Is Osteogenic Differentiation of Human Nucleus Pulposus Cells a Possibility for Biological Spinal Fusion?

Objective The purpose of this study was to investigate whether a simple, biologically robust method for inducing calcification of degenerate intervertebral discs (IVD) could be developed to provide an alternative treatment for patients requiring spinal fusion. Design Nucleus pulposus (NP) cells isolated from 14 human IVDs were cultured in monolayer and exposed to osteogenic medium, 1,25-dihydroxyvitamin D3 (VitD3), parathyroid hormone (PTH), and bone morphogenic proteins (BMPs) 2/7 to determine if they could become osteogenic. Similarly explant cultures of IVDs from 11 patients were cultured in osteogenic media with and without prior exposure to VitD3 and BMP-2. Osteogenic differentiation was assessed by alkaline phosphatase activity and areas of calcification identified by alizarin red or von Kossa staining. Expression of osteogenic genes during monolayer culture was determined using polymerase chain reaction and explant tissues assessed for BMP inhibitors. Human bone marrow-derived mesenchymal stromal cells (MSCs) were used for comparison. Results Standard osteogenic media was optimum for promoting mineralization by human NP cells in monolayer. Some osteogenic differentiation was observed with 10 nM VitD3, but none following application of PTH or BMPs. Regions of calcification were detected in 2 of the eleven IVD tissue explants, one cultured in osteogenic media and one with the addition of VitD3 and BMP-2. Conclusions Human NP cells can become osteogenic in monolayer and calcification of the extracellular matrix can also occur, although not consistently. Inhibitory factors within either the cells or the extracellular matrix may hinder osteogenesis, indicating that a robust biological fusion at this time requires further optimization

Consequences of selecting technology pathways on cumulative carbon dioxide emissions for the United Kingdom

The UK has an ambitious target of an 80% reduction in carbon dioxide emissions by 2050, to be reached using a series of ‘carbon budgets’ to aid policy development. Current energy systems modelling methods do not explore, or are unable to account for, physical (thermodynamic) limits to the rate of change of infrastructure. The power generation sector has a variety of technological options for this low-carbon transition. We compare physically constrained scenarios that accentuate either carbon capture and storage, fastest plausible nuclear new build, or fastest plausible build rate of offshore wind. We set these in the context of the UK’s legislated fifth carbon budget, which has a comprehensive range of carbon reduction measures with respect to business-as-usual. The framework for our scenario comparison uses our novel system dynamics model to substantiate the policy’s ability to meet 2035 emissions targets while maintaining financial productivity and socially expected employment levels. For an ambitious nuclear new build programme we find that even if it stays on track it is more expensive than offshore wind generation and delays emissions reductions. This affects the cumulative emissions and impacts on the UK’s ability to contribute to international climate change targets. If delays or cancellation occur to the deployment programmes of carbon capture and storage technologies or nuclear new build, we suggest the electricity and decarbonisation targets can by met by a fast growth of offshore wind generation with no change to financial and employment levels.Arup’s internal Design and Technical Fun

Modelling socio-economic and energy data to generate business-as-usual scenarios for carbon emissions

The UK Government is legally committed to achieving an 80% reduction in carbon dioxide emissions compared with 1990 by 2050. The use of scenarios is wide ranging to inform policy development and forming a businessas-usual scenario helps to understand possible effects of different policy interventions. However, the term business-as-usual is frequently misused. We show how econo-physical business-as-usual scenarios can be developed by examining the historical behaviour of coefficients which manifest the relationship between components of an economy. We endogenise economic growth by mimicking national level policies that focus on a target level of unemployment. Our case-study demonstrates the ‘trendability’ of coefficients which for one example coefficient is replicated for Australia, Colombia, Taiwan and the USA. We manifest a gross domestic product growth of 2% falling to 1% which contrasts with an exogenous growth of 2.3% of a comparator business-as-usual scenario. We suggest that it may be possible to achieve a greater reduction in the business-asusual carbon dioxide emissions in the UK fifth carbon budget than currently projected.Arup’s internal Design and Technical Fun

Thermomechanical modelling of laser surface glazing for H13 tool steel

A two-dimensional thermomechanical finite element (FE) model of laser surface glazing (LSG) has been developed for H13 tool steel. The direct coupling technique of ANSYS 17.2 (APDL) has been utilised to solve the transient thermomechanical process. A H13 tool steel cylindrical cross-section has been modelled for laser power 200 W and 300 W at constant 0.2 mm beam width and 0.15 ms residence time. The model can predict temperature distribution, stress–strain increments in elastic and plastic region with time and space. The crack formation tendency also can be assumed by analysing the von Mises stress in the heat-concentrated zone. Isotropic and kinematic hardening models have been applied separately to predict the after-yield phenomena. At 200 W laser power, the peak surface temperature achieved is 1520 K which is below the melting point (1727 K) of H13 tool steel. For laser power 300 W, the peak surface temperature is 2523 K. Tensile residual stresses on surface have been found after cooling, which are in agreement with literature. Isotropic model shows higher residual stress that increases with laser power. Conversely, kinematic model gives lower residual stress which decreases with laser power. Therefore, both plasticity models could work in LSG for H13 tool steel

A 3-player protocol preventing persistence in strategic contention with limited feedback

In this paper, we study contention resolution protocols from a game-theoretic perspective. In a recent work, we considered acknowledgment-based protocols, where a user gets feedback from the channel only when she attempts transmission. In this case she will learn whether her transmission was successful or not. One of the main results of ESA2016 was that no acknowledgment-based protocol can be in equilibrium. In fact, it seems that many natural acknowledgment-based protocols fail to prevent users from unilaterally switching to persistent protocols that always transmit with probability 1. It is therefore natural to ask how powerful a protocol must be so that it can beat persistent deviators. In this paper we consider age-based protocols, which can be described by a sequence of probabilities of transmitting in each time step. Those probabilities are given beforehand and do not change based on the transmission history. We present a 3-player age-based protocol that can prevent users from unilaterally deviating to a persistent protocol in order to decrease their expected transmission time. It is worth noting that the answer to this question does not follow from the results and proof ideas of ESA2016. Our protocol is non-trivial, in the sense that, when all players use it, finite expected transmission time is guaranteed. In fact, we show that this protocol is preferable to any deadline protocol in which, after some fixed time, attempt transmission with probability 1 in every subsequent step. An advantage of our protocol is that it is very simple to describe, and users only need a counter to keep track of time. Whether there exist $n$-player age-based protocols that do not use counters and can prevent persistence is left as an open problem for future research.Comment: arXiv admin note: substantial text overlap with arXiv:1606.0658

Human skeletal muscle plasmalemma alters its structure to change its Ca2+-handling following heavy-load resistance exercise

High-force eccentric exercise results in sustained increases in cytoplasmic Ca2+ levels ([Ca2+]cyto), which can cause damage to the muscle. Here we report that a heavy-load strength training bout greatly alters the structure of the membrane network inside the fibres, the tubular (t-) system, causing the loss of its predominantly transverse organization and an increase in vacuolation of its longitudinal tubules across adjacent sarcomeres. The transverse tubules and vacuoles displayed distinct Ca2+-handling properties. Both t-system components could take up Ca2+ from the cytoplasm but only transverse tubules supported store-operated Ca2+ entry. The retention of significant amounts of Ca2+ within vacuoles provides an effective mechanism to reduce the total content of Ca2+ within the fibre cytoplasm. We propose this ability can reduce or limit resistance exercise-induced, Ca2+-dependent damage to the fibre by the reduction of [Ca2+]cyto to help maintain fibre viability during the period associated with delayed onset muscle soreness

Rapid Effects of Marine Reserves via Larval Dispersal

Marine reserves have been advocated worldwide as conservation and fishery management tools. It is argued that they can protect ecosystems and also benefit fisheries via density-dependent spillover of adults and enhanced larval dispersal into fishing areas. However, while evidence has shown that marine reserves can meet conservation targets, their effects on fisheries are less understood. In particular, the basic question of if and over what temporal and spatial scales reserves can benefit fished populations via larval dispersal remains unanswered. We tested predictions of a larval transport model for a marine reserve network in the Gulf of California, Mexico, via field oceanography and repeated density counts of recently settled juvenile commercial mollusks before and after reserve establishment. We show that local retention of larvae within a reserve network can take place with enhanced, but spatially-explicit, recruitment to local fisheries. Enhancement occurred rapidly (2 yrs), with up to a three-fold increase in density of juveniles found in fished areas at the downstream edge of the reserve network, but other fishing areas within the network were unaffected. These findings were consistent with our model predictions. Our findings underscore the potential benefits of protecting larval sources and show that enhancement in recruitment can be manifested rapidly. However, benefits can be markedly variable within a local seascape. Hence, effects of marine reserve networks, positive or negative, may be overlooked when only focusing on overall responses and not considering finer spatially-explicit responses within a reserve network and its adjacent fishing grounds. Our results therefore call for future research on marine reserves that addresses this variability in order to help frame appropriate scenarios for the spatial management scales of interest

A novel observation of pubic osteomyelitis due to Streptococcus viridans after dental extraction: a case report

<p>Abstract</p> <p>Introduction</p> <p>Pubic osteomyelitis should be suspected in athletic individuals with sudden groin pain, painful restriction of hip movements and fever. It is an infrequent and confusing disorder, which is often heralded by atypical gait disturbance and diffuse pain in the pelvic girdle. The most common pathogen is <it>Staphylococcus aureus </it>but, on occasions, efforts to identify infectious agents sometimes prove negative. Pubic osteomyelitis due to <it>Streptococcus viridans </it>has not been reported previously in the literature.</p> <p>Case presentation</p> <p>We describe the case of a fit 24-year-old athlete, who had a wisdom tooth extracted 2 weeks prior to the presentation, which could have served as a port of entry and predisposed the patient to transient bacteraemia.</p> <p>Conclusion</p> <p><it>S. viridans </it>is well known for causing infective endocarditis of native damaged heart valves, but to the best of the authors' knowledge it has not been reported previously as a cause of pubic osteomyelitis. We believe that this case should alert physicians to the association between dental procedures and osteomyelitis of the pubis secondary to <it>S. viridans</it>.</p

Selective vulnerability in α-synucleinopathies

Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy are neurodegenerative disorders resulting in progressive motor/cognitive deficits among other symptoms. They are characterised by stereotypical brain cell loss accompanied by the formation of proteinaceous aggregations of the protein α-synuclein (α-syn), being, therefore, termed α-synucleinopathies. Although the presence of α-syn inclusions is a common hallmark of these disorders, the exact nature of the deposited protein is specific to each disease. Different neuroanatomical regions and cellular populations manifest a differential vulnerability to the appearance of protein deposits, cell dysfunction, and cell death, leading to phenotypic diversity. The present review describes the multiple factors that contribute to the selective vulnerability in α-synucleinopathies. We explore the intrinsic cellular properties in the affected regions, including the physiological and pathophysiological roles of endogenous α-syn, the metabolic and genetic build-up of the cells and their connectivity. These factors converge with the variability of the α-syn conformational strains and their spreading capacity to dictate the phenotypic diversity and regional vulnerability of each disease. Finally, we describe the exogenous and environmental factors that potentially contribute by igniting and modulating the differential pathology in α-synucleinopathies. In conclusion, we think that it is the confluence of this disruption of the cellular metabolic state and α-syn structural equilibrium through the anatomical connectivity which appears to initiate cascades of pathological processes triggered by genetic, environmental, or stochastic events that result in the "death by a thousand cuts" profile of α-synucleinopathies

Can disordered mobile phone use be considered a behavioral addiction? An update on current evidence and a comprehensive model for future research

Despite the many positive outcomes, excessive mobile phone use is now often associated with potentially harmful and/or disturbing behaviors (e.g., symptoms of deregulated use, negative impact on various aspects of daily life such as relationship problems, and work intrusion). Problematic mobile phone use (PMPU) has generally been considered as a behavioral addiction that shares many features with more established drug addictions. In light of the most recent data, the current paper reviews the validity of the behavioral addiction model when applied to PMPU. On the whole, it is argued that the evidence supporting PMPU as an addictive behavior is scarce. In particular, it lacks studies that definitively show behavioral and neurobiological similarities between mobile phone addiction and other types of legitimate addictive behaviors. Given this context, an integrative pathway model is proposed that aims to provide a theoretical framework to guide future research in the field of PMPU. This model highlights that PMPU is a heterogeneous and multi-faceted condition