The role of Virus "X" (Tortoise Picornavirus) in kidney disease and shell weakness syndrome in European tortoise species determined by experimental infection

Tortoise Picornavirus (ToPV) commonly known as Virus "X" was recently discovered in juvenile European tortoises suffering from soft carapace and plastron as well as kidney disease. Therefore, this virus was a potential candidate to be a causative agent for these disease patterns. Spur thighed tortoises (Testudo graeca) seemed to be more susceptible to establish clinical symptoms than other European species like T. hermanni. Thus this trial investigated the role of ToPV in the described syndrome. Two groups of juvenile European tortoises (T. graeca and T.hermanni) each of 10 animals, were cloacally, oronasally and intracoelomically inoculated with an infectious dose (~ 2000 TICD) of a ToPV strain isolated from a diseased T. graeca. A control group of two animals of each species received non-infected cell culture supernatant. The tortoises were examined daily and pharyngeal and cloacal swabs for detection of ToPV-RNA by RT-PCR were taken from each animal every six days for a period of 6 months. At the end of the study the remaining animals were euthanised and dissected. Bacteriological and parasitological tests were performed and organ samples of all tortoises were investigated by RT-PCR for the presence of ToPV and histopathology. Animals that were euthanised at the end of the experiment, were examined for presence of specific anti-ToPV antibodies. Several animals in both inoculated groups showed retarded growth and a light shell weakness, in comparison to the control animals. Three animals were euthanised during the trial, showing reduced weight gain, retarded growth, severe shell weakness and apathy, in parallel to clinical observations in naturally infected animals. In all inoculated animals of both species an intermittent virus shedding, starting from 18 days post inoculation (d.p.i.), till 164 d.p.i. was detected, while the control animals remained negative. The virus was successfully reisolated in terrapene heart cell culture in 16 of 20 inoculated animals of both species. Histopathology of most inoculated animals revealed a lack of bone remodeling and vacuolisation in kidney tubuli which supports the described pathogenesis of nephropathy and osteodystrophy. Anti- ToPV antibody titres ranged from 1:2 to >1:256 in 13 of 20 animals, whereas all control animals were seronegative. The study proofed the Henle Koch`s postulates of ToPV as causative agent for shell dystrophy and kidney disease in both testudo species. The proposed species specific sensitivity towards clinical disease was not observed

Palaeobiology, ecology, and distribution of stromatoporoid faunas in biostromes of the mid-Ludlow of Gotland

Six well exposed mid−Ludlow stromatoporoid−dominated reef biostromes in four localities from the Hemse Group in southeastern Gotland, Sweden comprise a stromatoporoid assemblage dominated by four species; Clathrodictyon mohicanum, “Stromatopora” bekkeri, Plectostroma scaniense, and Lophiostroma schmidtii. All biostromes investigated in this area (of approximately 30 km2) are interpreted to belong to a single faunal assemblage forming a dense accumulation of fossils that is probably the best exposed stromatoporoid−rich deposit of the Silurian. The results from this comprehensive study strengthen earlier interpretations of a combination of genetic and environmental control on growth−forms of the stromatoporoids. Growth styles are similar for stromatoporoids in all six biostromes. Differences in biostrome fabric are due to variations in the degree of disturbance by storms. The uniformity of facies and the widespread low−diversity fauna support the view that palaeoenvironmental conditions were similar across the area where these biostromes crop out, and promoted the extraordinary growth of stromatoporoids in this shallow shelf area

Colorectal Cancer Through Simulation and Experiment

Colorectal cancer has continued to generate a huge amount of research interest over several decades, forming a canonical example of tumourigenesis since its use in Fearon and Vogelstein’s linear model of genetic mutation. Over time, the field has witnessed a transition from solely experimental work to the inclusion of mathematical biology and computer-based modelling. The fusion of these disciplines has the potential to provide valuable insights into oncologic processes, but also presents the challenge of uniting many diverse perspectives. Furthermore, the cancer cell phenotype defined by the ‘Hallmarks of Cancer’ has been extended in recent times and provides an excellent basis for future research. We present a timely summary of the literature relating to colorectal cancer, addressing the traditional experimental findings, summarising the key mathematical and computational approaches, and emphasising the role of the Hallmarks in current and future developments. We conclude with a discussion of interdisciplinary work, outlining areas of experimental interest which would benefit from the insight that mathematical and computational modelling can provide

Protein adsorption on heterogeneous surfaces

The adsorption of the protein bovine serum albumin from an aqueous solution onto substrata made from pure silica, pure zirconia, and a mixture of the two has revealed that the adsorption behavior of the protein onto the mixture very significantly diverges from the corresponding mean of the behaviors with the pure substrata. A tentative explanation in terms of matching substratum heterogeneity with protein surface heterogeneity is offered

Simulation pathway for estimating heat island influence on urban/suburban building space-conditioning loads and response to facade material changes

© 2019 Elsevier Ltd Environmental thermal loading on urban buildings is expected to increase owing to the combined influence of a warming climate, increasing frequency and severity of extreme heat events, and the urban heat island (UHI) effect. This paper presents how a computationally efficient estimation pathway could be utilised to understand UHI influence on building energy simulations. As an example, this is examined by considering UHI influence on the space-conditioning loads of office buildings within urban and suburban conditions, and how the trend of replacing heavyweight facades with lightweight alternatives could affect their surrounding microclimates, as well as building energy use. The paper addresses this through simulations of street canyons based on the urban Moorgate and suburban Wimbledon areas of London. Results show that with all scenarios including the UHI within a dynamic thermal simulation presents between 2.5 and 9.6% net increase in annual space-conditioning. The study also demonstrates that the trend in urban centres to replace heavyweight facades with lightweight insulated alternatives increases space-conditioning loads, which in turn increases UHI intensity to create a warming feedback loop. The study therefore stresses the significance of including microclimate loading from the UHI in estimating urban and suburban energy use, and the combined simulation approach is presented as a computationally efficient pathway for use by built environment designers

Strain Relaxation in Graded InGaAs and InP Buffer Layers on GaAs (001)

We investigate compositionally graded Inxo≤x≤0.5Ga1-xAs and InP buffer layers which are prepared by molecular beam epitaxy on (001) GaAs substrate. The initial In content xo is equal to 0, 0.12, 0.18, 0.24, and 0.5 for the different samples. The In composition of the graded buffer increases linearly between xo and 0.5 with a fixed slope of 50% In-content per μm. The idea was to combine the advantage of surface flatness in homogeneous buffer layers and the reduced density of threading dislocations on the surface for graded buffer layers. The best compromise in terms of photoluminescence intensity and linewidth, electron mobility and crystal quality is achieved for xo = 0.18. For comparison to the InGaAs layers, we investigated also homogenous InP buffer layers on GaAs substrate. A strong photoluminescence peak with a linewidth of 5 meV is observed for 1 μm InP grown at 450°C applying a GaP decomposition source. The density of threading dislocations in the surface region is lower than in relaxed In0.5Ga0.5As layers but still by far not as low as for the graded buffer layers

TRANSPORT AND INSTALLATION OF CRYO-MAGNETS IN CERN'S LARGE HADRON COLLIDER TUNNEL

The arcs of the Large Hadron Collider (LHC) will contain around 1700 main superconducting dipoles and quadrupoles. The long and heavy magnets are supported on fragile composite support posts inside a cryostat to reduce the heat in-leak to the magnets' super fluid helium bath. The presence of fragile components and the need to avoid geometry changes make the cryo-magnets very difficult to handle and transport. The transport and installation of the LHC cryo-magnets in the LEP tunnels originally designed for smaller, lighter LEP magnets has required development of completely new handling solutions. The paper explains the constraints imposed by the cryo-magnet characteristics, the existing tunnel infrastructure and schedule considerations. The development and realisation of transport and handling solutions are described, starting from conceptual design, through manufacture and testing to the installation of the first cryo-magnet. Integration studies to verify and reserve space needed for manoeuvre and the preparation of the infrastructure for transport and installation operations are also presented. The paper includes conclusions and some of the lessons learned

The immune system prevents recurrence of transplanted but not autochthonous antigenic tumors after oncogene inactivation therapy

Targeted oncogene inactivation by small molecule inhibitors can be very effective but tumor recurrence is a frequent problem in the clinic. Therapy by inactivation of the cancer-driving oncogene in transplanted tumors was shown to be augmented in the presence of T cells. However, these experiments did not take into account the long-term, usually tolerogenic, interaction of de novo malignancies with the immune system. Here, we employed mice, in which SV40 large T (Tag) and firefly luciferase (Luc) as fusion protein (TagLuc) could be regulated with the Tet-on system and upon activation resulted in tumors after a long latency. TagLuc inactivation induced profound tumor regression, demonstrating sustained oncogene addiction. While tumor relapse after TagLuc inactivation was prevented in immunocompetent mice bearing transplanted tumors, autochthonous tumors relapsed or recurred after therapy discontinuation indicating that the immune system that coevolved with the malignancy over an extended period of time lost the potency to mount an efficient anti-tumor immune response. By contrast, adoptively transferred CD8(+) T cells targeting the cancer-driving oncogene eradicated recurrent autochthonous tumors, highlighting a suitable therapy option in a clinically relevant model