Mice lacking NF-κB1 exhibit marked DNA damage responses and more severe gastric pathology in response to intraperitoneal tamoxifen administration

Tamoxifen (TAM) has recently been shown to cause acute gastric atrophy and metaplasia in mice. We have previously demonstrated that the outcome of Helicobacter felis infection, which induces similar gastric lesions in mice, is altered by deletion of specific NF-κB subunits. Nfkb1-/- mice developed more severe gastric atrophy than wild-type (WT) mice 6 weeks after H. felis infection. In contrast, Nfkb2-/- mice were protected from this pathology. We therefore hypothesized that gastric lesions induced by TAM may be similarly regulated by signaling via NF-κB subunits. Groups of five female C57BL/6 (WT), Nfkb1-/-, Nfkb2-/- and c-Rel-/- mice were administered 150 mg/kg TAM by IP injection. Seventy-two hours later, gastric corpus tissues were taken for quantitative histological assessment. In addition, groups of six female WT and Nfkb1-/- mice were exposed to 12 Gy γ-irradiation. Gastric epithelial apoptosis was quantified 6 and 48 h after irradiation. TAM induced gastric epithelial lesions in all strains of mice, but this was more severe in Nfkb1-/- mice than in WT mice. Nfkb1-/- mice exhibited more severe parietal cell loss than WT mice, had increased gastric epithelial expression of Ki67 and had an exaggerated gastric epithelial DNA damage response as quantified by γH2AX. To investigate whether the difference in gastric epithelial DNA damage response of Nfkb1-/- mice was unique to TAM-induced DNA damage or a generic consequence of DNA damage, we also assessed gastric epithelial apoptosis following γ-irradiation. Six hours after γ-irradiation, gastric epithelial apoptosis was increased in the gastric corpus and antrum of Nfkb1-/- mice. NF-κB1-mediated signaling regulates the development of gastric mucosal pathology following TAM administration. This is associated with an exaggerated gastric epithelial DNA damage response. This aberrant response appears to reflect a more generic sensitization of the gastric mucosa of Nfkb1-/- mice to DNA damage

Controlling Magnetic Anisotropy in a Zero-Dimensional S=1 Magnet Using Isotropic Cation Substitution

The [Zn_{1–x}_Ni-{x}(HF_{2})(pyz)_{2}]SbF_{6} (x = 0.2; pyz = pyrazine) solid solution exhibits a zero-field splitting (D) that is 22% larger [D = 16.2(2) K (11.3(2) cm^{–1})] than that observed in the x = 1 material [D = 13.3(1) K (9.2(1) cm^{–1)}]. The substantial change in D is accomplished by an anisotropic lattice expansion in the MN_{4} (M = Zn or Ni) plane, wherein the increased concentration of isotropic Zn(II) ions induces a nonlinear variation in M-F and M-N bond lengths. In this, we exploit the relative donor atom hardness, where M-F and M-N form strong ionic and weak coordinate covalent bonds, respectively, the latter being more sensitive to substitution of Ni by the slightly larger Zn(II) ion. In this way, we are able to tune the single-ion anisotropy of a magnetic lattice site by Zn-substitution on nearby sites. This effect has possible applications in the field of single-ion magnets and the design of other molecule-based magnetic systems

Electrostatically gated membrane permeability in inorganic protocells

Although several strategies are now available to produce functional microcompartments analogous to primitive cell-like structures, little progress has been made in generating protocell constructs with self-controlled membrane permeability. Here we describe the preparation of water-dispersible colloidosomes based on silica nanoparticles and delineated by a continuous semipermeable inorganic membrane capable of self-activated, electrostatically gated permeability. We use crosslinking and covalent grafting of a pH-responsive copolymer to generate an ultrathin elastic membrane that exhibits selective release and uptake of small molecules. This behaviour, which depends on the charge of the copolymer coronal layer, serves to trigger enzymatic dephosphorylation reactions specifically within the protocell aqueous interior. This system represents a step towards the design and construction of alternative types of artificial chemical cells and protocell models based on spontaneous processes of inorganic self-organization

Detecting Variability in Massive Astronomical Time-Series Data I: application of an infinite Gaussian mixture model

We present a new framework to detect various types of variable objects within massive astronomical time-series data. Assuming that the dominant population of objects is non-variable, we find outliers from this population by using a non-parametric Bayesian clustering algorithm based on an infinite GaussianMixtureModel (GMM) and the Dirichlet Process. The algorithm extracts information from a given dataset, which is described by six variability indices. The GMM uses those variability indices to recover clusters that are described by six-dimensional multivariate Gaussian distributions, allowing our approach to consider the sampling pattern of time-series data, systematic biases, the number of data points for each light curve, and photometric quality. Using the Northern Sky Variability Survey data, we test our approach and prove that the infinite GMM is useful at detecting variable objects, while providing statistical inference estimation that suppresses false detection. The proposed approach will be effective in the exploration of future surveys such as GAIA, Pan-Starrs, and LSST, which will produce massive time-series data.Comment: accepted for publication in MNRA

The relationship between endogenous thymidine concentrations and [F-18]FLT uptake in a range of preclinical tumour models

BACKGROUND: Recent studies have shown that 3′-deoxy-3′-[18F] fluorothymidine ([18F]FLT)) uptake depends on endogenous tumour thymidine concentration. The purpose of this study was to investigate tumour thymidine concentrations and whether they correlated with [18F]FLT uptake across a broad spectrum of murine cancer models. A modified liquid chromatography-mass spectrometry (LC-MS/MS) method was used to determine endogenous thymidine concentrations in plasma and tissues of tumour-bearing and non-tumour bearing mice and rats. Thymidine concentrations were determined in 22 tumour models, including xenografts, syngeneic and spontaneous tumours, from six research centres, and a subset was compared for [18F]FLT uptake, described by the maximum and mean tumour-to-liver uptake ratio (TTL) and SUV. RESULTS: The LC-MS/MS method used to measure thymidine in plasma and tissue was modified to improve sensitivity and reproducibility. Thymidine concentrations determined in the plasma of 7 murine strains and one rat strain were between 0.61 ± 0.12 μM and 2.04 ± 0.64 μM, while the concentrations in 22 tumour models ranged from 0.54 ± 0.17 μM to 20.65 ± 3.65 μM. TTL at 60 min after [18F]FLT injection, determined in 14 of the 22 tumour models, ranged from 1.07 ± 0.16 to 5.22 ± 0.83 for the maximum and 0.67 ± 0.17 to 2.10 ± 0.18 for the mean uptake. TTL did not correlate with tumour thymidine concentrations. CONCLUSIONS: Endogenous tumour thymidine concentrations alone are not predictive of [18F]FLT uptake in murine cancer models

Comparing orbiter and rover image-based mapping of an ancient sedimentary environment, Aeolis Palus, Gale crater, Mars

This study provides the first systematic comparison of orbital facies maps with detailed ground-based geology observations from the Mars Science Laboratory (MSL) Curiosity rover to examine the validity of geologic interpretations derived from orbital image data. Orbital facies maps were constructed for the Darwin, Cooperstown, and Kimberley waypoints visited by the Curiosity rover using High Resolution Imaging Science Experiment (HiRISE) images. These maps, which represent the most detailed orbital analysis of these areas to date, were compared with rover image-based geologic maps and stratigraphic columns derived from Curiosity's Mast Camera (Mastcam) and Mars Hand Lens Imager (MAHLI). Results show that bedrock outcrops can generally be distinguished from unconsolidated surficial deposits in high-resolution orbital images and that orbital facies mapping can be used to recognize geologic contacts between well-exposed bedrock units. However, process-based interpretations derived from orbital image mapping are difficult to infer without known regional context or observable paleogeomorphic indicators, and layer-cake models of stratigraphy derived from orbital maps oversimplify depositional relationships as revealed from a rover perspective. This study also shows that fine-scale orbital image-based mapping of current and future Mars landing sites is essential for optimizing the efficiency and science return of rover surface operations

Vectorial dissipative solitons in vertical-cavity surface-emitting Lasers with delays

We show that the nonlinear polarization dynamics of a vertical-cavity surface-emitting laser placed into an external cavity leads to the formation of temporal vectorial dissipative solitons. These solitons arise as cycles in the polarization orientation, leaving the total intensity constant. When the cavity round-trip is much longer than their duration, several independent solitons as well as bound states (molecules) may be hosted in the cavity. All these solutions coexist together and with the background solution, i.e. the solution with zero soliton. The theoretical proof of localization is given by the analysis of the Floquet exponents. Finally, we reduce the dynamics to a single delayed equation for the polarization orientation allowing interpreting the vectorial solitons as polarization kinks.Comment: quasi final resubmission version, 12 pages, 9 figure

National profile of foot orthotic provision in the United Kingdom, part 1 : practitioners and scope of practice.

Foot orthoses have been advocated in the management of a wide range of clinical foot and lower limb problems and are within the scope of podiatry, orthotic and physiotherapy practice. Previous reports into the provision of orthoses have consistently identified significant issues with services and devices, but data were never specific to foot orthoses. The aim of this first of a series of papers was to report the first ever national multi professional profile of foot orthosis provision in the United Kingdom. Quantitative and qualitative data were collected from podiatrists, orthotists and physiotherapists via an online questionnaire. The topics, questions and answers were developed through a series of pilot phases. The professions were targeted through electronic and printed materials. Data were captured over a 10 month period in 2016. A total of 499 responses were included in analysis, including 357 podiatrists, 93 orthotists and 49 physiotherapists. The results reveal wide ranging practices across podiatrists, orthotists and physiotherapists, provision of orthoses through different health care departments (uni and multidisciplinary), for different health conditions (acute and chronic), and involving different types of orthoses (prefabricated and customised). Foot orthoses in the United Kingdom are provided in areas of well recognised health and rehabilitation priorities. A wide range of orthotic devices and practices are employed and different professions provide foot orthoses in different ways

Factors influencing uptake of voluntary counselling and testing services for HIV/AIDS in the Lower Manya Krobo Municipality (LMKM) in the Eastern Region of Ghana: a cross-sectional household survey

Background Voluntary counselling and testing (VCT) is one of the nine strategies recommended for prevention and control of HIV globally. In this study, we assessed the awareness and utilisation of VCT services among residents of the Lower Manya Krobo Municipality (LMKM) in the Eastern Region of Ghana. Methods A population-based descriptive cross-sectional survey was conducted with 200 participants, aged between 18 and 55 years. Participants were recruited using cluster and simple random techniques to take part in the survey. Data was analysed descriptively, as well as using regression analysis approach. Results Ninety-one percent of the respondents surveyed were aware of VCT services for HIV/AIDS. Seventy percent (70 %) have used VCT service in the last 12 months prior to the survey. Of this proportion, 97 % were satisfied with the quality of VCT services offered and indicated their willingness to recommend the service to others. Participants desire to know their HIV status (40 %), referral by health workers (25 %), and participants who wanted to get married (11 %) were the main reasons for increased uptake. Participants who had formal education, primary (OR = 1.8 (95 % CI 1.25–2.84)), junior high school (OR = 2.3 (95 % CI 1.54–3.37)), senior high school (OR = 2.8 (95 % CI 1.73–4.78)), and tertiary (OR = 3.4 (95 % CI 1.98–8.42)), had increased chance of using VCT service compared with participants who had no education (p < 0.001). Reasons for non-utilisation of VCT service were lack of awareness of the VCT service in the area (32 %), fear of being stigmatised (53 %), and the belief that HIV/AIDS cannot be cured and therefore the lack of need (5 %). Conclusions Although awareness and utilisation of VCT service rates were reportedly high, more efforts need to be done in order to increase awareness and promote utilisation. HIV/AIDS educational campaign programmes need to be strongly pursued, with emphasis on the benefits of VCT services. This has the potential of reducing stigma and increase utilisation