ERTS-1 image enhancement by optically combining density slices

The technique of density slicing using a photographic film and its application to enhancement of ERTS-1 imagery has proved to be useful for mapping varigated areal phenomena and provides a useful supplement ot the I2S MiniAddcol viewing system. The intial experiments conducted with this film were encouraging, and indicated that this technique of density slicing using readily accessible darkroom facilities and simple darkroom procedures allows rapid, accurate, and facile interpretation of certain areal phenomena to be made from the imagery. The distribution of the tree yucca, Yucca brevifolia Jaegeriana, in the eastern Mojave Desert of Southern California and southern Nevada was used as an example to test the accuracy of the technique for mapping purposes. The distribution was mapped at a relatively high level of accuracy

Campylobacter jejuni Transmission from Pet Animals: A New Zoonosis?

In recent years, Campylobacter jejuni has been recognized as an important enteric pathogen of human beings causing acute and subacute gastrointestinal illness. Recent reports have suggested that infected household pets may be vectors for the human infection. It has been theorized that as more research will be conducted\u27 the zoonotic implications of C. jejuni will rival and probably exceed those of salmonellosis. Therefore, as veterinarians, it is important to be aware of the disease in animals, the zoonotic implications, and be able to advise our clientele

Demonstration of FPGA acceleration of Monte Carlo simulation

We present results from a stand-alone simulation of electron single Coulomb scattering as implemented completely on an Field Programmable Gate Array (FPGA) architecture and compared with an identical simulation on a standard CPU. FPGA architectures offer unprecedented speed-up capability for Monte Carlo simulations, however with the caveats of lengthy development cycles and resource limitation, particularly in terms of on-chip memory and DSP blocks. As a proof of principle of acceleration on an FPGA, we chose a single scattering process of electrons in water at an energy of 6 MeV. The initial code-base was implemented in C++ and optimised for CPU processing. To measure the potential performance gains of FPGAs compared to modern multi-core CPUs we computed 100M histories of a 6 MeV electron interacting in water. Without performing any hardware-specific optimisation, the results show that the FPGA implementation is over 110 times faster than an optimised parallel implementation running on 12 CPU-cores, and over 270 times faster than a sequential single-core CPU implementation. The results on both architectures were statistically equivalent. The successful implementation and acceleration results are very encouraging for the future exploitation of more sophisticated Monte Carlo simulation on FPGAs for High Energy Physics applications

The Sodium Channel beta4 Auxiliary Subunit Selectively Controls Long-Term Depression in Core Nucleus Accumbens Medium Spiny Neurons

Voltage-gated sodium channels are essential for generating the initial rapid depolarization of neuronal membrane potential during action potentials (APs) that enable cell-to-cell communication, the propagation of signals throughout the brain, and the induction of synaptic plasticity. Although all brain neurons express one or several variants coding for the core pore-forming sodium channel alpha subunit, the expression of the beta (beta1-4) auxiliary subunits varies greatly. Of particular interest is the beta4 subunit, encoded by the Scn4b gene, that is highly expressed in dorsal and ventral (i.e., nucleus accumbens - NAc) striata compared to other brain regions, and that endows sodium channels with unique gating properties. However, its role on neuronal activity, synaptic plasticity, and behaviors related to drugs of abuse remains poorly understood. Combining whole-cell patch-clamp recordings with two-photon calcium imaging in Scn4b knockout (KO) and knockdown mice, we found that Scn4b altered the properties of APs in core accumbens medium spiny neurons (MSNs). These alterations are associated with a reduction of the probability of MSNs to evoke spike-timing-dependent long-term depression (tLTD) and a reduced ability of backpropagating APs to evoke dendritic calcium transients. In contrast, long-term potentiation (tLTP) remained unaffected. Interestingly, we also showed that amphetamine-induced locomotor activity was significantly reduced in male Scn4b KO mice compared to wild-type controls. Taken together, these data indicate that the Scn4b subunit selectively controls tLTD by modulating dendritic calcium transients evoked by backpropagating APs

miRNAome analysis of the mammalian neuronal nicotinic acetylcholine receptor gene family

Nicotine binds to and activates a family of ligand-gated ion channels, neuronal nicotinic acetylcholine receptors (nAChRs). Chronic nicotine exposure alters the expression of various nAChR subtypes, which likely contributes to nicotine dependence; however, the underlying mechanisms regulating these changes remain unclear. A growing body of evidence indicates that microRNAs (miRNAs) may be involved in nAChR regulation. Using bioinformatics, miRNA library screening, site-directed mutagenesis, and gene expression analysis, we have identified a limited number of miRNAs that functionally interact with the 3\u27-untranslated regions (3\u27 UTRs) of mammalian neuronal nAChR subunit genes. In silico analyses revealed specific, evolutionarily conserved sites within the 3\u27 UTRs through which the miRNAs regulate gene expression. Mutating these sites disrupted miRNA regulation confirming the in silico predictions. In addition, the miRNAs that target nAChR 3\u27 UTRs are expressed in mouse brain and are regulated by chronic nicotine exposure. Furthermore, we show that expression of one of these miRNAs, miR-542-3p, is modulated by nicotine within the mesocorticolimbic reward pathway. Importantly, overexpression of miR-542-3p led to a decrease in the protein levels of its target, the nAChR beta2 subunit. Bioinformatic analysis suggests that a number of the miRNAs play a general role in regulating cholinergic signaling. Our results provide evidence for a novel mode of nicotine-mediated regulation of the mammalian nAChR gene family

miRNAome analysis of the mammalian neuronal nicotinic acetylcholine receptor gene family

Nicotine binds to and activates a family of ligand-gated ion channels, neuronal nicotinic acetylcholine receptors (nAChRs). Chronic nicotine exposure alters the expression of various nAChR subtypes, which likely contributes to nicotine dependence; however, the underlying mechanisms regulating these changes remain unclear. A growing body of evidence indicates that microRNAs (miRNAs) may be involved in nAChR regulation. Using bioinformatics, miRNA library screening, site-directed mutagenesis, and gene expression analysis, we have identified a limited number of miRNAs that functionally interact with the 3\u27-untranslated regions (3\u27 UTRs) of mammalian neuronal nAChR subunit genes. In silico analyses revealed specific, evolutionarily conserved sites within the 3\u27 UTRs through which the miRNAs regulate gene expression. Mutating these sites disrupted miRNA regulation confirming the in silico predictions. In addition, the miRNAs that target nAChR 3\u27 UTRs are expressed in mouse brain and are regulated by chronic nicotine exposure. Furthermore, we show that expression of one of these miRNAs, miR-542-3p, is modulated by nicotine within the mesocorticolimbic reward pathway. Importantly, overexpression of miR-542-3p led to a decrease in the protein levels of its target, the nAChR beta2 subunit. Bioinformatic analysis suggests that a number of the miRNAs play a general role in regulating cholinergic signaling. Our results provide evidence for a novel mode of nicotine-mediated regulation of the mammalian nAChR gene family

Therapeutic targeting of integrin αvβ6 in breast cancer

BACKGROUND: Integrin ?v?6 promotes migration, invasion, and survival of cancer cells; however, the relevance and role of ?v?6 has yet to be elucidated in breast cancer.METHODS: Protein expression of integrin subunit beta6 (?6) was measured in breast cancers by immunohistochemistry (n &gt; 2000) and ITGB6 mRNA expression measured in the Molecular Taxonomy of Breast Cancer International Consortium dataset. Overall survival was assessed using Kaplan Meier curves, and bioinformatics statistical analyses were performed (Cox proportional hazards model, Wald test, and Chi-square test of association). Using antibody (264RAD) blockade and siRNA knockdown of ?6 in breast cell lines, the role of ?v?6 in Human Epidermal Growth Factor Receptor 2 (HER2) biology (expression, proliferation, invasion, growth in vivo) was assessed by flow cytometry, MTT, Transwell invasion, proximity ligation assay, and xenografts (n ? 3), respectively. A student's t-test was used for two variables; three-plus variables used one-way analysis of variance with Bonferroni's Multiple Comparison Test. Xenograft growth was analyzed using linear mixed model analysis, followed by Wald testing and survival, analyzed using the Log-Rank test. All statistical tests were two sided.RESULTS: High expression of either the mRNA or protein for the integrin subunit ?6 was associated with very poor survival (HR = 1.60, 95% CI = 1.19 to 2.15, P = .002) and increased metastases to distant sites. Co-expression of ?6 and HER2 was associated with worse prognosis (HR = 1.97, 95% CI = 1.16 to 3.35, P = .01). Monotherapy with 264RAD or trastuzumab slowed growth of MCF-7/HER2-18 and BT-474 xenografts similarly (P &lt; .001), but combining 264RAD with trastuzumab effectively stopped tumor growth, even in trastuzumab-resistant MCF-7/HER2-18 xenografts.CONCLUSIONS: Targeting ?v?6 with 264RAD alone or in combination with trastuzumab may provide a novel therapy for treating high-risk and trastuzumab-resistant breast cancer patients.<br/

Exploratory randomised controlled trial of a mindfulness-based weight loss intervention for women

To explore the efficacy of a mindfulness-based weight loss intervention for women. Sixty-two women (ages 19-64; BMI 22.5-52.1) who were attempting to lose weight were randomised to an intervention or control condition. The former were invited to attend four 2-h workshops, the latter were asked to continue with their normal diets. Data were collected at baseline, 4 and 6 months. BMI, physical activity, mental health. At 6 months intervention participants showed significantly greater increases in physical activity compared to controls (p<.05) but no significant differences in weight loss or mental health. However, when intervention participants who reported 'never' applying the workshop principles at 6 months (n=7) were excluded, results showed both significantly greater increases in physical activity (3.1 sessions per week relative to controls, p<.05) and significantly greater reductions in BMI (0.96 relative to controls, equivalent to 2.32 kg, p<0.5). Reductions in BMI were mediated primarily by reductions in binge eating. Despite its brevity, the intervention was successful at bringing about change. Further refinements should increase its efficacy

Development of childhood asthma prediction models using machine learning approaches

Background: Respiratory symptoms are common in early life and often transient. It is difficult to identify in which children these will persist and result in asthma. Machine learning (ML) approaches have the potential for better predictive performance and generalisability over existing childhood asthma prediction models. This study applied ML approaches to predict school-age asthma (age 10) in early life (Childhood Asthma Prediction in Early life, CAPE model) and at preschool age (Childhood Asthma Prediction at Preschool age, CAPP model). Methods: Clinical and environmental exposure data was collected from children enrolled in the Isle of Wight Birth Cohort (N = 1368, ∼15% asthma prevalence). Recursive Feature Elimination (RFE) identified an optimal subset of features predictive of school-age asthma for each model. Seven state-of-the-art ML classification algorithms were used to develop prognostic models. Training was performed by applying fivefold cross-validation, imputation, and resampling. Predictive performance was evaluated on the test set. Models were further externally validated in the Manchester Asthma and Allergy Study (MAAS) cohort. Results: RFE identified eight and twelve predictors for the CAPE and CAPP models, respectively. Support Vector Machine (SVM) algorithms provided the best performance for both the CAPE (area under the receiver operating characteristic curve, AUC = 0.71) and CAPP (AUC = 0.82) models. Both models demonstrated good generalisability in MAAS (CAPE 8-year = 0.71, 11-year = 0.71, CAPP 8-year = 0.83, 11-year = 0.79) and excellent sensitivity to predict a subgroup of persistent wheezers. Conclusion: Using ML approaches improved upon the predictive performance of existing regression-based models, with good generalisability and ability to rule in asthma and predict persistent wheeze.</p

Genetic variation at MECOM, TERT, JAK2 and HBS1L-MYB predisposes to myeloproliferative neoplasms

Clonal proliferation in myeloproliferative neoplasms (MPN) is driven by somatic mutations in JAK2, CALR or MPL, but the contribution of inherited factors is poorly characterized. Using a three-stage genome-wide association study of 3,437 MPN cases and 10,083 controls, we identify two SNPs with genome-wide significance in JAK2V617F-negative MPN: rs12339666 (JAK2; meta-analysis P=1.27 × 10−10) and rs2201862 (MECOM; meta-analysis P=1.96 × 10−9). Two additional SNPs, rs2736100 (TERT) and rs9376092 (HBS1L/MYB), achieve genome-wide significance when including JAK2V617F-positive cases. rs9376092 has a stronger effect in JAK2V617F-negative cases with CALR and/or MPL mutations (Breslow–Day P=4.5 × 10−7), whereas in JAK2V617F-positive cases rs9376092 associates with essential thrombocythemia (ET) rather than polycythemia vera (allelic χ2 P=7.3 × 10−7). Reduced MYB expression, previously linked to development of an ET-like disease in model systems, associates with rs9376092 in normal myeloid cells. These findings demonstrate that multiple germline variants predispose to MPN and link constitutional differences in MYB expression to disease phenotype