Forced retroevolution of an RNA bacteriophage

The operator hairpin ahead of the replicase gene in RNA bacteriophage MS2 contains overlapping signals for binding the coat protein and ribosomes. Coat protein binding inhibits further translation of the gene and forms the first step in capsid formation. The hairpin sequence was partially randomized to assess the importance of this structure element for the bacteriophage and to monitor alternative solutions that would evolve on the passaging of mutant phages. The evolutionary reconstruction of the operator failed in the majority of mutants. Instead, a poor imitation developed containing only some of the recognition signals for the coat protein. Three mutants were of particular interest in that they contained double nonsense codons in the lysis reading frame that runs through the operator hairpin. The simultaneous reversion of two stop codons into sense codons has a very low probability of occurring. Therefore the phage solved the problem by deleting the nonsense signals and, in fact, the complete operator, except for the initiation codon of the replicase gene. Several revertants were isolated with activities ranging from 1% to 20% of wild type. The operator, long thought to be a critical regulator, now appears to be a dispensable element. In addition, the results indicate how RNA viruses can be forced to step back to an attenuated form.

First-line therapy with latanoprost 0.005% results in improved ocular circulation in newly diagnosed primary open-angle glaucoma patients: a prospective, 6-month, open-label study

Purpose To evaluate the effect of latanoprost 0.005% on the optic nerve head (ONH) and retinal circulation of newly diagnosed and previously untreated primary open-angle glaucoma (POAG) patients. Methods Twenty-two newly diagnosed and previously untreated POAG patients (mean age±SD: 68.38±11.92 years) were included in this longitudinal open-label study. Patients were treated with latanoprost 0.005% once a day. Intraocular pressure (IOP), systemic blood pressure (BP), mean ocular perfusion pressure (MOPP), and ocular perfusion parameters ‘volume’, ‘velocity’, and ‘flow’ measured at the optic nerve head (ONH) and retina by means of Heidelberg Retina Flowmeter system were evaluated during a 6-month follow-up period. Results Treatment with latanoprost 0.005% resulted in a significant decrease in IOP (P<0.0001) and increase in MOPP (P<0.0001). After correcting for changes in MOPP, the blood velocity measured at the ONH level was significantly higher after 6 months of treatment than at baseline (P=0.0310). In addition, blood volume and flow measured at the peripapillary retina level improved after 3 and 6 months of treatment (P=0.0170; P=0.0260, and P=0.0170; P=0.0240 respectively). Conclusion Previously untreated POAG patients exhibit reduced IOP, increased MOPP and improved ocular perfusion at the ONH and retina levels when treated with Latanoprost 0.005%. These effects could be beneficial for glaucoma patients suffering from ocular vascular dysregulation.

A naturally shaped silicone ventricle evaluated in a mock circulation loop: a preliminary study

Mock circulation loops are used to evaluate the performance of cardiac assist devices prior to animal and clinical testing. A compressible, translucent silicone ventricle chamber that mimics the exact size, shape and motion of a failing heart is desired to assist in flow visualization studies around inflow cannulae during VAD support. The aim of this study was therefore to design and construct a naturally shaped flexible left ventricle and evaluate its performance in a mock circulation loop. The ventricle shape was constructed by the use of CT images taken from a patient experiencing cardiomyopathic heart failure and used to create a 3D image and subsequent mould to produce a silicone ventricle. Different cardiac conditions were successfully simulated to validate the ventricle performance, including rest, left heart failure and VAD support.

Flow patterns on sieve trays

Studies into gas-liquid flow patterns were carried out on commercial scale sieve trays where the ratio of froth depth to flow path length is typical of that found in practice. Experiments were conducted on a 2.44 m diameter air-water distillation simulator, in which flow patterns were investigated by direct observation, using directional flow pointers; by water cooling, to simulate mass transfer; and by height of clear liquid measurements across the tray. The flow rates used are typical of those found in practice. The approach adopted was to investigate the effect of the gas flow on the liquid flow by comparing water only flow patterns across an unperforated tray with air-water flow patterns on perforated trays. Initial gas-liquid contacting experiments on the 6.35 mm hole tray showed that, under certain conditions, the gas flow pattern beneath the test tray can have a significant effect on the tray liquid flow pattern such that gas-driven liquid circulation was produced. This was found to be a function of this particular air-water simulator design, and as far as is known this is the first time that this phenomenon has been observed. Consequently non-uniform gas flow effects were removed by modification of the gas distribution system. By eliminating gas circulation effects, the effect of the gas flow on the separation of liquid flow was similar to that obtained on the 1.0 mm hole tray (Hine, 1990). That is, flow separation occurred at the ends of the inlet downcomer which produced large circulating zones along the tray segments both on the non-perforated and perforated trays. The air when forced through the liquid, inhibited circulating flow such that it only occurred at high water inlet velocities. With the 6.35 mm hole tray, the growth and velocity of circulating flow was reduced at high superficial air velocities, and in the experiments to simulate distillation, liquid was in forward flow over most of the tray.

Effect of liquid flow patterns on distillation trays

The thesis describes experimental work on sieve trays in an air-water simulator, 2.44 m in diameter. The liquid flow pattern, for flowrates similar to those used in commercial scale distillation, was observed experimentally by water cooling experiments, in which the temperature of the water is measured at over 100 positions over the tray area. The water is cooled by the rising air which is forced through the tray. A heat and mass transfer analogy is drawn whereby the water temperature is mapped to liquid concentration in mass transfer, and the water temperature profiles reveal how liquid channelling may reduce the tray efficiency. The first experiment was to observe the flow of water only over an unperforated tray. With the exception of very low weir loads, the flow separated at the ends of the inlet downcomer. This caused liquid to flow straight across the tray between the downcomers and large circulating regions to be formed in the side regions of the tray. The effect of the air crossflow on the flow pattern was then observed on a sieve tray of 10% free area with 1 mm diameter holes (such as is used in cryogenic distillation). The flow patterns developed on the tray were similar to those produced with water only on the unperforated tray, but at low weir loads the air crossflow prevented separation of the water flow and the associated circulating regions. At higher weir loads, liquid channelling down the centre of the tray and circulation in the side regions occurred. The percentage of the tray occupied by circulating liquid depended upon the velocity of the liquid entering the tray, which was set by the weir load and size of the gap under the inlet downcomer. The water cooling experiments showed that the temperature of the water in a circulating region is much lower than in other parts of the tray, indicating that the driving force for heat transfer is reduced. In a column section where trays (and circulating areas) are mounted on top of each other, the circulating regions will cause air (or vapour) passing through them to have a reduced change in temperature or concentration leading a loss in tray efficiency.

Sedimentology, palaeontology and diagenesis of the Much Wenlock limestone formation

Lithofacies distribution indicates that the Much Wenlock Limestone Formation of England and South Wales was desposited on a shelf which was flat and gently subsiding in the north, but topographically variable in the south. Limestone deposition in the north began with 12m of alga-rich limestone, which formed an upward shoaling sequence. Deepening then led to deposition of calcareous silty mudstones on the northern shelf. The remainder of the formation in this area formed during a shelf-wide regression, culminating in the production of an E to W younging sandbody. Lithofacies distribution on the southern shelf was primarily controlled by local subsidence. Six bedded lithofacies are recognised which contain 14 brachiopod/bryozoan dominated assemblages, of which 11 are in situ and three consist of reworked fossils. Microfacies analysis is necessary to distinguish assemblages which reflect original communities from those which reflect sedimentary processes. Turbulence, substrate-type, ease of feeding and other organisms in the environment controlled faunal distribution. Reefs were built dominantly by corals, stromatoporoids, algae and crinoids. Coral/stromatoporoid (Type A) reefs are common, particularly on the northern shelf, where they formed in response to shallowing, ultimately growing in front of the advancing carbonate sandbody. Algae dominate Type B and Type C reefs, reflecting growth in areas of poor water circulation. Lithification of the formation began in the marine-phreatic environment with precipitation of aragonite and high Mg calcite, which was subsequently altered to turbid low Mg calcite. Younger clear spars post-date secondary void formation. The pre-compactional clear spars have features which resemble the products of meteoric water diagenesis, but freshwater did not enter the formation at this time. The pre-compactional spars were precipitated by waters forced from the surrounding silty mudstones at shallow burial depths. Late diagenetic products are stylolites, compaction fractures and burial cements.

'Forced to Friendship'? Russian (mis-)understandings of soft power and the implications for audience attraction in Ukraine

This article argues that for all its efforts to implement soft power techniques, the Kremlin still fails to grasp the subtle, voluntaristic essence of soft power. This is reflected in a style of public interaction that has practical implications for how Russian soft power overtures are received by the audience. This is demonstrated through the findings of mixed-method empirical research from four Ukrainian regions. Thus, while surveys show that the worldview promoted by Russian public diplomacy resonates to some extent, insights from focus groups indicate that potential attraction is nevertheless limited by Russia's 'hard' and obtrusive approach to cultural influence.

Stochastically forced dislocation density distribution in plastic deformation

The dynamical evolution of dislocations in plastically deformed metals is controlled by both deterministic factors arising out of applied loads and stochastic effects appearing due to fluctuations of internal stress. Such type of stochastic dislocation processes and the associated spatially inhomogeneous modes lead to randomness in the observed deformation structure. Previous studies have analyzed the role of randomness in such textural evolution but none of these models have considered the impact of a finite decay time (all previous models assumed instantaneous relaxation which is "unphysical") of the stochastic perturbations in the overall dynamics of the system. The present article bridges this knowledge gap by introducing a colored noise in the form of an Ornstein-Uhlenbeck noise in the analysis of a class of linear and nonlinear Wiener and Ornstein-Uhlenbeck processes that these structural dislocation dynamics could be mapped on to. Based on an analysis of the relevant Fokker-Planck model, our results show that linear Wiener processes remain unaffected by the second time scale in the problem but all nonlinear processes, both Wiener type and Ornstein-Uhlenbeck type, scale as a function of the noise decay time τ. The results are expected to ramify existing experimental observations and inspire new numerical and laboratory tests to gain further insight into the competition between deterministic and random effects in modeling plastically deformed samples.