Molecular analysis of the functional role of beta-adrenergic receptor kinase 1 amino-terminal

Receptor phosphorylation is a key step in the process of rapid desensitization. beta-adrenergic receptor kinase (betaARK) is a specific receptor kinase that is known to phosphorylate and induce desensitization of several G-coupled receptors only when they are occupied by their agonists. In the present study we have done several modifications to the amino-terminal of betaARK1, in order to clarify its functional role. The recombinant mutants were tested for their ability to phosphorylate rhodopsin present in purified bovine ROS membranes which serves as a substrate for betaARK1. Their expression levels were detected by Western blot analysis. We found that when the amino-terminal of betaARK1 is modified its expression level is very low, hence it is not able to phosphorylate over the basal. These findings suggest that this region is crucial for the normal processing of the protein.     

Strategic decision making on complex systems

In this paper, we propose a challenging research direction for Constraint Programming and optimization techniques in general. We address problems where decisions to be taken affect and are affected by complex systems, which exhibit phenomena emerging from a collection of interacting objects, capable to self organize and to adapt their behaviour according to their history and feedback. Such systems are unfortunately impervious to modeling efforts via state-of-the-art combinatorial optimization techniques. We provide some hints on approaches to connect and integrate decision making and optimization technology with complex systems via machine learning, game theory and mechanism design. In the first case, the aim is to extract modeling components to express the relation between global decisions and observables emerging from the real system, or from an accurate predictive model (e.g. a simulator). In the second case, the idea is to exploit game theory, mechanism design and distributed decision making to drive the process toward realistic equilibrium points avoiding globally optimal, but unrealistic, configurations. We conclude by observing how dealing with the complexity of the considered problems will require to greatly extend the capabilities of state of the art solvers: in this context, we identify some key issues and highlight future research directions.     

DANCo: An intrinsic dimensionality estimator exploiting angle and norm concentration

In the past decade the development of automatic intrinsic dimensionality estimators has gained considerable attention due to its relevance in several application fields. However, most of the proposed solutions prove to be not robust on noisy datasets, and provide unreliable results when the intrinsic dimensionality of the input dataset is high and the manifold where the points are assumed to lie is nonlinearly embedded in a higher dimensional space. In this paper we propose a novel intrinsic dimensionality estimator (DANCo) and its faster variant (FastDANCo), which exploit the information conveyed both by the normalized nearest neighbor distances and by the angles computed on couples of neighboring points. The effectiveness and robustness of the proposed algorithms are assessed by experiments on synthetic and real datasets, by the comparative evaluation with state-of-the-art methodologies, and by significance tests.     

Two-phase pressure drops in a helically coiled steam generator

An experimental investigation regarding two-phase diabatic pressure drops inside a helically coiled heat exchanger have been carried out at SIET thermo-hydraulics labs in Piacenza (Italy). The experimental campaign is part of a wide program of study of the IRIS innovative reactor steam generator. The test section consists of an AISI 316 stainless steel tube, 32 m length, 12.53 mm inner diameter, curved in helical shape with a bend radius of 0.5 m and a helix pitch of 0.8 m, resulting in a total height of the steam generator tube of 8 m. The explored operating conditions for two-phase flow experiences range from 192 to 824 kg/m² s for the mass flux, from 0 to 1 for the quality, from 1.1 to 6.3 MPa for the pressure, from 50 to 200 kW/m² for the heat fluxes. A frictional two-phase pressure drops correlation, based on an energy balance of the two-phase mixture and including the 940 experimental points, is proposed. Comparison with existing correlations shows the difficulty in predicting two-phase pressure drops in helical coil steam generators.     

Factors influencing worker use of personal protective eyewear

Objective

To identify and describe the array of factors that influence a workers’ decision to wear personal protective eyewear (PPE) and the barriers that exist in preventing their use.

Design, setting and participants

A series of focus groups enrolled workers and supervisors primarily from manufacturing, construction, or service/retail industries that had potential exposure to eye injury hazards in their job tasks. Focus group sessions were facilitated to collect qualitative and quantitative data in two categories, “sought information” and “emergent themes”, related to the factors influencing use of PPE.

Results

We conducted a series of 7 groups with 51 participants, 36 (71%) males and 15 (29%) females ranging in age from 19 to 64 years old, from a variety of occupations including construction (24%), production (22%), installation, repair and maintenance (14%), and healthcare (10%). Most were highly experienced in their occupation (>10 years); males (86%) and females (53%), and had received some safety training in the past (82%). The majority of workers in this study were required to wear PPE on their worksite (78%), however only 55% had a dedicated safety officer. A conceptual model that summarizes the “sought information” and “emergent themes” is presented that depicts the decision making process for the factors influencing use of PPE and consists of three primary branches; perceptions of hazards and risks, “barriers” to PPE usage, and enforcement and reinforcement. Lack of comfort/fit, and fogging and scratching of the eyewear were suggested as the most important barriers to PPE usage. Younger age and lack of safety training were other important factors affecting use of PPE.

Conclusions

Several potentially modifiable factors identified would lead to an increase in workers’ PPE use and encourage supervisors to provide ongoing positive feedback on the continuous use of PPE by workers at risk for an eye injury.     

A Markov model for the mobile propagation channel

A finite-state Markov model is fitted to the mobile propagation channel by the use of contingency tables. Narrow-band Rayleigh and Ricean fading are considered in detail, but the techniques extend to other types of fading. Several criteria may indicate that a first-order finite-state Markov model sufficiently characterizes the channel behavior. The parameters of the model are obtained both from theoretical analysis and simulation. Functional dependence between the transition probabilities and the steady-state probabilities is found in the slow fading case     

MAFLD and CKD: An Updated Narrative Review

Accumulating evidence now indicates that non-alcoholic fatty liver disease (NAFLD), which is the most common chronic liver disease observed in clinical practice worldwide, is independently associated with an increased risk of incident chronic kidney disease (CKD). Given that NAFLD is linked to insulin resistance, obesity and type 2 diabetes mellitus, an international panel of experts have recently proposed a name change from NAFLD to metabolic associated fatty liver disease (MAFLD). Since the diagnostic criteria for NAFLD and MAFLD are different, observational studies assessing the potential concordance (or even superiority) of MAFLD, compared with NAFLD, in detecting patients at increased risk of hepatic and extra-hepatic complications (including CKD) are required. Hence, in the last two years, some observational studies have investigated the potential relationship between MAFLD and CKD. The result is that, at present, evidence regarding the concordance or even superiority of MAFLD, compared with NAFLD, in detecting patients at higher risk of CKD is still preliminary, although some data indicate that MAFLD identifies patients with CKD as accurately as NAFLD. In this narrative review, we will discuss: (a) the epidemiological evidence assessing the association between NAFLD and risk of incident CKD, (b) the epidemiological data investigating the association between MAFLD and risk of CKD and (c) the biological mechanisms underlying the association between NAFLD/MAFLD and CKD.     

Isolation,Identification, and Characterisation of Beer‐Spoilage Lactic Acid Bacteria from Microbrewed Beer from Victoria,Australia

Lactic acid bacteria are the most frequently encountered beer‐spoilage bacteria, and they may render beer undrinkable due to the production of lactic acid, diacetyl, and turbidity. Microbrewed beer is typically sold unpasteurised, leaving it more susceptible to spoilage by lactic acid bacteria. In this study, the incidence of lactic acid bacteria in bottled microbrewed beer from Victoria, Australia was investigated. A total of 80 beers from 19 breweries were screened for lactic acid bacteria. Almost 30% contained culturable lactic acid bacteria, and many had lactic acid levels well above the flavour threshold. Ethanol, hops, and the pH levels of the beers were not predictors for spoilage in the beers examined, and contamination appeared to be more closely linked to the source brewery. The 45 lactic acid strains isolated from these beers were identified by RAPD‐PCR, with Lactobacillus brevis being the most frequently isolated species. All isolates were capable of spoiling beer and contained putative hop resistance genes. At typical beer levels, pH and ethanol had no effect on the growth of the particular spoilage bacteria isolated in this study.     

AcidoCEST-UTE MRI Reveals an Acidic Microenvironment in Knee Osteoarthritis

A relationship between an acidic pH in the joints, osteoarthritis (OA), and pain has been previously demonstrated. Acidosis Chemical Exchange Saturation Transfer (acidoCEST) indirectly measures the extracellular pH through the assessment of the exchange of protons between amide groups on iodinated contrast agents and bulk water. It is possible to estimate the extracellular pH in the osteoarthritic joint using acidoCEST MRI. However, conventional MR sequences cannot image deep layers of cartilage, meniscus, ligaments, and other musculoskeletal tissues that present with short echo time and fast signal decay. Ultrashort echo time (UTE) MRI, on the other hand, has been used successfully to image those joint tissues. Here, our goal is to compare the pH measured in the knee joints of volunteers without OA and patients with severe OA using acidoCEST-UTE MRI. Patients without knee OA and patients with severe OA were examined using acidoCEST-UTE MRI and the mean pH of cartilage, meniscus, and fluid was calculated. Additionally, the relationship between the pH measurements and the Knee Injury and Osteoarthritis Outcome Score (KOOS) was investigated. AcidoCEST-UTE MRI can detect significant differences in the pH of knee cartilage, meniscus, and fluid between joints without and with OA, with OA showing lower pH values. In addition, symptoms and knee-joint function become worse at lower pH measurements.