Beta-enolization In Bicyclic Ketones

A variety of bicyclic ketones was prepared and under strongly basic conditions (t-BuOK/t-BuOH/185{dollar}\sp\circ{dollar}C) their behaviour with respect to {dollar}\beta{dollar}-enolization was examined. Several new compounds were produced upon such treatment; these were identified on the basis of their {dollar}\rm\sp{lcub}13{rcub}Cmr{dollar} and {dollar}\rm\sp1Hmr{dollar} spectra.;3,3-Dimethylbicyclo (3.2.2) nonan-2-one slowly rearranged to 3,3-dimethylbicyclo (3.3.1) nonan-2-one, and the latter was stable. Similarly, 3,3-dimethylbicyclo (3.2.2) non-6-en-2-one rearranged to 3,3-dimethylbicyclo (3.3.1) non-6-en-2-one, which was not stable. Experiments with 3,3-dimethylbicyclo (3.3.1) non-6-en-2-one revealed that it was converted into five compounds. The major product, 2,2-dimethyl-4,5,6,7-tetra-hydrindan-1-one, arose from a {dollar}\beta{dollar}-enolate rearrangement. However, this enone underwent slow reduction to cis- and trans-8,8-dimethylbicyclo (4.3.0) nonan-7-one, presumably by single electron transfer from t-BuOK. As a result, the use of a {dollar}\beta{dollar}-enolate rearrangement in natural product synthesis was not considered worthwhile. Also, 3,3,7,7-tetramethylbicyclo- (3.3.1) nonan-2,6-dione was found to be reduced to 6-hydroxy-3,3,7,7-tetramethylbicyclo (3.3.1) nonan-2-one.;3,3-Dimethylbenzobicyclo (3.2.1) - and (2.2.2) octen-2-one and 3,3-dimethylbenzobicyclo (3.2.2) nonen-2-one were prepared and then examined under the same conditions as above. It was found that each rearranged to a single ketone; namely, 3,3-dimethyl-6,7-benzobicyclo (3.3.0) octen-2-one, 7,7-dimethyl-2,3-benzobicyclo (3.2.1) octen-6-one and 3,3-dimethyl-5,6-benzobicyclo (3.3.1) nonen-2-one, respectively. These rearrangement processes, however, are in competition with Haller-Bauer cleavage. The acids resulting from cleavage represented the major products of base treatment. This process precluded synthetic applications of {dollar}\beta{dollar}-enolate rearrangement in these systems.;The highly hindered alkoxide base, potassium 3-ethyl-3-pentoxide was prepared in an effort to retard the cleavage pathway, and while rearrangement was still observed, a predominance of cleavage products was again noted. The effect of several amide bases on the homoenolization of a variety of hindered ketones was also undertaken, in the hope of eliminating reduction caused by t-BuOK. Based on the results of this study, only N-lithio-9-azabicyclo (3.3.1) nonane (LABN) appeared to be worthy of further study, although for the systems studied herein, {dollar}\beta{dollar}-enolization was not observed when LABN was used as base

A bonding and damage constitutive model for lightly cemented granular material

The behaviour of cemented granular material is complicated by the fact that the eventual cemented properties depend on the conditions under which cement hydration (curing) takes place. There are a number of situations in industry where granular materials are mixed with small quantities of cement and deployed in highly transient curing environments. Understanding and predicting the responses in these situations requires a constitutive model where cemented properties are an output, rather than a pre-determined input. This paper presents a constitutive model that is capable of representing the formation and destruction of bonding in weakly cemented granular material in a transient stress environment.</p

The potential impact of technological innovation on the aquaculture industry

From Executive Summary: Farming of the sea has a long history in many countries, essentially based on a range of modified low-input natural systems, including ponds, shellfish beds and simple enclosures or cages. In the last two decades the intensive farming of marine fish and the scaling up of shellfish culture has been a major trend, prompted by rising demand for aquatic food products precisely when traditional supplies from capture fisheries are in steep decline

The future of the global food system

Although food prices in major world markets are at or near a historical low, there is increasing concern about food security—the ability of the world to provide healthy and environmentally sustainable diets for all its peoples. This article is an introduction to a collection of reviews whose authors were asked to explore the major drivers affecting the food system between now and 2050. A first set of papers explores the main factors affecting the demand for food (population growth, changes in consumption patterns, the effects on the food system of urbanization and the importance of understanding income distributions) with a second examining trends in future food supply (crops, livestock, fisheries and aquaculture, and ‘wild food’). A third set explores exogenous factors affecting the food system (climate change, competition for water, energy and land, and how agriculture depends on and provides ecosystem services), while the final set explores cross-cutting themes (food system economics, food wastage and links with health). Two of the clearest conclusions that emerge from the collected papers are that major advances in sustainable food production and availability can be achieved with the concerted application of current technologies (given sufficient political will), and the importance of investing in research sooner rather than later to enable the food system to cope with both known and unknown challenges in the coming decades

The SSTARS (STeroids and Stents Against Re-Stenosis) Trial : different stent alloys and the use of peri-procedural oral corticosteroids to prevent in-segment restenosis after percutaneous coronary intervention

Background Stent design and technological modifications to allow for anti-proliferative drug elution influence restenosis rates following percutaneous coronary intervention (PCI). We aimed to investigate whether peri-procedural administration of corticosteroids or the use of thinner strut cobalt alloy stents would reduce rates of binary angiographic restenosis (BAR) after PCI. Methods This was a two centre, mixed single and double blinded, randomised controlled trial using a factorial design. We compared (a) the use of prednisolone to placebo, starting at least six hours pre-PCI and continued for 28 days post-PCI, and (b) cobalt chromium (CoCr) to stainless steel (SS) alloy stents, in patients admitted for PCI. The primary end-point was BAR at six months. Results 315 patients (359 lesions) were randomly assigned to either placebo (n = 145) or prednisolone (n = 170) and SS (n = 160) or CoCr (n = 160). The majority (58%) presented with an ACS, 11% had diabetes and 287 (91%) completed angiographic follow up. BAR occurred in 26 cases in the placebo group (19.7%) versus 31 cases in the prednisolone group (20.0%) respectively, p = 1.00. For the comparison between SS and CoCr stents, BAR occurred in 32 patients (21.6%) versus 25 patients (18.0%) respectively, p = 0.46. Conclusion Our study showed that treating patients with a moderately high dose of prednisolone for 28 days following PCI with BMS did not reduce the incidence of BAR. In addition, we showed no significant reduction in 6 month restenosis rates with stents composed of CoCr alloy compared to SS

Pellino-1 Regulates the Responses of the Airway to Viral Infection

Exposure to respiratory pathogens is a leading cause of exacerbations of airway diseases such as asthma and chronic obstructive pulmonary disease (COPD). Pellino-1 is an E3 ubiquitin ligase known to regulate virally-induced inflammation. We wished to determine the role of Pellino-1 in the host response to respiratory viruses in health and disease. Pellino-1 expression was examined in bronchial sections from patients with GOLD stage two COPD and healthy controls. Primary bronchial epithelial cells (PBECs) in which Pellino-1 expression had been knocked down were extracellularly challenged with the TLR3 agonist poly(I:C). C57BL/6 Peli1-/- mice and wild type littermates were subjected to intranasal infection with clinically-relevant respiratory viruses: rhinovirus (RV1B) and influenza A. We found that Pellino-1 is expressed in the airways of normal subjects and those with COPD, and that Pellino-1 regulates TLR3 signaling and responses to airways viruses. In particular we observed that knockout of Pellino-1 in the murine lung resulted in increased production of proinflammatory cytokines IL-6 and TNFα upon viral infection, accompanied by enhanced recruitment of immune cells to the airways, without any change in viral replication. Pellino-1 therefore regulates inflammatory airway responses without altering replication of respiratory viruses.</p

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Using surveillance data to determine treatment rates and outcomes for patients with chronic hepatitis C virus infection

The aim of this work was to develop and validate an algorithm to monitor rates of, and response to, treatment of patients infected with hepatitis C virus (HCV) across England using routine laboratory HCV RNA testing data. HCV testing activity between January 2002 and December 2011 was extracted from the local laboratory information systems of a sentinel network of 23 laboratories across England. An algorithm based on frequency of HCV RNA testing within a defined time period was designed to identify treated patients. Validation of the algorithm was undertaken for one center by comparison with treatment data recorded in a clinical database managed by the Trent HCV Study Group. In total, 267,887 HCV RNA test results from 100,640 individuals were extracted. Of these, 78.9% (79,360) tested positive for viral RNA, indicating an active infection, 20.8% (16,538) of whom had a repeat pattern of HCV RNA testing suggestive of treatment monitoring. Annual numbers of individuals treated increased rapidly from 468 in 2002 to 3,295 in 2009, but decreased to 3,110 in 2010. Approximately two thirds (63.3%; 10,468) of those treated had results consistent with a sustained virological response, including 55.3% and 67.1% of those with a genotype 1 and non-1 virus, respectively. Validation against the Trent clinical database demonstrated that the algorithm was 95% sensitive and 93% specific in detecting treatment and 100% sensitive and 93% specific for detecting treatment outcome. Conclusions: Laboratory testing activity, collected through a sentinel surveillance program, has enabled the first country-wide analysis of treatment and response among HCV-infected individuals. Our approach provides a sensitive, robust, and sustainable method for monitoring service provision across Englan

Language-free graphical signage improves human performance and reduces anxiety when working collaboratively with robots

As robots become more ubiquitous, and their capabilities extend, novice users will require intuitive instructional information related to their use. This is particularly important in the manufacturing sector, which is set to be transformed under Industry 4.0 by the deployment of collaborative robots in support of traditionally low-skilled, manual roles. In the first study of its kind, this paper reports how static graphical signage can improve performance and reduce anxiety in participants physically collaborating with a semi-autonomous robot. Three groups of 30 participants collaborated with a robot to perform a manufacturing-type process using graphical information that was relevant to the task, irrelevant, or absent. The results reveal that the group exposed to relevant signage was significantly more accurate in undertaking the task. Furthermore, their anxiety towards robots significantly decreased as a function of increasing accuracy. Finally, participants exposed to graphical signage showed positive emotional valence in response to successful trials. At a time when workers are concerned about the threat posed by robots to jobs, and with advances in technology requiring upskilling of the workforce, it is important to provide intuitive and supportive information to users. Whilst increasingly sophisticated technical solutions are being sought to improve communication and confidence in human-robot co-working, our findings demonstrate how simple signage can still be used as an effective tool to reduce user anxiety and increase task performance