Herding in Quality Assessment: An Application to Organ Transplantation

There are many economic environments in which an object is offered sequentially to prospective buyers. It is often observed that once the object for sale is turned down by one or more agents, those that follow do the same. One explanation that has been p

Biomimetic heterogenous elastic tissue development

There is an unmet need for artificial tissue to address current limitations with donor organs and problems with donor site morbidity. Despite the success with sophisticated tissue engineering endeavours, which employ cells as building blocks, they are limited to dedicated labs suitable for cell culture, with associated high costs and long tissue maturation times before available for clinical use. Direct 3D printing presents rapid, bespoke, acellular solutions for skull and bone repair or replacement, and can potentially address the need for elastic tissue, which is a major constituent of smooth muscle, cartilage, ligaments and connective tissue that support organs. Thermoplastic polyurethanes are one of the most versatile elastomeric polymers. Their segmented block copolymeric nature, comprising of hard and soft segments allows for an almost limitless potential to control physical properties and mechanical behaviour. Here we show direct 3D printing of biocompatible thermoplastic polyurethanes with Fused Deposition Modelling, with a view to presenting cell independent in-situ tissue substitutes. This method can expeditiously and economically produce heterogenous, biomimetic elastic tissue substitutes with controlled porosity to potentially facilitate vascularisation. The flexibility of this application is shown here with tubular constructs as exemplars. We demonstrate how these 3D printed constructs can be post-processed to incorporate bioactive molecules. This efficacious strategy, when combined with the privileges of digital healthcare, can be used to produce bespoke elastic tissue substitutes in-situ, independent of extensive cell culture and may be developed as a point-of-care therapy approach

The occupancy of two distinct conformations by active-site histidine-119 in crystals of ribonuclease is modulated by pH

AbstractStructures of a semisynthetic RNase have been obtained to a resolution of 2.0 Å at pH values of 5.2, 6.5, 7.5, and 8.8, respectively. The principle structural transformation occurring over this pH range is the conversion of the side chain of active site residue His-119 from one conformation (X1 = −43° to −57°) at low pH to another (X1 = + 159° to + 168°) at higher pH values. On the basis of this observation, a model is proposed that reconciles the disparate pK values for His-119 in the enzyme-substrate complex that have been deduced from kinetic studies and from proton NMR measurements in the presence of pseudosubstrates

Structural changes that accompany the reduced catalytic efficiency of two semisynthetic ribonuclease analogs

The structures of two catalytically defective semi-synthetic RNases obtained by replacing aspartic acid 121 with asparagine or alanine have been determined and refined at a resolution of 2.0 A (R = 0.186 and 0.172, respectively). When these structures are compared with the refined 1.8-A structure (R = 0.204) of the fully active aspartic acid-containing enzyme (Martin, P.D., Doscher, M.S., and Edwards, B. F. P. (1987) J. Biol. Chem. 262, 15930-15938), numerous and widespread changes, much greater in number and magnitude than the small structural variations noted previously between the semisynthetic complex and RNase A, are found to have occurred. These changes include the movement of the loop containing residues 65-72 away from the active site, a more or less generalized relocation of crystallographically bound water molecules, and a number of rearrangements in the hydrogen bonding network at the active site. Most changes are far removed from the immediate site of the modifications and are distributed essentially throughout the molecule. The details of many of these changes are unique to each analog. In the asparagine analog, a destabilization in the positioning of active site residue His-119 also appears to have occurred

Partial observable update for subjective logic and its application for trust estimation

Subjective Logic (SL) is a type of probabilistic logic, which is suitable for reasoning about situations with uncertainty and incomplete knowledge. In recent years, SL has drawn a significant amount of attention from the multi-agent systems community as it connects beliefs and uncertainty in propositions to a rigorous statistical characterization via Dirichlet distributions. However, one serious limitation of SL is that the belief updates are done only based on completely observable evidence. This work extends SL to incorporate belief updates from partially observable evidence. Normally, the belief updates in SL presume that the current evidence for a proposition points to only one of its mutually exclusive attribute states. Instead, this work considers that the current attribute state may not be completely observable, and instead, one is only able to obtain a measurement that is statistically related to this state. In other words, the SL belief is updated based upon the likelihood that one of the attributes was observed. The paper then illustrates properties of the partial observable updates as a function of the state likelihood and illustrates the use of these likelihoods for a trust estimation application. Finally, the utility of the partial observable updates is demonstrated via various simulations including the trust estimation case.U.S. Army Research Laboratory ; U.K. Ministry of Defence ; TÜBİTAKpre-prin

Compensated right ventricular function of the onset of pulmonary hypertension in a rat model depends on chamber remodeling and contractile augmentation.

Right-ventricular function is a good indicator of pulmonary arterial hypertension (PAH) prognosis; however, how the right ventricle (RV) adapts to the pressure overload is not well understood. Here, we aimed at characterizing the time course of RV early remodeling and discriminate the contribution of ventricular geometric remodeling and intrinsic changes in myocardial mechanical properties in a monocrotaline (MCT) animal model. In a longitudinal study of PAH, ventricular morphology and function were assessed weekly during the first four weeks after MCT exposure. Using invasive measurements of RV pressure and volume, heart performance was evaluated at end of systole and diastole to quantify contractility (end-systolic elastance) and chamber stiffness (end-diastolic elastance). To distinguish between morphological and intrinsic mechanisms, a computational model of the RV was developed and used to determine the level of prediction when accounting for wall masses and unloaded volume measurements changes. By four weeks, mean pulmonary arterial pressure and elastance rose significantly. RV pressures rose significantly after the second week accompanied by significant RV hypertrophy, but RV stroke volume and cardiac output were maintained. The model analysis suggested that, after two weeks, this compensation was only possible due to a significant increase in the intrinsic inotropy of RV myocardium. We conclude that this MCT-PAH rat is a model of RV compensation during the first month after treatment, where geometric remodeling on EDPVR and increased myocardial contractility on ESPVR are the major mechanisms by which stroke volume is preserved in the setting of elevated pulmonary arterial pressure. The mediators of this compensation might themselves promote longer-term adverse remodeling and decompensation in this animal model

Taxing the Informal Economy: The Current State of Knowledge and Agendas for Future Research

This paper reviews the literature on taxation of the informal economy, taking stock of key debates and drawing attention to recent innovations. Conventionally, the debate on whether to tax has frequently focused on the limited revenue potential, high cost of collection, and potentially adverse impact on small firms. Recent arguments have increasingly emphasised the more indirect benefits of informal taxation in relation to economic growth, broader tax compliance, and governance. More research is needed, we argue, into the relevant costs and benefits for all, including quasi-voluntary compliance, political and administrative incentives for reform, and citizen-state bargaining over taxation