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Background BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) for breast cancer and the epithelial tubo-ovarian cancer (EOC) models included in the CanRisk tool (www.canrisk. org) provide future cancer risks based on pathogenic variants in cancer-susceptibility genes, polygenic risk scores, breast density, questionnaire-based risk factors and family history. Here, we extend the models to include the effects of pathogenic variants in recently established breast cancer and EOC susceptibility genes, up-to-date age-specific pathology distributions and continuous risk factors. Methods BOADICEA was extended to further incorporate the associations of pathogenic variants in BARD1, RAD51C and RAD51D with breast cancer risk. The EOC model was extended to include the association of PALB2 pathogenic variants with EOC risk. Age-specific distributions of oestrogen-receptor-negative and triplenegative breast cancer status for pathogenic variant carriers in these genes and CHEK2 and ATM were also incorporated. A novel method to include continuous risk factors was developed, exemplified by including adult height as continuous. Results BARD1, RAD51C and RAD51D explain 0.31% of the breast cancer polygenic variance. When incorporated into the multifactorial model, 34%–44% of these carriers would be reclassified to the nearpopulation and 15%–22% to the high-risk categories based on the UK National Institute for Health and Care Excellence guidelines. Under the EOC multifactorial model, 62%, 35% and 3% of PALB2 carriers have lifetime EOC risks of <5%, 5%–10% and >10%, respectively. Including height as continuous, increased the breast cancer relative risk variance from 0.002 to 0.010. Conclusions These extensions will allow for better personalised risks for BARD1, RAD51C, RAD51D and PALB2 pathogenic variant carriers and more informed choices on screening, prevention, risk factor modification or other risk-reducing options. [ABSTRACT FROM AUTHOR]

The first International Workshop of the ATM and Cancer Risk group focusing on the role of Ataxia-Telangiectasia Mutated (ATM) gene in cancer was held on December 4 and 5, 2019 at Institut Curie in Paris, France. It was motivated by the fact that germline ATM pathogenic variants have been found to be associated with different cancer types. However, due to the lack of precise age-, sex-, and site-specific risk estimates, no consensus on management guidelines for variant carriers exists, and the clinical utility of ATM variant testing is uncertain. The meeting brought together epidemiologists, geneticists, biologists and clinicians to review current knowledge and on-going challenges related to ATM and cancer risk. This report summarizes the meeting sessions content that covered the latest results in family-based and population-based studies, the importance of accurate variant classification, the effect of radiation exposures for ATM variant carriers, and the characteristics of ATM-deficient tumors. The report concludes that ATM variant carriers outside of the context of Ataxia-Telangiectasia may benefit from effective cancer risk management and therapeutic strategies and that efforts to set up large-scale studies in the international framework to achieve this goal are necessary. [ABSTRACT FROM AUTHOR]

Background: Epidemiological investigations have established unhealthy lifestyles, such as excessive leisurely sedentary behavior (especially TV/television watching) and breakfast skipping, increase the risk of type 2 diabetes (T2D), but the causal relationship is unclear. We aimed to understand how single nucleotide variants contribute to the co-occurrence of unhealthy lifestyles and T2D, thereby providing meaningful insights into disease mechanisms. Methods: Combining summary statistics from genome-wide association studies (GWAS) on TV watching (N = 422218), breakfast skipping (N = 193860) and T2D (N = 159208) in European pedigrees, we conducted comprehensive pairwise genetic analysis, including high-definition likelihood (HDL-method), cross-phenotype association studies (CPASSOC), GWAS-eQTL colocalization analysis and transcriptome-wide association studies (TWAS), to understand the genetic overlap between them. We also performed bidirectional two-sample Mendelian randomization (MR) analysis for causal inference using genetic instrumental variables, and two-step MR mediation analysis was used to assess any effects explained by body mass index, lipid traits and glycemic traits. Results: HDL-method showed that T2D shared a strong genetic correlation with TV watching (rg = 0.26; P = 1.63×10-29) and skipping breakfast (rg = 0.15; P =2.02×10-6). CPASSOC identifies eight independent SNPs shared between T2D and TV watching, including one novel shared locus. TWAS and CPASSOC showed that shared genes were enriched in lung, esophageal, adipose, and thyroid tissues and highlighted potential shared regulatory pathways for lipoprotein metabolism, pancreatic β-cell function, cellular senescence and multi-mediator factors. MR showed TV watching had a causal effect on T2D (βIVW = 0.629, P IVW = 1.80×10-10), but no significant results were observed between breakfast skipping and T2D. Mediation analysis provided evidence that body mass index, fasting glucose, hemoglobin A1c and high-density lipoprotein are potential factors that mediate the causal relationship between TV and T2D. Conclusions: Our findings provide strong evidence of shared genetics and causation between TV watching and T2D and facilitate our identification of common genetic architectures shared between them. [ABSTRACT FROM AUTHOR]

Declines in pollinating invertebrates across intensively cultivated landscapes linked to reductions in flower‐rich habitats constitute a key threat to biodiversity conservation and the provision of ecosystem services. Over recent decades, many ponds in agricultural landscapes have become overgrown with woody vegetation, resulting in heavily shaded, flower‐poor pond basins and margins. Restoration of farmland ponds through removal of sediment and encroaching woody vegetation (canopy management) from pond margins greatly enhances freshwater biodiversity. Nevertheless, the consequences of pond management for pond‐margin plants and pollinating insects remain poorly understood. Here, we studied these effects for ponds in Norfolk, eastern England.We compared richness, abundance and composition of pollinating insects (hymenopterans and syrphids) and insect‐pollinated plant communities between open‐canopy pond systems subjected to either (i) long‐term regular management of woody vegetation or (ii) recent restoration by woody vegetation and sediment removal with those communities at (iii) ponds dominated by woody vegetation.Canopy management increased the richness and abundance of pollinators and insect‐pollinated plants. Pollinator richness and abundance was best explained by improvements in flower resources at open‐canopy ponds. Management most strongly influenced hymenopteran communities.Ponds represent important semi‐natural habitats for insect‐pollinated plant and pollinator communities in farmland. To enhance food resources, diversity and abundance of diurnal pollinators, conservation management at ponds should aim for mosaics of ponds at different successional stages with a high proportion of early successional open‐canopy ponds. Agricultural ponds are emerging as important habitats not only for aquatic biodiversity, but also for terrestrial species, thus warranting their prioritisation in future agri‐environment schemes. [ABSTRACT FROM AUTHOR]

Purpose: Obesity is an established risk factor for venous thromboembolism (VTE), while studies on physical inactivity and VTE risk show conflicting results. We examined whether physical activity modified the association between obesity and VTE. Patients and Methods: We conducted a population-based cohort study by combining data on outcome diagnoses, comorbidities and medication from nationwide registries with self-reported lifestyle data from an extensive Danish lifestyle questionnaire (2001– 2015). We computed incidence rates (IRs) and hazard ratios (HRs) of VTE for categories of body mass index (BMI), among the total study population (n=57,523) and for physically active (n=25,387) and inactive individuals (n=30,902) separately. Results: Obesity (BMI ≥ 30 kg/m2) was as expected associated with increased VTE risk compared with normal weight (HR 1.62, 95% confidence interval (CI): 1.26– 2.09). Independent of BMI category, the rate of VTE was higher for inactive than active individuals. Thus, among obese individuals, the IR per 1000 person-years was 2.03 (95% CI: 1.60– 2.57) for inactive and 1.44 (95% CI: 0.97– 2.15) for active individuals. In contrast, the HR for VTE comparing obese with normal weight individuals were higher for active (HR 2.19, 95% CI: 1.35– 3.58) than inactive individuals (HR 1.36, 95% CI: 1.00– 1.84). Conclusion: Physical activity acts as an effect measure modifier of the association between obesity and VTE. Thus, physical activity reduced the absolute rate of VTE among obese individuals but increased the relative rate of VTE among obese compared with normal weight individuals. [ABSTRACT FROM AUTHOR]

The coexistence of coronary artery disease (CAD) and chronic kidney disease (CKD) implies overlapped genetic foundation. However, the common genetic determination between the two diseases remains largely unknown. Relying on summary statistics publicly available from large scale genome-wide association studies (n = 184,305 for CAD and n = 567,460 for CKD), we observed significant positive genetic correlation between CAD and CKD (r g = 0.173, p = 0.024) via the linkage disequilibrium score regression. Next, we implemented gene-based association analysis for each disease through MAGMA (Multi-marker Analysis of GenoMic Annotation) and detected 763 and 827 genes associated with CAD or CKD (FDR < 0.05). Among those 72 genes were shared between the two diseases. Furthermore, by integrating the overlapped genetic information between CAD and CKD, we implemented two pleiotropy-informed informatics approaches including cFDR (conditional false discovery rate) and GPA (Genetic analysis incorporating Pleiotropy and Annotation), and identified 169 and 504 shared genes (FDR < 0.05), of which 121 genes were simultaneously discovered by cFDR and GPA. Importantly, we found 11 potentially new pleiotropic genes related to both CAD and CKD (i.e., ARHGEF19, RSG1, NDST2, CAMK2G, VCL, LRP10, RBM23, USP10, WNT9B, GOSR2 , and RPRML). Five of the newly identified pleiotropic genes were further repeated via an additional dataset CAD available from UK Biobank. Our functional enrichment analysis showed that those pleiotropic genes were enriched in diverse relevant pathway processes including quaternary ammonium group transmembrane transporter, dopamine transport. Overall, this study identifies common genetic architectures overlapped between CAD and CKD and will help to advance understanding of the molecular mechanisms underlying the comorbidity of the two diseases. [ABSTRACT FROM AUTHOR]

The inverse association between physical activity and arterial thrombotic disease is well established. Evidence on the association between physical activity and venous thromboembolism (VTE) is divergent. We conducted a systematic review and meta-analysis of published observational prospective cohort studies evaluating the associations of physical activity with VTE risk. MEDLINE, Embase, Web of Science, and manual search of relevant bibliographies were systematically searched until 26 February 2019. Extracted relative risks (RRs) with 95% confidence intervals (CIs) for the maximum versus minimal amount of physical activity groups were pooled using random effects meta-analysis. Twelve articles based on 14 unique prospective cohort studies comprising of 1,286,295 participants and 23,753 VTE events were eligible. The pooled fully-adjusted RR (95% CI) of VTE comparing the most physically active versus the least physically active groups was 0.87 (0.79–0.95). In pooled analysis of 10 studies (288,043 participants and 7069 VTE events) that reported risk estimates not adjusted for body mass index (BMI), the RR (95% CI) of VTE was 0.81 (0.70–0.93). The associations did not vary by geographical location, age, sex, BMI, and methodological quality of studies. There was no evidence of publication bias among contributing studies. Pooled observational prospective cohort studies support an association between regular physical activity and low incidence of VTE. The relationship does not appear to be mediated or confounded by BMI. [ABSTRACT FROM AUTHOR]

In June 2009 a small group of investigators met at the annual Movement Disorders Society meeting in Paris. The explicit goal of this meeting was to discuss a potential research alliance focused on the genetics of Parkinson disease (PD). The outcome of this informal meeting was the creation of the International Parkinson Disease Genomics Consortium (IPDGC), a group focused on collaborative genetics research, enabled by trust, sharing, and as little paperwork as possible. The IPDGC has grown considerably since its inception, including over 100 scientists from around the World. The focus has also grown, to include clinical and functional investigation of PD at scale. Most recently, the IPDGC has expanded to initiate major research efforts in East Asia and Africa, and has prioritized collaborations with ongoing major efforts in India and South America. Here we summarize the efforts of the IPDGC thus far and place these in the context of a decade of progress in PD genomics. We also discuss the future direction of IPDGC and our stated research priorities for the next decade. [ABSTRACT FROM AUTHOR]

Variable temperature photoluminescence of ZnO thin films deposited by a reactive laser ablation of metallic zinc was investigated. Free and bound exciton emissions are absent at cryogenic temperature, and the near band edge (NBE) emission is independent of measurement temperature for the ZnO thin film deposited at room temperature. Annealing at 700 °C results in the removal of defects, reappearance of exciton emission, and a temperature dependent NBE emission. The experimental data suggest that defects play an important role in the band edge emission in terms of both spectra shape and temperature dependence. Our observations will have an impact on device applications using ZnO, especially for optoelectronics that utilizes the exciton emission. [ABSTRACT FROM AUTHOR]

Compression molding of long fiber reinforced composites offers specific advantages in automotive applications due to the high strength to weight ratio, the comparably low tooling costs and short cycle times. However, the manufacturing process of long fiber composite parts presents a range of challenges. The phenomenon of fiber matrix separation (FMS) is causing severe deviations in fiber content, especially in complex ribbed structures. Currently, there is no commercial software that is capable to accurately predict FMS. This work uses a particle level mechanistic model to study FMS in a rib filling application. The direct fiber simulation (DFS) is uniquely suited to this application due to its ability to model individual fibers and their bending, as well as the interaction amongst fibers that leads to agglomeration. The effects of mold geometry, fiber length, viscosity, and initial fiber orientation are studied. It is shown that fiber length and initial fiber orientation have the most pronounced effects on fiber volume percentage in the ribs, with viscosity and part geometry playing a smaller role. [ABSTRACT FROM AUTHOR]

Recent studies have identified thousands of regions in the genome associated with chromatin modifications, which may in turn be affecting gene expression. Existing works have used heuristic methods to investigate the relationships between genome, epigenome, and gene expression, but, to our knowledge, none have explicitly modeled the chain of causality whereby genetic variants impact chromatin, which impacts gene expression. In this work we introduce a new hierarchical fine-mapping framework that integrates information across all three levels of data to better identify the causal variant and chromatin mark that are concordantly influencing gene expression. In simulations we show that our method is more accurate than existing approaches at identifying the causal mark influencing expression. We analyze empirical genetic, chromatin, and gene expression data from 65 African-ancestry and 47 European-ancestry individuals and show that many of the paths prioritized by our method are consistent with the proposed causal model and often lie in likely functional regions. [ABSTRACT FROM AUTHOR]

The objective of this study is to evaluate the biocompatibility of composite powder consisting of silica and titania (SiO2 –TiO2) for biomedical applications. The advancement of nanoscience and nanotechnology encourages researchers to actively participate in reinvention of existing materials with improved physical, chemical and biological properties. Hence, a composite/hybrid material has given birth of new materials with intriguing properties. In the present investigation, SiO2 –TiO2 composite powder was synthesised by sol‐gel method and the prepared nanocomposite was characterised for its phase purity, functional groups, surface topography by powder X‐ray diffraction (XRD), Fourier transform infrared spectroscopy (FT‐IR) and scanning electron microscopy. Furthermore, to understand the adverse effects of composite, biocompatibility test was analysed by cell culture method using MG63 osteoblast cell lines as a basic screening method. From the results, it was observed that typical Si–O–Ti peaks in FT‐IR confirms the formation of composite and the crystallinity of the composite powder was analysed by XRD analysis. Further in vitro biocompatibility and acridine orange results have indicated better biocompatibility at different concentrations on osteoblast cell lines. On the basis of these observations, we envision that the prepared silica–titania nanocomposite is an intriguing biomaterial for better biomedical applications. [ABSTRACT FROM AUTHOR]

β-Cryptoxanthin, a carotenoid found in fruits and vegetables such as tangerines, red peppers, and pumpkin, has several functions important for human health. Most evidence from observational, in vitro, animal model, and human studies suggests that β-Cryptoxanthin has relatively high bioavailability from its common food sources, to the extent that some β-Cryptoxanthin-rich foods might be equivalent to b-carotene-rich foods as sources of retinol. b-Cryptoxanthin is an antioxidant in vitro and appears to be associated with decreased risk of some cancers and degenerative diseases. In addition, many in vitro, animal model, and human studies suggest that β-Cryptoxanthin-rich foods may have an anabolic effect on bone and, thus, may help delay osteoporosis. [ABSTRACT FROM AUTHOR]

Herein we report a facile and economic method to prepare nanovoid Bi2WO6 2D ordered arrays employing a simple self-assembly procedure. The electrochemical properties and performance of the 2D nanoarray as a photoanode for water splitting are investigated and compared with a conventional photoanode of similar thickness. The 2D array photoanode shows a much higher photocurrent density and photon-to-H2 conversion efficiency even with a small content of the Bi2WO6 material. The enhancement is further studied and explained on the basis of the superiority of light scattering and photogenerated hole diffusion within the 2D array structure. This work provides a facile method to improve the efficiency of solar energy conversion systems by minimizing the charge-carrier diffusion length and reducing the light reflection, as well as reducing the amount of the semiconductor material (often costly and/or rare) present in the photoanode. [ABSTRACT FROM AUTHOR]

We investigated photoelectrodes based on TiO2–polyheptazine hybrid materials. Since both TiO2 and polyheptazine are extremely chemically stable, these materials are highly promising candidates for fabrication of photoanodes for water photooxidation. The properties of the hybrids were experimentally determined by a careful analysis of optical absorption spectra, luminescence properties and photoelectrochemical measurements, and corroborated by quantum chemical calculations. We provide for the first time clear experimental evidence for the formation of an interfacial charge-transfer complex between polyheptazine (donor) and TiO2 (acceptor), which is responsible for a significant red shift of absorption and photocurrent response of the hybrid as compared to both of the single components. The direct optical charge transfer from the HOMO of polyheptazine to the conduction band edge of TiO2 gives rise to an absorption band centered at 2.3 eV (540 nm). The estimated potential of photogenerated holes (+1.7 V vs. NHE, pH 7) allows for photooxidation of water (+0.82 V vs. NHE, pH 7) as evidenced by visible light-driven (λ ＞ 420 nm) evolution of dioxygen on hybrid electrodes modified with IrO2 nanoparticles as a co-catalyst. The quantum-chemical simulations demonstrate that the TiO2–polyheptazine interface is a complex and flexible system energetically favorable for proton-transfer processes required for water oxidation. Apart from water splitting, this type of hybrid materials may also find further applications in a broader research area of solar energy conversion and photo-responsive devices. [ABSTRACT FROM AUTHOR]

The article offers information on Denoising Algorithm based on Relevance network Topology (DART), an algorithm which improves molecular pathway activity inference. It states DART identifies a hypothesized association between oestrogen signalling and mammographic density in estrogen receptor positive (ER+) breast cancer. It states the denoising may substantially improve the subsequent inference of pathway activity in clinical tumor specimens.

Precisely synchronized neuronal activity has been commonly observed in the mammalian visual pathway. Spike timing correlations in the lateral geniculate nucleus (LGN) often take the form of phase synchronized oscillations in the high gamma frequency range. To study the relations between oscillatory activity, synchrony, and their time-dependent properties, we recorded activity from multiple single units in the cat LGN under stimulation by stationary spots of light. Autocorrelation analysis showed that approximately one third of the cells exhibited oscillatory firing with a mean frequency ~80 Hz. Cross-correlation analysis showed that 30% of unit pairs showed significant synchronization, and 61% of these pairs consisted of synchronous oscillations. Crosscorrelation analysis assumes that synchronous firing is stationary and maintained throughout the period of stimulation. We tested this assumption by applying unitary events analysis (UEA). We found that UEA was more sensitive to weak and transient synchrony than cross-correlation analysis and detected a higher incidence (49% of cell pairs) of significant synchrony (unitary events). In many unit pairs, the unitary events were optimally characterized at a bin width of 1 ms, indicating that neural synchrony has a high degree of temporal precision. We also found that approximately one half of the unit pairs showed nonstationary changes in synchrony that could not be predicted by the modulation of firing rates. Population statistics showed that the onset of synchrony between LGN cells occurred significantly later than that observed between retinal afferents and LGN cells. The synchrony detected among unit pairs recorded on separate tetrodes tended to be more transient and have a later onset than that observed between adjacent units. These findings show that stimulus-evoked synchronous activity within the LGN is often rhythmic, highly nonstationary, and modulated by endogenous processes that are not tightly correlated with firing rate. [ABSTRACT FROM AUTHOR]

The tether-assisted synthesis of [3]rotaxane by olefin metathesis has been studied in detail. Bis(crown ether)s, in which two crown ethers are connected by a linker, were threaded onto ammonium salts bearing a terminal olefin to form pseudorotaxanes. The pseudorotaxanes were converted into tethered rotaxanes in the presence of Grubbs catalyst, followed by removal of the linkers to produce [3]rotaxanes in excellent yields. Preorganisation of the two reactive ends has led to a great improvement in the yield of [3]rotaxanes. The ring strain of the tethered rotaxanes and the flexibility of the pseudorotaxanes were responsible for the formation of the tethered rotaxanes. [ABSTRACT FROM AUTHOR]

A list of books received by the journal "Conservation Biology" is presented including "Urban Acupuncture," by J. Lerner, "How to Do Ecology," by R. Karban, and "Hope on Conservation," by P. R. Ehrlich.

Simple Summary: Pancreatic cancer has been ranked seventh in the top ten cancer mortality rates for the past three year in Taiwan. It is one of the more difficult cancers to detect early due to the lack of early diagnostic tools. This is a population-based study from NHIRD. A higher performance pancreatic cancer prediction model has been established. This predictive model can improve the awareness of the risk of pancreatic cancer and give patients with pancreatic cancer a simpler tool for early screening in the golden period when the disease can still be eradicated. (1) Background: Cancer has been the leading cause of death in Taiwan for 39 years, and among them, pancreatic cancer has been ranked seventh in the top ten cancer mortality rates for the past three years. While the incidence rate of pancreatic cancer is ranked at the bottom of the top 10 cancers, the survival rate is very low. Pancreatic cancer is one of the more difficult cancers to detect early due to the lack of early diagnostic tools. Early screening is important for the treatment of pancreatic cancer. Only a few studies have designed predictive models for pancreatic cancer. (2) Methods: The Taiwan Health Insurance Database was used in this study, covering over 99% of the population in Taiwan. The subset sample was not significantly different from the original NHIRD sample. A machine learning approach was used to develop a predictive model for pancreatic cancer disease. Four models, including logistic regression, deep neural networks, ensemble learning, and voting ensemble were used in this study. The ROC curve and a confusion matrix were used to evaluate the accuracy of the pancreatic cancer prediction models. (3) Results: The AUC of the LR model was higher than the other three models in the external testing set for all three of the factor combinations. Sensitivity was best measured by the stacking model for the first factor combinations, and specificity was best measured by the DNN model for the second factor combination. The result of the model that used only nine factors (third factor combinations) was equal to the other two factor combinations. The AUC of the previous models for the early assessment of pancreatic cancer ranged from approximately 0.57 to 0.71. The AUC of this study was higher than that of previous studies and ranged from 0.71 to 0.76, which provides higher accuracy. (4) Conclusions: This study compared the performances of LR, DNN, stacking, and voting models for pancreatic cancer prediction and constructed a pancreatic cancer prediction model with accuracy higher than that of previous studies. This predictive model will improve awareness of the risk of pancreatic cancer and give patients with pancreatic cancer a simpler tool for early screening in the golden period when the disease can still be eradicated. [ABSTRACT FROM AUTHOR]

Zinc oxide (ZnO) nanoparticles functionalized with a bi-functional coupling agent methacryloxypropyl-trimethoxysilane (MPS) were used to fabricate a vinyl-ester resin polymeric nanocomposite, which shows an improved interfacial interaction between the particle and matrix. As a result, in comparison to the unmodified particle-filled nanocomposites, the functionalized particle-filled composites possessed higher resistance to thermal degradation, and demonstrated improved UV shielding and enhanced photoluminescent properties. The more uniform particle dispersion, passivation of the particle surface with MPS and increased oxygen vacancies were justified to contribute to the increased thermal stability and the enhanced photoluminescent properties. Significant tensile strength improvement was closely related to the observed uniform particle distribution and the intimate interfacial interaction through the strong chemical bonding. [ABSTRACT FROM AUTHOR]

YBCO dc superconducting quantum interference device (SQUID) magnetometers based on bicrystal junctions have been fabricated for magnetocardiograph measurements. The pickup coil of the device was designed employing 16 parallel loops with 50-μm-wide lines. Noise performance was improved by applying a modification in the coupling line between pickup loop and SQUID washer. We could obtain optimized SQUID magnetometer design having magnetic field noise of about 38 fT/Hz1/2 at 1 Hz and about 20 fT/Hz1/2 at 100 Hz with an 1/f corner frequency of 2 Hz, measured inside a magnetically-Shielded room. Demonstration of magnetocardiograph measurements showed quite promising results with high signal-to-noise ratio of 82 with a moderate magnetic shielding. [ABSTRACT FROM AUTHOR]

BackgroundA retina implant for restoring basic visual perception in patients who are blind due to photoreceptor loss should not only evoke focal phosphenes at high resolution, but should also generate cortical representations of form and motion. We are currently exploring these potential capabilities in anaesthetised cats.MethodsFibre electrodes were inserted through a small scleral incision onto the retinal surface for stimulation. For the recording of cortical population activities we placed up to 16 fibre electrodes in areas 17 and/or 18. Retinal and cortical electrodes were adjusted to corresponding sites, i.e., overlapping receptive fields. Electrical stimuli were charge-balanced impulses (200 µs, 10?100 µA). Basic form stimuli were generated by the selective and synchronous activation of some of the seven retinal stimulation electrodes. Movement stimuli were generated by spatio-temporal shifting of form stimuli. From multiple microelectrode recordings we computed stimulus-related spatio-temporal cortical activation profiles. We used these profiles to estimate the relations between stimulation distance and spatial resolution (form) and between stimulus velocity and spatio-temporal resolution (movement). Influences by the retino-cortical pathway were assessed by comparing cortical activations evoked by true form or motion stimuli with synthetic responses composed by superpositioning of responses to appropriate subsets of form and motion stimuli. In addition, we compared cortical responses to form and motion stimuli by a receptive-field-based backprojection of cortical activities.ResultsWe confirmed our previous finding that electrical retina stimulation may yield a spatial resolution of 1?5° visual angle and a temporal resolution of about 20 ms. We found that the spatio-temporal cortical activation profiles are commonly related to retinal form and motion stimuli. Cortical activity analyses showed that for two-point form stimuli the neuronal interaction depends on the stimulation electrodes'' distance and that local cortical group activities can exhibit some tuning to the directions or the velocities of moving electrical bars''. Projections of cortical activations to visual space were consistent with electrical form and motion stimulation of the retina.ConclusionsOur data indicate that retinal stimulation with electrical form and motion stimuli can lead to spatio-temporally related cortical activations. However, the selective activation of single cortical neurones with specific visual tuning properties by electrical retina stimulation and the potential adaptation of the visual system to long-term stimulation with retina implants should be addressed in future work. [ABSTRACT FROM AUTHOR]

Single layer direct-coupled YBCO SQUID magnetometers have been fabricated and characterized for the purpose of MCG measurements in magnetically disturbed environment. Two types of magnetometers have been designed and fabricated using 10 mm × 10 mm substrates. We could operate the conventional 3-mm-wide solid pickup loop magnetometers more stably than the 12-parallel-line pickup loop magnetometers in laboratory environment. We developed a first-order electronic gradiometer system with the SQUID magnetometers with axial displacement of 80 mm without any mechanical alignment of magnetometers. The system with a software filter using calculation of discrete Fourier transform could record clear magnetocardiogram in a weak magnetic shield-room. [ABSTRACT FROM AUTHOR]

Presents information on a study that analyzed the resistivity and Hall coefficient of n- and p-type silicon with initial p from 10...-cm to 30K...-cm. Experimental procedure; Results and discussion.

Minimum onset latency (Lmin) of single- and multiple-unit responses were mapped in the primary auditory cortex (AI) of barbiturate-anesthetized cats. Contralateral Lmin for multiple units was non-homogeneously distributed along the dorso-ventral/isofrequency axis of the AI. Responses with shorter latencies were more often located in the central, more sharply tuned region while longer latencies were more frequently encountered in the dorsal and ventral portions of the AI. For single units, a large scatter of Lmin values was found throughout the extent of the AI including cortical depth. The relationship between Lmin and previously reported spectral, intensity and temporal parameters was analyzed and revealed statistically significant correlations between minimum onset latency and the following response properties in some but not all studied animals: sharpness of tuning of a frequency response area 10 dB above threshold, broadband transient response, strongest response level, monotonicity of rate/level functions, dynamic range, and preferred frequency modulation sweep direction. This analysis suggests that Lmin is determined by several independent factors and that the prediction of Lmin based on relationships with other spectral and temporal response properties is inherently weak. The spatial distribution and the functional relationship between these response parameters may provide an important aspect of the time-based cortical representation of specific features in the animal's natural environment. [ABSTRACT FROM AUTHOR]

Presents research which studied the shape of receptive fields in the primary visual cortex of cats. Adaptation of the visual system to environmental stimulus; Dynamic control of visual resolution; Response of individual cells in the visual cortex; Modifications in the visual cortex; Shrinking of cortical receptive fields.

Presents research which identified a nuclear-hormone-receptor homologue, SEX-1, that regulates the transcription of xol-1 in Caenorhabditis elegans. Molecular aspects of the X-chromosome counting mechanism; Role of X signal elements; Repression of xol-1; SEX-1 protein acting on xol-1 directly; Effects of a nuclear hormone receptor to determine nematode sex.

Abstract. This paper reports the development of a large-scale model of some spinal reflex circuitry, useful for studying the dynamic interactions among neuronal populations during simple behaviors. The included populations and properties of the neurons and terminals were derived from the literature, mainly on cat spinal cord. The model was conceived as a symmetrical controller of a pair of antagonistic muscles, within the behavioral domain of the stretch and Golgi-tendon-organ reflexes, and was scaled to include realistic numbers of motoneurons. Inputs to the model were fiber populations providing random synaptic drive to some of the populations and sensory stimuli appropriate for the reflexes. The resulting model contained roughly 2300 neurons in six pairs of populations. The total number of connections in the model was about 600000, and individual postsynaptic potentials were small (0.1-0.6 reV). Model responses were calibrated by examination of their ability to reproduce known aspects of the reflexes. Published algorithms were used to construct the environment, which is easily expandable, in terms of membrane channels, neuronal geometry, and synaptic properties. The system was built to combine a system-level perspective of spinal circuitry with the single-unit perspective common in electrophysiological investigation. It provides a computational tool for system-level investigations of spinal cord similar to the tools available at the level of membrane currents. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PCa) is associated with a poor prognosis and high mortality rate. The causes of PCa are not fully elucidated yet, although certain exposome factors have been identified. The exposome is defined as the sum of all environmental factors influencing the occurrence of a disease during a life span. The development of an exposome approach for PCa has the potential to discover new disease-associated factors to better understand the carcinogenesis of PCa and help with early detection strategies. Our systematic review of the literature identified several exposome factors that have been associated with PCa alone and in combination with other exposures. A potential inflammatory signature has been observed among the interaction of several exposures (i.e., smoking, alcohol consumption, diabetes mellitus, obesity, and inflammatory markers) that further increases the incidence and progression of PCa. A large number of exposures have been identified such as genetic, hormonal, microorganism infections and immune responses that warrant further investigation. Future early detection strategies should utilize this information to assess individuals' risk for PCa. [ABSTRACT FROM AUTHOR]

Background: Breast Cancer (BC) is associated with inherited gene mutations. High throughput genotyping of BC samples has led to the identification and characterization of biomarkers for the diagnosis of BC. The most common genetic variants studied are SNPs (Single Nucleotide Polymorphisms) that determine susceptibility to an array of diseases thus serving as a potential tool for identifying the underlying causes of breast carcinogenesis.Methods: SNP genotyping employing the Agena MassARRAY offers a robust, sensitive, cost-effective method to assess multiple SNPs and samples simultaneously. In this present study, we analyzed 15 SNPs of 14 genes in 550 samples (150 cases and 400 controls). We identified four SNPs of genes TCF21, SLC19A1, DCC, and ERCC1 showing significant association with BC in the population under study.Results: The SNPs were rs12190287 (TCF21) having OR 1.713 (1.08-2.716 at 95% CI) p-value 0.022 (dominant), rs1051266 (SLC19A1) having OR 3.461 (2.136-5.609 at 95% CI) p-value 0.000000466 (dominant), rs2229080 (DCC) having OR 0.6867 (0.5123-0.9205 at 95% CI) p-value 0.0116 (allelic) and rs2298881 (ERCC1) having OR 0.669 (0.46-0.973 at 95% CI), p-value 0.035 (additive) respectively. The in-silico analysis was further used to fortify the above findings.Conclusion: It is further anticipated that the variants should be evaluated in other population groups that may aid in understanding the genetic complexity and bridge the missing heritability. [ABSTRACT FROM AUTHOR]

Laboratory medicine in sports medicine is taking on an ever-greater role in the assessment and monitoring of an athlete's health condition. The acute or intense exercise practiced by elite athletes can lead to the appearance of infections, inflammations, muscle injuries or cardiovascular disorders, whose diagnosis is not always rapid and efficient, as there is no continuous monitoring of the athlete. The absence of such monitoring can have serious consequences in terms of recovery of the professional athlete. These imbalances can induce metabolic adaptations which translate into alterations of specific parameters in terms of concentration and activity. The aim of this study was to follow the variation of specific biochemical biomarkers in a basketball team participating to the maximum championship during different phases of the agonistic season. The evaluation of serum biomarkers can help doctors to safeguard the athlete's health and sports trainers to adapt workouts, thus avoiding the appearance of diseases and injuries that in some cases can be underestimated by becoming irreversible ailments that do not allow the athlete to return to a healthy state. This information can be useful to create athlete biologic passports. [ABSTRACT FROM AUTHOR]