Microwave-assisted synthesis of a MK2 inhibitor by Suzuki-Miyaura coupling for study in Werner syndrome cells

Microwave-assisted Suzuki-Miyaura cross-coupling reactions have been employed towards the synthesis of three different MAPKAPK2 (MK2) inhibitors to study accelerated aging in Werner syndrome (WS) cells, including the cross-coupling of a 2-chloroquinoline with a 3-pyridinylboronic acid, the coupling of an aryl bromide with an indolylboronic acid and the reaction of a 3-amino-4-bromopyrazole with 4-carbamoylphenylboronic acid. In all of these processes, the Suzuki-Miyaura reaction was fast and relatively efficient using a palladium catalyst under microwave irradiation. The process was incorporated into a rapid 3-step microwave-assisted method for the synthesis of a MK2 inhibitor involving 3-aminopyrazole formation, pyrazole C-4 bromination using N-bromosuccinimide (NBS), and Suzuki-Miyaura cross-coupling of the pyrazolyl bromide with 4-carbamoylphenylboronic acid to give the target 4-arylpyrazole in 35% overall yield, suitable for study in WS cells

Year class strengths of perch and pike in Windermere

The pike (Esox lucius) year classes are more stable than those of the perch (Perca fluviatilis), and have been shown to be closely correlated with temp conditions during the first few months of life. The perch year class strengths have been more variable; for success they require the presence of several positive conditions and the absence of many adverse conditions which could cause failure, a favourable combination of circumstances rarely occurs. The conclusions refer only to Windermere from 1941-1964

The effect of RO3201195 and a pyrazolyl ketone P38 MAPK inhibitor library on the proliferation of Werner syndrome cells

No description supplie

Surface water temperature of Windermere. Monthly and yearly totals of degree-days centigrade and monthly mean temperatures, 1933 to 1975

The surface temperature of Windermere has been recorded by the staff of the Freshwater Biological Association on every weekday (with a few minor exceptions) since 11 January 1933. This publication presents this information in a form which can easily be used by individual research workers. There are 43 tables (1 for each year, 1933-1975) which give the data, expressed as degree-days centigrade. The tables show for each month the number of degree-days above each temperature from 0 degree C to the highest recorded, at 1 degree C intervals. Mean temperatures are obtained by dividing the number of degree-days over 0 degree C by the relevant number of days. The advantage of degree-days rather than mean temperatures is that degree-days are additive so data for any desired periods may be combined quickly and simply. Seasonal results for spring, summer, autumn and winter are presented in tabular form, as are selected totals for comparisons between years. Further tables give the mean temperature in each month of the year, and the frequency distributions of monthly mean temperatures

Soil acidity and eastern wheatbelt plant nutrition.

1. Affects of soil acidity on subterranean clover growth in the cropping areas of Western Australia. Trial 87AL35, 87NO2, 87No3, 88NO76, 88NO77, 88TS54 To investigate the responsiveness to lime of subterranean clover based pastures on acid soil and the cropping areas of Western Australia.To determine the reasons for responses to line in the field, particularly the possible involvement of legume nodulation effects and the alleviation of soil/water repellence.To develop practical identification and management strategies for acid soils problems. Trial 87AL35. Liming in crop/pasture rotation on acid soils Location: Woogenellup. History: 1987 Lime applied, sown to barley 1988 Clover regenerated. Lime increased October production by 10%. 1989 Sown to oats - before being sown pasture growth was measured. Trial 87NO2. Lime in crop/pasture rotations on acid soils. Location: York History 1987 Lime applied and Dalkeith sub. clover sown. No response. 1988 Wheat 1989 Sub clover regenerated. Trial 87NO3 Lime in crop/pasture rotations on acid soils. Location: Grass Valley History 1987 Lime applied and Dalkeith sub. clover sown. Small response to lime. 1988 Wheat. 1989 Sub. clover regenerated. Trial 88NO76 Lime in crop/pasture rotations on acid soils. Location: Goomalling. History 1988 Lime applied and sub.clover sown. 1989 Sown to wheat. Before cropping pasture growth was measured. Trial 88NO77 Lime in crop/pasture rotation on acid soils Location: East Ejanding History: 1988 Lime applied and sub clover sown 1989 Sown to wheat. Before cropping, pasture growth was observed. Trial 88TS54 Lime in crop/pasture rotations on acid soils. Location: Three Springs. History: 1988 Lime applied and sub. clover sown. Lime increased September dry matter by 65%. 1989 Sown to wheat. Before cropping pasture, growth was measured. Trial 88ME102 The interaction of lime and nitrogen in a lupin/wheat rotation. Location: Corrigin Hisory: 1987 Lupins with Super, Cu Zn Mo. 1988 Lime applied, sown to wheat with rates of nitrogen. 1989 Apr. early Super (100 kg/ha) topdressed. Also added Simazine Brodal Sertin and Fusilade. No visual response in July and September. September - Sampled 20 plants per plot, reps 1 and 2, just prior to flowering. Trial 88ME103 The effect of lime in a lupin/cereal rotation. Location: Corrigin. History: 1987 Lupins with Super Cu Zn Mo. 1988 Lime applied, sown to five wheat varieties. 1989 As for 88ME102 (Interaction of lime and nitrogen in a lupin/wheat rotation).\u27 Trial 80M30 Effect of lime on wheat/lupin rotations on acid, eastern wheatbelt yellow sandplain soil. Location: Merredin Research Station. History: Between 1980 and 1989 Lime (Wheat/Clover) x 2 Molybdenum rates. Wheat plots sown to wheat. Clover to triticale. Added 200 g Super/ha, 90 g Mo/ha and 73 kg Agran/ha. yielded 1.5 t/ha. No lime response.Lime increased grain yield in 1986. Sown Wheat and Yorrel, September 1989 sampled 30 plants/plot rep 1 only. November 1989 Harvested. Trial 8OM31 Lime applications in a wheat/lupin rotation. Location: Merredin Research Station. The large effect of lime on wheat yield (75% increase) does not appear to be due to the alleviation of a molybdenum deficiency. the molybdenum treatment is confounded with rate of Agras. A slightly higher rate of Agras was applied in the nil molybdenum plots compared to plus molybdenum plots (123 kg/ha). Trial 88NA82 The effect of lime on gegenerating clover. Location: Yealering. History: Between 1986 and 1989 pasture was very clover dominant Crop sown with 90 kg/ha DAP appeared very N deficient. (cereal variety trial). Rates of lime applied, cultivated and sown to sub. clover Topdressed 210 kg super/ha and 90 KG KC1/ha. Cultivated. Sown to Dalyup Oates with double super (70 kg/ha( and Agran (60 kg/ha). Then harvested. Trial 89ME62 Demonstratino of liming recommendations. Location: Bruce Rock History: 1989 Topdressed lime. Cultivated across pots with cone seeder to 6 cm. Sown to Gutha (50 kg/ha) with super Cu Zn Mo, rates of nitrogen (topdressed). Sprayseed (1.5 L/ha) Brominil M (1 L/ha) and Hoegrass (1 L/ha) No lime response visible. Sampled 50 plants/plot, anthesis. Trial 89ME92, 89ME93, 89ME94. 89MO50 Gypsum for amelioration of acid soils. Location: Burracoppin, N.W. Trayning, Welbungin, Dalwallin

Database Web Programming

This book is the result of teaching the laboratory component of an introductory course in Database Systems in the Department of Computer Science & Software Engineering, Concordia University, Montreal.. The intent of this part of the course was to have the students create a practical web-based application wherein the database forms the dynamic component of a real life application using a web browser as the user interface. It was decided to use all open source software, namely, Apache web server, PHP, JavaScript and HTML, and also the open source database which started as MySQL and has since migrated to MariaDB. The examples given in this book have been run successfully both using MySQL on a Windows platform and MariaDB on a Linux platform without any changes. However, the code may need to be updated as the underlying software systems evolve with time, as functions are deprecated and replaced by others. Hence the user is responsible for making any required changes to any code given in this book. The readers are also warned of the changing privacy and data usage policy of most web sites. They should be aware that most web sites collect and mine user’s data for private profit. The authors wish to acknowledge the contribution of many students in the introductory database course over the years whose needs and the involvement of one of the authors in the early days of the web prompted the start of this project in the late part of the 20th century. This was the era of the dot com bubble. The corporations that survived this bubble have grown, thanks to data and its mining, to become the most powerful monopolies in the history of mankind. It is hoped that the open source community will replace these with locally controlled alternatives

The effect of small-molecule inhibition of MAPKAPK2 on cell ageing phenotypes of fibroblasts from human Werner syndrome

Fibroblasts derived from the progeroid Werner syndrome (WS) show reduced replicative lifespan and a “stressed” morphology, both phenotypes being alleviated by using the p38 MAP kinase inhibitor SB203580. Because p38 is a major hub for the control of stress-signalling pathways we were interested in examining the possible role for downstream kinases in order to refine our understanding of the role of p38 signalling in regulation of WS cell growth. To this end we treated WS and normal fibroblasts with MK2 inhibitors to determine whether MK2 inhibition would affect either the growth or morphology of WS cells. The first inhibitor, 7,8-dihydroxy-2,4-diamino-3- cyanobenzopyranopyridine (inhibitor 2), resulted in inhibition of WS cell growth and had no effect on morphology, effects that occurred below the level needed to inhibit MK2 and thus suggestive of inhibitor toxicity. The second inhibitor, 2-(2-quinolin-3-ylpyridin-4-yl)-1,5,6,7-tetrahydro-4H-pyrrolo-[3,2-c]pyridin-4-one (CMPD16), resulted in a significant extension of WS fibroblast replicative capacity compared to normal cells. In addition, CMPD16 reverted the WS cellular morphology to that seen in normal dermal fibroblasts. These data suggest that MK2 activity plays a substantial role in proliferation control in WS cells. CMPD16 was not as effective in cellular lifespan extension as SB203580, however, suggesting that, although MK2 is a downstream kinase involved in cell cycle arrest, other p38 targets may play a role. Alternatively, as CMPD16 is toxic to cell growth at levels just above those that extend lifespan, it is possible that the therapeutic window is too small. However, as CMPD16 does show significant effects in WS fibroblasts, this acts as proof-of-principle for the efforts to design and synthesise improved MK2 inhibitors. As MK2 is involved in inflammatory processes and inflammation plays a major role in WS phenotypes, these data suggest MK2 as a potential therapeutic target for the treatment of Werner syndrome

Cube law, condition factor and weight-length relationships: history, meta-analysis and recommendations

This study presents a historical review, a meta-analysis, and recommendations for users about weight–length relationships, condition factors and relative weight equations. The historical review traces the developments of the respective concepts. The meta-analysis explores 3929 weight–length relationships of the type W = aLb for 1773 species of fishes. It shows that 82% of the variance in a plot of log a over b can be explained by allometric versus isometric growth patterns and by different body shapes of the respective species. Across species median b = 3.03 is significantly larger than 3.0, thus indicating a tendency towards slightly positive-allometric growth (increase in relative body thickness or plumpness) in most fishes. The expected range of 2.5 < b < 3.5 is confirmed. Mean estimates of b outside this range are often based on only one or two weight–length relationships per species. However, true cases of strong allometric growth do exist and three examples are given. Within species, a plot of log a vs b can be used to detect outliers in weight–length relationships. An equation to calculate mean condition factors from weight–length relationships is given as Kmean = 100aLb−3. Relative weight Wrm = 100W/(amLbm) can be used for comparing the condition of individuals across populations, where am is the geometric mean of a and bm is the mean of b across all available weight–length relationships for a given species. Twelve recommendations for proper use and presentation of weight–length relationships, condition factors and relative weight are given

Interaction in online postgraduate learning:What makes a good forum?

Online postgraduate courses for professionals often use discussion forums to promote engagement and interaction. Equivalency theorem suggests that student-student interaction may increase satisfaction but is not necessary for achieving desired learning outcomes. Therefore, costs, as well as benefits, should be ascertained. We used data from student feedback and interviews to assess the perceptions of part-time postgraduate distance learners, and analyze their views of the role, benefits, and drawbacks of discussion forums. The aim was to assess forum efficacy in the context of the specific needs of these learners, to inform forum use and design. Thematic analysis revealed complex interactions between student context and experience, forum design and management. Structurally tweaking forums to control engagement may be particularly ineffective, stimulating unhelpful grade-focused participation and highlighting forum opportunity costs. The study revealed the importance of designing and managing forums, with direct reference to their costs and benefits for specific student groups