cradle-to-grave with particular emphasis on unit operations under the control of typical cheese-processing plants.

Methods

SimaPro© 7.3 (PRé Consultants, The Netherlands, 2013) was used as the primary modeling software. The ecoinvent life cycle inventory database was used for background unit processes (Frischknecht and Rebitzer, J Cleaner Prod 13(13–14):1337–1343, 2005), modified to incorporate US electricity (EarthShift 2012). Operational data was collected from 17 cheese-manufacturing plants representing 24 % of mozzarella production and 38 % of cheddar production in the USA. Incoming raw milk, cream, or dry milk solids were allocated to coproducts by mass of milk solids. Plant-level engineering assessments of allocation fractions were adopted for major inputs such as electricity, natural gas, and chemicals. Revenue-based allocation was applied for the remaining in-plant processes.

Results and discussion

Greenhouse gas (GHG) emissions are of significant interest. For cheddar, as sold at retail (63.2 % milk solids), the carbon footprint using the IPCC 2007 factors is 8.60 kg CO2e/kg cheese consumed with a 95 % confidence interval (CI) of 5.86–12.2 kg CO2e/kg. For mozzarella, as sold at retail (51.4 % milk solids), the carbon footprint is 7.28 kg CO2e/kg mozzarella consumed, with a 95 % CI of 5.13–9.89 kg CO2e/kg. Normalization of the results based on the IMPACT 2002+ life cycle impact assessment (LCIA) framework suggests that nutrient emissions from both the farm and manufacturing facility wastewater treatment represent the most significant relative impacts across multiple environmental midpoint indicators. Raw milk is the major contributor to most impact categories; thus, efforts to reduce milk/cheese loss across the supply chain are important.

Conclusions

On-farm mitigation efforts around enteric methane, manure management, phosphorus and nitrogen runoff, and pesticides used on crops and livestock can also significantly reduce impacts. Water-related impacts such as depletion and eutrophication can be considered resource management issues—specifically of water quantity and nutrients. Thus, all opportunities for water conservation should be evaluated, and cheese manufacturers, while not having direct control over crop irrigation, the largest water consumption activity, can investigate the water use efficiency of the milk they procure. The regionalized normalization, based on annual US per capita cheese consumption, showed that eutrophication represents the largest relative impact driven by phosphorus runoff from agricultural fields and emissions associated with whey-processing wastewater. Therefore, incorporating best practices around phosphorous and nitrogen management could yield improvements.  相似文献   
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