Effects of phosphorylation on ion channel function

There is considerable evidence suggesting that intracellular second messengers can modulate the activity of ion channels, and that protein phosphorylation by the different protein kinases is a frequent intermediary in these modulatory effects. This conclusion, namely, that ion channel proteins are indeed substrates for phosphorylation, has been verified in numerous biochemical studies [reviewed in 1–6].The functional correlates of channel phosphorylation are known to involve a change in channel open probability and, in the case of voltage-sensitive ion channels, a shift in the voltage dependence of channel activation. The voltage dependence of ion channel gating appears to be governed by movement of charge in the voltage-sensing moiety. Analogous to alterations in enzyme activities following biochemical modification, phosphorylation of ion channel proteins may lead to conformational changes that subsequently alter their gating and/or conductive properties, giving rise to the observed changes in electrical activity. However, in many cases, it is not yet clear whether it is the ion channels themselves that are directly modified, or whether phosphorylation is simply an early step in a cascade of events that leads ultimately to modulation of channel activity. The development and application of single-channel recording techniques in membrane patches and in artificial planar lipid bilayers has provided a means to investigate the effects of phosphorylation on the kinetic properties of ion channels. Moreover, the recent application of site directed mutagenesis to cloned ion channels has pinpointed specific amino acid residues critical for the specific kinase effects

Centrifuge Modelling With Transparent Soil and Laser Aided Imaging

Transparent synthetic soils have been developed as a soil surrogate to enable internal visualization of geotechnical processes in physical models. While significant developments have been made to enhance the methodology and capabilities of transparent soil modelling, the technique is not yet exploited to its fullest potential. Tests are typically conducted at 1 g in small bench size models, which invokes concerns about the impact of scale and stress level observed in previously reported work. This paper recognized this limitation and outlines the development of improved testing methodology whereby the transparent soil and laser aided imaging technique are translated to the centrifuge environment. This has a considerable benefit such that increased stresses are provided, which better reflect the prototype condition. The paper describes the technical challenges associated with implementing this revised experimental methodology, summarizes the test equipment/systems developed, and presents initial experimental results to validate and confirm the successful implementation and scaling of transparent soil testing to the high gravity centrifuge test environment. A 0.6 m wide prototype strip foundation was tested at two scales using the principle of “modelling of models,” in which similar performance was observed. The scientific developments discussed have the potential to provide a step change in transparent soil modelling methodology, crucially providing more representative stress conditions that reflect prototype conditions, while making a broader positive contribution to physical modelling capabilities to assess complex soil–structure boundary problems

Quantification of Optical Clarity of Transparent Soil Using the Modulation Transfer Function

Transparent synthetic soils have been developed as a soil surrogate to enable internal visualization of geotechnical processes in physical models. Transparency of the soil dictates the overarching success of the technique; however, despite this fundamental requirement, no quantitative framework has yet been established to appraise the visual quality of transparent soil. Previous approaches to assess and optimize transparency quality included an eye chart assessment method, although this approach is highly subjective and operator-dependent. In this paper, an independent method for quantitatively assessing the optical quality of transparent soil is proposed based on the optical calibration method, Modulation Transfer Function (MTF). The work explores this hypothesis and assesses the potential for MTF to quantify the optical quality of transparent soils for a number of aspects including (i) optimum oil blend ratio, (ii) depth of viewing plane, and (iii) temperature. The results confirmed that MTF offers a robust and reliable method to provide an independent quantitative measure of the optical quality of transparent soil. The impact of reduced soil transparency and the ability to track speckle patterns—thus accuracy and precision of displacement measurement—was correlated with MTF to evaluate the permissible viewing depth of transparent soil

Many worlds and modality in the interpretation of quantum mechanics: an algebraic approach

Many worlds interpretations (MWI) of quantum mechanics avoid the measurement problem by considering every term in the quantum superposition as actual. A seemingly opposed solution is proposed by modal interpretations (MI) which state that quantum mechanics does not provide an account of what `actually is the case', but rather deals with what `might be the case', i.e. with possibilities. In this paper we provide an algebraic framework which allows us to analyze in depth the modal aspects of MWI. Within our general formal scheme we also provide a formal comparison between MWI and MI, in particular, we provide a formal understanding of why --even though both interpretations share the same formal structure-- MI fall pray of Kochen-Specker (KS) type contradictions while MWI escape them.Comment: submitted to the Journal of Mathematical Physic

A sudden presentation of abdominal compartment syndrome

Dear Editor, Abdominal compartment syndrome (ACS) is defined as sustained intra-abdominal pressure (IAP) exceeding 20 mm Hg, which causes end-organ damage due to impaired tissue perfusion, as with other compartment syndromes [1, 2]. This dysfunction can extend beyond the abdomen to other organs like the heart and lungs. ACS is most commonly caused by trauma or surgery to the abdomen. It is characterised by interstitial oedema, which can be exacerbated by large fluid shifts during massive transfusion of blood products and other fluid resuscitation [3]. Normally, IAP is nearly equal to or slightly above ambient pressure. Intra-abdominal hypertension is typically defined as abdominal pressure greater than or equal to 12 mm Hg [4]. Initially, the abdomen is able to distend to accommodate the increase in pressure caused by oedema; however, IAP becomes highly sensitive to any additional volume once maximum distension is reached. This is a function of abdominal compliance, which plays a key role in the development and progression of intra-abdominal hypertension [5]. Surgical decompression is required in severe cases of organ dysfunction – usually when IAPs are refractory to other treatment options [6]. Excessive abdominal pressure leads to systemic pathophysiological consequences that may warrant admission to a critical care unit. These include hypoventilation secondary to restriction of the deflection of the diaphragm, which results in reduced chest wall compliance. This is accompanied by hypoxaemia, which is exacerbated by a decrease in venous return. Combined, these consequences lead to decreased cardiac output, a V/Q mismatch, and compromised perfusion to intra-abdominal organs, most notably the kidneys [7]. Kidney damage can be prerenal due to renal vein or artery compression, or intrarenal due to glomerular compression [8] – both share decreased urine output as a manifestation. Elevated bladder pressure is also seen from compression due to increased abdominal pressure, and its measurement, via a Foley catheter, is a diagnostic hallmark. Sustained intra-bladder pressures beyond 20 mm Hg with organ dysfunction are indicative of ACS requiring inter­vention [2, 8]. ACS is an important aetiology to consider in the differential diagnosis for signs of organ dysfunction – especially in the perioperative setting – as highlighted in the case below

Potential of new isolates of Dunaliella Salina for natural β-Carotene production

The halotolerant microalga Dunaliella salina has been widely studied for natural β-carotene production. This work shows biochemical characterization of three newly isolated Dunaliella salina strains, DF15, DF17, and DF40, compared with D. salina CCAP 19/30 and D. salina UTEX 2538 (also known as D. bardawil). Although all three new strains have been genetically characterized as Dunaliella salina strains, their ability to accumulate carotenoids and their capacity for photoprotection against high light stress are different. DF15 and UTEX 2538 reveal great potential for producing a large amount of β-carotene and maintained a high rate of photosynthesis under light of high intensity; however, DF17, DF40, and CCAP 19/30 showed increasing photoinhibition with increasing light intensity, and reduced contents of carotenoids, in particular β-carotene, suggesting that the capacity of photoprotection is dependent on the cellular content of carotenoids, in particular β-carotene. Strong positive correlations were found between the cellular content of all-trans β-carotene, 9-cis β-carotene, all-trans α-carotene and zeaxanthin but not lutein in the D. salina strains. Lutein was strongly correlated with respiration in photosynthetic cells and strongly related to photosynthesis, chlorophyll and respiration, suggesting an important and not hitherto identified role for lutein in coordinated control of the cellular functions of photosynthesis and respiration in response to changes in light conditions, which is broadly conserved in Dunaliella strains. Statistical analysis based on biochemical data revealed a different grouping strategy from the genetic classification of the strains. The significance of these data for strain selection for commercial carotenoid production is discussed

Anterior eye surface changes following miniscleral contact lens wear

Purpose To quantify the effect of short-term miniscleral contact lens wear on the anterior eye surface of healthy eyes, including cornea, corneo-scleral junction and sclero-conjuctival area. Methods Twelve healthy subjects (29.9 ± 5.7 years) wore a highly gas-permeable miniscleral contact lens of 16.5 mm diameter during a 5-hour period. Corneo-scleral height profilometry was captured before, immediately following lens removal and 3 h after lens removal. Topography based corneo-scleral limbal radius estimates were derived from height measurements. In addition, elevation differences in corneal and scleral region were calculated with custom-written software. Sclero-conjuctival flattening within different sectors was analysed. Results Short-term miniscleral lens wear significantly modifies the anterior eye surface. Significant limbal radius increment (mean ± standard deviation) of 146 ± 80 μm, (p = 0.004) and flattening of −122 ± 90 μm in the sclero-conjuctival area, (p << 0.001) were observed immediately following lens removal. These changes did not recede to baseline levels 3 h after lens removal. The greatest anterior eye surface flattening was observed in the superior sector. No statistically significant corneal shape change was observed immediately following lens removal or during the recovery period. Conclusions Short-term miniscleral contact lens wear in healthy eyes does not produce significant corneal shape changes measured with profilometry but alters sclero-conjuctival topography. In addition, sclero-conjuctival flattening was not uniformly distributed across the anterior eye

CDC Grand Rounds: National Amyotrophic Lateral Sclerosis (ALS) Registry Impact, Challenges, and Future Directions

Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig’s disease, is a rapidly progressive fatal neurologic disease. Currently, there is no cure for ALS and the available treatments only extend life by an average of a few months. The majority of ALS patients die within 2–5 years of diagnosis, though survival time varies depending on disease progression (1,2). For approximately 10% of patients, ALS is familial, meaning it and has a genetic component; the remaining 90% have sporadic ALS, where etiology is unknown, but might be linked to environmental factors such as chemical exposures (e.g., heavy metals, pesticides) and occupational history (3). Like many other noncommunicable conditions, ALS is a nonnotifiable disease in the United States; therefore, the federal government lacks reliable incidence and prevalence estimates for the United States. During October 2008, Congress passed the ALS Registry Act (4), directing CDC and its sister agency, the Agency for Toxic Substances and Disease Registry, to create a population-based ALS registry for the United States. The main objectives of the National ALS Registry, which was launched in October 2010, are to describe the national incidence and prevalence of ALS; describe the demographics of persons living with ALS; and examine risk factors for the disease (4,5). During January 2017, the Registry launched the National ALS Biorepository, which aims to promote research in areas including biomarkers, genetics, and environmental exposures to heavy metals or organophosphates (6,7)

Utility of human life cost in anaesthesiology cost-benefit decisions

The United States (US) aviation industry provides a potentially useful mental model for dealing with certain cost-benefit decisions in aesthesiology. The Federal Aviation Administration (FAA), the national aviation authority of the United States, quantifies a price for the value of a human life based on the U.S. Department of Transportation’s (DOT) value of a statistical life (VSL) unit. The current VSL is around $9.6 million, indexed to grow with consideration given to inflation and wage changes from the 2016 baseline of$9.4 million [1]. To illustrate the concept, if the FAA estimates that 100 people are likely to die in the future given the current practice standards then the monetary cost of this loss will be $940 million. The FAA uses this estimated monetary value as an official reference point in its regulatory decisions, and the agency publishes in detail how it derives the estimated value. When proposing new regulations, the FAA bases its decisions on comparisons of the human life cost associated with the existing regulation versus the alternative cost that the industry stakeholders will incur subsequent to the adoption of the regulation. In this example, if the cost incurred by the industry is more than the$940 million cost then the FAA will not adopt the proposed regulation and hence will not require the industry to undertake this cost

The influence of delayed light curing on the degree of conversion and polymerization contraction stress in dual-cured resin luting agents

The aim of the study was to assess the effect of delayed photo-initiation on the polymerization contraction stress (PCS) and degree of conversion (DC) of a dual-cure resin-luting agent. Thirty-five disk (6 mm × 1 mm) samples (n = 10 each group) of dual cure resin luting agent for PCS assessment were fabricated and polymerized using two illuminated quartz rods. Based on the delay in photo-initiation, 30 disks were divided among six groups [group A-0 min (min) delay, group B-2 min, group C-4 min, group D-6 min, group E-8 min and group F-10 min]. A non-photoinitiated group (group G – chemical cure – n = 5) was included as control. The PCS for all specimens was assessed using a Tensometer. For DC evaluation thirty-five specimens were divided into seven groups with delays in photo-initiation (group H-0 min, group I-2 min, group J-4 min, group K-6 min, group L-8 min and group M-10 min, group N-chemical cure). DC was assessed using attenuated total reflectance spectroscopic technique. Statistical comparison among groups was performed using analysis of variance (α = 0.05). The maximum and minimum PCS and DC values with delayed photo-initiation was observed in group-C (3.34 MPa) & group-F (2.44 MPa); and group-M (0.78 MPa) and group-H (0.55 MPa) respectively. Chemically cured samples showed the least PCS (group-G, 1.94) and DC (group-N, 0.53) values in their respective categories. PCS significantly decreased with delayed photo-initiation. A significant increase in DC was noticed when photo-initiation was delayed in the dual cure resin luting agent