Synthetic RNA modules for fine-tuning gene expression levels in yeast by modulating RNase III activity

The design of synthetic gene networks requires an extensive genetic toolbox to control the activities and levels of protein components to achieve desired cellular functions. Recently, a novel class of RNA-based control modules, which act through post-transcriptional processing of transcripts by directed RNase III (Rnt1p) cleavage, were shown to provide predictable control over gene expression and unique properties for manipulating biological networks. Here, we increase the regulatory range of the Rnt1p control elements, by modifying a critical region for enzyme binding to its hairpin substrates, the binding stability box (BSB). We used a high throughput, cell-based selection strategy to screen a BSB library for sequences that exhibit low fluorescence and thus high Rnt1p processing efficiencies. Sixteen unique BSBs were identified that cover a range of protein expression levels, due to the ability of the sequences to affect the hairpin cleavage rate and to form active cleavable complexes with Rnt1p. We further demonstrated that the activity of synthetic Rnt1p hairpins can be rationally programmed by combining the synthetic BSBs with a set of sequences located within a different region of the hairpin that directly modulate cleavage rates, providing a modular assembly strategy for this class of RNA-based control elements

Shipping as a Knowledge Industry: Research and Strategic Planning at Ocean Group

This chapter approaches the question of how transformations in the world of shipping relate to wider trends in business and general history through the lens of knowledge. It will investigate how technological and managerial knowledge was created, developed and exploited as a corporate resource from the 1950s onwards in Ocean Transport and Trading, one of the UK’s leading liner shipping firms. The chapter will, first, briefly discuss the resource-based view of the firm and the importance of knowledge as a corporate resource. It will then examine Ocean’s use of technological and operational knowledge in the post-war era. The following section examines the introduction of modern management concepts at Ocean from the late 1960s and their impact on corporate strategy. In conclusion, the chapter will argue that the introduction of managerial concepts of knowledge contributed to Ocean’s gradual withdrawal from shipping and transformation into a provider of global logistics services and that analyzing shipping as a knowledge industry helps make sense of the transformation of the industry

Habit and climate change

Many climate-relevant behaviours are habitual. Habits are memory-based propensities to respond automatically to specific cues, acquired by repetition of behaviours in stable contexts. Socio-cognitive models are widely used to predict climate-relevant behaviours; but by positing behaviour as intentional, provide a poor account of habitual behaviours. While unsustainable habits are barriers to change, their very features (frequency and resistance to change) also make them desirable for sustainable behaviours to obtain. While informational approaches are generally ineffective for breaking habits; legislation, incentives, ‘nudges’, implementation intentions, competitions, and ‘moments of change’ (e.g., moving house) are more effective. Linking behaviour to identity and a stable context can ensure new habits endure. Psychological theories and policy efficacy can be greatly improved by attention to habits

Assessment of cardiac remodeling in asymptomatic mitral regurgitation for surgery timing: a comparative study of echocardiography and magnetic resonance imaging

<p>Abstract</p> <p>Background</p> <p>Early surgery is recommended for asymptomatic severe mitral regurgitation (MR), because of increased postoperative left ventricular (LV) dysfunction in patients with late surgery. On the other hand, recent reports emphasized a "watchful waiting" process for the determination of the proper time of mitral valve surgery. In our study, we compared magnetic resonance imaging (MRI) and transthoracic echocardiography to evaluate the LV and left atrial (LA) remodeling; for better definitions of patients that may benefit from early valve surgery.</p> <p>Methods</p> <p>Twenty-one patients with moderate to severe asymptomatic MR were evaluated by echocardiography and MRI. LA and LV ejection fractions (EFs) were calculated by echocardiography and MRI. Pulmonary veins (PVs) were measured from vein orifices in diastole and systole from the tangential of an imaginary circle that completed LA wall. Right upper PV indices were calculated with the formula; (Right upper PV diastolic diameter- Right upper PV systolic diameter)/Right upper PV diastolic diameter.</p> <p>Results</p> <p>In 9 patients there were mismatches between echocardiography and MRI measurements of LV EF. LV EFs were calculated ≥60% by echocardiography, meanwhile < 60% by MRI in these 9 patients. Severity of MR evaluated by effective regurgitant orifice area (EROA) didn't differ with preserved and depressed EFs by MRI (p > 0.05). However, both right upper PV indices (0.16 ± 0.06 vs. 0.24 ± 0.08, p: 0.024) and LA EFs (0.19 ± 0.09 vs. 0.33 ± 0.14, p: 0.025) were significantly decreased in patients with depressed EFs when compared to patients with normal EFs.</p> <p>Conclusions</p> <p>MRI might be preferred when small changes in functional parameters like LV EF, LA EF, and PV index are of clinical importance to disease management like asymptomatic MR patients that we follow up for appropriate surgery timing.</p

The Saccadic and Neurological Deficits in Type 3 Gaucher Disease

Our objective was to characterize the saccadic eye movements in patients with type 3 Gaucher disease (chronic neuronopathic) in relationship to neurological and neurophysiological abnormalities. For approximately 4 years, we prospectively followed a cohort of 15 patients with Gaucher type 3, ages 8–28 years, by measuring saccadic eye movements using the scleral search coil method. We found that patients with type 3 Gaucher disease had a significantly higher regression slope of duration vs amplitude and peak duration vs amplitude compared to healthy controls for both horizontal and vertical saccades. Saccadic latency was significantly increased for horizontal saccades only. Downward saccades were more affected than upward saccades. Saccade abnormalities increased over time in some patients reflecting the slowly progressive nature of the disease. Phase plane plots showed individually characteristic patterns of abnormal saccade trajectories. Oculo-manual dexterity scores on the Purdue Pegboard test were low in virtually all patients, even in those with normal cognitive function. Vertical saccade peak duration vs amplitude slope significantly correlated with IQ and with the performance on the Purdue Pegboard but not with the brainstem and somatosensory evoked potentials. We conclude that, in patients with Gaucher disease type 3, saccadic eye movements and oculo-manual dexterity are representative neurological functions for longitudinal studies and can probably be used as endpoints for therapeutic clinical trials

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Eukaryotic systems broaden the scope of synthetic biology

Synthetic biology aims to engineer novel cellular functions by assembling well-characterized molecular parts (i.e., nucleic acids and proteins) into biological “devices” that exhibit predictable behavior. Recently, efforts in eukaryotic synthetic biology have sprung from foundational work in bacteria. Designing synthetic circuits to operate reliably in the context of differentiating and morphologically complex cells presents unique challenges and opportunities for progress in the field. This review surveys recent advances in eukaryotic synthetic biology and describes how synthetic systems can be linked to natural cellular processes in order to manipulate cell behavior and to foster new discoveries in cell biology research