A Geographic Information Systems Approach to the 19th Century Excavation of Brixham Cavern, Devon, England

The oldest known spatially-explicit archaeological excavation, conducted in Brixham cave, Devon, in 1858, is reconstructed using geographic information systems technology. Two dimensional plots of individual fossil taxa and flint artefacts demonstrate the utility of the technique for elucidating taphonomy and palaeobiology. The cave served as a den for hibernating brown bears, as a den for hyena and cave lion, and as a reliquary for their prey

Assessment of cold neutron radiography capability

This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). The authors goals were to demonstrate and assess cold neutron radiography techniques at the Los Alamos Neutron Science Center (LANSCE), Manual Lujan Neutron Scattering Center (Lujan Center), and to investigate potential applications of the capability. The authors have obtained images using film and an amorphous silicon detector. In addition, a new technique they have developed allows neutron radiographs to be made using only a narrow range of neutron energies. Employing this approach and the Bragg cut-off phenomena in certain materials, they have demonstrated material discrimination in radiography. They also demonstrated the imaging of cracks in a sample of a fire-set case that was supplied by Sandia National Laboratory, and they investigated whether the capability could be used to determine the extent of coking in jet engine nozzles. The LANSCE neutron radiography capability appears to have applications in the DOE stockpile maintenance and science-based stockpile stewardship (SBSS) programs, and in industry

Macrostrain measurement using radial collimators at LANSCE

A series of `short` radial collimators have been implemented in the 90{degrees} scattering geometries on the neutron powder diffractometer at Los Alamos. The capability to perform macrostrain measurements has been improved by the commensurate ability to rapidly select a sampling volume appropriate to the specimen. The compact design of the collimators was dictated by the need to fit them in a cylindrical vacuum chamber as well as providing space in which to manipulate a specimen in three dimensions. Collimators of different vane lengths were fabricated to give 4 different resolutions for which 2/3 of the diffracted intensity comes form distances of 0.75, 1. 25, 2.5, and 4.0 mm along the incident beam. Qualifying scans and a demonstration of a cracked ring, containing a steep stress gradient, are included

Design and Implementation of an X-Ray Strain Measurement Capability Using a Rotating Anode Machine

This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). Residual stresses close to the surface can improve the reliability and lifetime of parts for technological applications. X-ray diffraction plays a significant role in gaining an exact knowledge of the stresses at the surface and their depth distribution. An x-ray capability at Los Alamos is key to developing and maintaining industrial collaborations in strain effects. To achieve this goal, the authors implemented a residual strain measuring station on the rotating anode x-ray instrument at the Lujan Center. This capability has been used to investigate residual strains in heat treated automotive components, machining effects on titanium alloys, resistance welded steel joints, titanium matrix fiber reinforced composites, ceramic matrix composites, thin films, and ceramic coatings. The overall objective is to combine both x-ray and neutron diffraction measurements with numerical models (e.g., finite element calculations)

Mechanical properties of NiTi-TiC shape-memory composites

This paper reviews recent work on the mechanical behavior of martensitic NiTi composites reinforced with 10--20 vol.% TiC particulates. The behavior of the composites is compared to that of unreinforced NiTi, so as to elucidate the effect of mismatch due to matrix transformation, thermal expansion, twinning or slip, in the presence of purely elastic particles. The twinning and subsequent thermal recovery of deformed composites, measured both macroscopically (by compressive testing and by dilatometry) and microscopically (by neutron diffraction), are summarized

UV Circular Polarisation in Star Formation Regions : The Origin of Homochirality?

Ultraviolet circularly polarised light has been suggested as the initial cause of the homochirality of organic molecules in terrestrial organisms, via enantiomeric selection of prebiotic molecules by asymmetric photolysis. We present a theoretical investigation of mechanisms by which ultraviolet circular polarisation may be produced in star formation regions. In the scenarios considered here, light scattering produces only a small percentage of net circular polarisation at any point in space, due to the forward throwing nature of the phase function in the ultraviolet. By contrast, dichroic extinction can produce a fairly high percentage of net circular polarisation (∼10%) and may therefore play a key role in producing an enantiomeric excessPeer reviewe

Labrador retrievers under primary veterinary care in the UK: demography, mortality and disorders

Abstract Background Labrador retrievers are reportedly predisposed to many disorders but accurate prevalence information relating to the general population are lacking. This study aimed to describe demography, mortality and commonly recorded diseases in Labrador retrievers under UK veterinary care. Methods The VetCompass™ programme collects electronic patient record data on dogs attending UK primary-care veterinary practices. Demographic analysis covered all33,320 Labrador retrievers in the VetCompass™ database under veterinary care during 2013 while disorder and mortality data were extracted from a random sample of 2074 (6.2%) of these dogs. Results Of the Labrador retrievers with information available, 15,427 (46.4%) were female and 15,252 (53.6%) were male. Females were more likely to be neutered than males (59.7% versus 54.8%, P <  0.001). The overall mean adult bodyweight was 33.0 kg (SD 6.1). Adult males were heavier (35.2 kg, SD 5.9 kg) than adult females (30.4 kg, SD 5.2 kg) (P <  0.001). The median longevity of Labrador retrievers overall was 12.0 years (IQR 9.9–13.8, range 0.0–16.0). The most common recorded colours were black (44.6%), yellow (27.8%) and liver/chocolate (reported from hereon as chocolate) (23.8%). The median longevity of non-chocolate coloured dogs (n = 139, 12.1 years, IQR 10.2–13.9, range 0.0–16.0) was longer than for chocolate coloured animals (n = 34, 10.7 years, IQR 9.0–12.4, range 3.8–15.5) (P = 0.028). Of a random sample of 2074 (6.2%) Labrador retrievers under care in 2013 that had full disorder data extracted, 1277 (61.6%) had at least one disorder recorded. The total number of dogs who died at any date during the study was 176. The most prevalent disorders recorded were otitis externa (n = 215, prevalence 10.4%, 95% CI: 9.1–11.8), overweight/obesity (183, 8.8%, 95% CI: 7.6–10.1) and degenerative joint disease (115, 5.5%, 95% CI: 4.6–6.6). Overweight/obesity was not statistically significantly associated with neutering in females (8.3% of entire versus 12.5% of neutered, P = 0.065) but was associated with neutering in males (4.1% of entire versus 11.4% of neutered, P < 0.001). The prevalence of otitis externa in black dogs was 12.8%, in yellow dogs it was 17.0% but, in chocolate dogs, it rose to 23.4% (P < 0.001). Similarly, the prevalence of pyo-traumatic dermatitis in black dogs was 1.1%, in yellow dogs it was 1.6% but in chocolate dogs it rose to 4.0% (P = 0.011). Conclusions The current study assists prioritisation of health issues within Labrador retrievers. The most common disorders were overweight/obesity, otitis externa and degenerative joint disease. Males were significantly heavier females. These results can alert prospective owners to potential health issues and inform breed-specific wellness checks

Structural neural networks subserving oculomotor function in first-episode schizophrenia

BACKGROUND: Smooth pursuit and antisaccade abnormalities are well documented in schizophrenia, but their neuropathological correlates remain unclear. METHODS: In this study, we used statistical parametric mapping to investigate the relationship between oculomotor abnormalities and brain structure in a sample of first-episode schizophrenia patients (n = 27). In addition to conventional volumetric magnetic resonance imaging, we also used magnetization transfer ratio, a technique that allows more precise tissue characterization. RESULTS: We found that smooth pursuit abnormalities were associated with reduced magnetization transfer ratio in several regions, predominantly in the right prefrontal cortex. Antisaccade errors correlated with gray matter volume in the right medial superior frontal cortex as measured by conventional magnetic resonance imaging but not with magnetization transfer ratio. CONCLUSIONS: These preliminary results demonstrate that specific structural abnormalities are associated with abnormal eye movements in schizophrenia

STING agonism overcomes STAT3-mediated immunosuppression and adaptive resistance to PARP inhibition in ovarian cancer

BackgroundPoly (ADP-ribose) polymerase (PARP) inhibition (PARPi) has demonstrated potent therapeutic efficacy in patients with BRCA-mutant ovarian cancer. However, acquired resistance to PARPi remains a major challenge in the clinic.MethodsPARPi-resistant ovarian cancer mouse models were generated by long-term treatment of olaparib in syngeneic Brca1-deficient ovarian tumors. Signal transducer and activator of transcription 3 (STAT3)-mediated immunosuppression was investigated in vitro by co-culture experiments and in vivo by analysis of immune cells in the tumor microenvironment (TME) of human and mouse PARPi-resistant tumors. Whole genome transcriptome analysis was performed to assess the antitumor immunomodulatory effect of STING (stimulator of interferon genes) agonists on myeloid cells in the TME of PARPi-resistant ovarian tumors. A STING agonist was used to overcome STAT3-mediated immunosuppression and acquired PARPi resistance in syngeneic and patient-derived xenografts models of ovarian cancer.ResultsIn this study, we uncover an adaptive resistance mechanism to PARP inhibition mediated by tumor-associated macrophages (TAMs) in the TME. Markedly increased populations of protumor macrophages are found in BRCA-deficient ovarian tumors that rendered resistance to PARPi in both murine models and patients. Mechanistically, PARP inhibition elevates the STAT3 signaling pathway in tumor cells, which in turn promotes protumor polarization of TAMs. STAT3 ablation in tumor cells mitigates polarization of protumor macrophages and increases tumor-infiltrating T cells on PARP inhibition. These findings are corroborated in patient-derived, PARPi-resistant BRCA1-mutant ovarian tumors. Importantly, STING agonists reshape the immunosuppressive TME by reprogramming myeloid cells and overcome the TME-dependent adaptive resistance to PARPi in ovarian cancer. This effect is further enhanced by addition of the programmed cell death protein-1 blockade.ConclusionsWe elucidate an adaptive immunosuppression mechanism rendering resistance to PARPi in BRCA1-mutant ovarian tumors. This is mediated by enrichment of protumor TAMs propelled by PARPi-induced STAT3 activation in tumor cells. We also provide a new strategy to reshape the immunosuppressive TME with STING agonists and overcome PARPi resistance in ovarian cancer.Peer reviewe