Release probability increases towards distal dendrites boosting high-frequency signal transfer in the rodent hippocampus

Dendritic integration of synaptic inputs involves their increased electrotonic attenuation at distal dendrites, which can be counterbalanced by the increased synaptic receptor density. However, during network activity the influence of individual synapses depends on their release fidelity, the dendritic distribution of which remains poorly understood. Here, we employed classical optical quantal analyses and a genetically encoded optical glutamate sensor in acute hippocampal slices of rats and mice to monitor release at CA3-CA1 synapses. We find that their release probability increases with greater distances from the soma. Similar-fidelity synapses tend to group together whereas release probability shows no trends regarding the branch ends. Simulations with a realistic CA1 pyramidal cell hosting stochastic synapses suggest that the observed trends boost signal transfer fidelity, particularly at higher input frequencies. Because high-frequency bursting has been associated with learning, the release probability pattern we have found may play a key role in memory trace formation

Coupled ocean-atmosphere modeling and predictions

Key aspects of the current state of the ability of global and regional climate models to represent dynamical processes and precipitation variations are summarized. Interannual, decadal, and globalwarming timescales, wherein the influence of the oceans is relevant and the potential for predictability is highest, are emphasized. Oceanic influences on climate occur throughout the ocean and extend over land to affect many types of climate variations, including monsoons, the El Niño Southern Oscillation, decadal oscillations, and the response to greenhouse gas emissions. The fundamental ideas of coupling between the ocean-atmosphere-land system are explained for these modes in both global and regional contexts. Global coupled climate models are needed to represent and understand the complicated processes involved and allow us to make predictions over land and sea. Regional coupled climate models are needed to enhance our interpretation of the fine-scale response. The mechanisms by which large-scale, low-frequency variations can influence shorter timescale variations and drive regionalscale effects are also discussed. In this light of these processes, the prospects for practical climate predictability are also presented.AJMwas supported by theNSFEarth System Modeling Program (OCE1419306) and the NOAA Climate Variability and Prediction Program (NA14OAR4310276). HS thanks the Office of Naval Research for support under N00014-15-1-2588. LPP was supported by “Advanced Studies in Medium and High Latitudes Oceanography” (CAPES 23038.004304/2014-28) and “National Institute of Science andTechnology of the Cryosphere” (CNPq/PROANTAR704222/2009). VM was supported by NOAA grant NA12OAR4310078. TGJ was supported by the U. S. Naval Research Laboratory 6.2 project “Fresh Water Balance in the Coupled Ocean-Atmosphere System” (BE-435-040-62435N-6777) YHT was supported by the MOST grant 106-2111-M-002-001, Taiwan

Knee complaints and consequences on work status; a 10-year follow-up survey among floor layers and graphic designers

<p>Abstract</p> <p>Background</p> <p>The purpose of the study was to examine if knee complaints among floor layers predict exclusion from the trade.</p> <p>Methods</p> <p>In 1994/95 self-reported data were obtained from a cohort of floor layers and graphic designers with and without knee straining work activities, respectively. At follow-up in 2005 the questionnaire survey was repeated. The study population consisted of 81 floor layers and 173 graphic designers who were presently working in their trades at baseline (1995). All participants were men aged 36–70 years in 2005.</p> <p>We computed the risk of losing gainful employment in the trade according to occurrence of knee complaints at baseline, using Cox proportional hazard regression adjusted for a number of potential confounding variables. Moreover, the crude and adjusted odds risk ratio for knee complaints according to status of employment in the trade were computed, using graphic designers as reference.</p> <p>Results</p> <p>A positive but non-significant association between knee complaints lasting more than 30 days the past 12 months and exclusion from the trade was found among floor layers (Hazard Ratio = 1.4, 95% CI = 0.6–3.5).</p> <p>The frequency of self-reported knee complaints was lower among floor layers presently at work in the trade in year 2005 (26.3%) compared with baseline in 1995 (41.1%), while the opposite tendency was seen among graphic designers (20.7% vs. 10.7%).</p> <p>Conclusion</p> <p>The study suggests that knee complaints are a risk factor for premature exclusion from a knee demanding trade. However, low power of the study precludes strong conclusions. The study also indicates a healthy worker effect among floor layers and a survivor effect among graphic designers.</p

Quantum memory for entangled two-mode squeezed states

A quantum memory for light is a key element for the realization of future quantum information networks. Requirements for a good quantum memory are (i) versatility (allowing a wide range of inputs) and (ii) true quantum coherence (preserving quantum information). Here we demonstrate such a quantum memory for states possessing Einstein-Podolsky-Rosen (EPR) entanglement. These multi-photon states are two-mode squeezed by 6.0 dB with a variable orientation of squeezing and displaced by a few vacuum units. This range encompasses typical input alphabets for a continuous variable quantum information protocol. The memory consists of two cells, one for each mode, filled with cesium atoms at room temperature with a memory time of about 1msec. The preservation of quantum coherence is rigorously proven by showing that the experimental memory fidelity 0.52(2) significantly exceeds the benchmark of 0.45 for the best possible classical memory for a range of displacements.Comment: main text 5 pages, supplementary information 3 page

Differences in smoking associated DNA methylation patterns in South Asians and Europeans

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.Background DNA methylation is strongly associated with smoking status at multiple sites across the genome. Studies have largely been restricted to European origin individuals yet the greatest increase in smoking is occurring in low income countries, such as the Indian subcontinent. We determined whether there are differences between South Asians and Europeans in smoking related loci, and if a smoking score, combining all smoking related DNA methylation scores, could differentiate smokers from non-smokers. Results Illumina HM450k BeadChip arrays were performed on 192 samples from the Southall And Brent REvisited (SABRE) cohort. Differential methylation in smokers was identified in 29 individual CpG sites at 18 unique loci. Interaction between smoking status and ethnic group was identified at the AHRR locus. Ethnic differences in DNA methylation were identified in non-smokers at two further loci, 6p21.33 and GNG12. With the exception of GFI1 and MYO1G these differences were largely unaffected by adjustment for cell composition. A smoking score based on methylation profile was constructed. Current smokers were identified with 100% sensitivity and 97% specificity in Europeans and with 80% sensitivity and 95% specificity in South Asians. Conclusions Differences in ethnic groups were identified in both single CpG sites and combined smoking score. The smoking score is a valuable tool for identification of true current smoking behaviour. Explanations for ethnic differences in DNA methylation in association with smoking may provide valuable clues to disease pathways.Wellcome Trust Enhancement grantMedical Research CouncilDiabetes UKthe British Heart Foundatio

I-TRAP: A method to identify transcriptional regulator activated promoters

BACKGROUND: The differential expression of virulence genes is often used by microbial pathogens in adapting to the environment of their host. The differential expression of such sets of genes can be regulated by RNA polymerase sigma factors. Some sigma factors are differentially expressed, which can provide a means to identifying other differentially expressed genes such as those whose expression are controlled by the sigma factor. METHODS: To identify sigma factor-regulated genes, we developed a method, termed I-TRAP, for the identification of transcriptional regulator activated promoters. The I-TRAP method is based on the fact that some genes will be differentially expressed in the presence and absence of a transcriptional regulator. I-TRAP uses a DNA library in a promoter-trap vector that contains two reporter genes, one to allow the selection of active promoters in the presence of the transcriptional regulator and a second to allow screening for promoter activity in the absence of the transcriptional regulator. RESULTS: To illustrate the development and use of the I-TRAP approach, the construction of the vectors, host strains, and library necessary to identify SigmaE-regulated genes of Mycobacterium tuberculosis is described. CONCLUSION: The I-TRAP method should be a versatile and useful method for identifying and characterizing promoter activity under a variety of conditions and in response to various regulatory proteins. In our study, we isolated 360 clones that may contain plasmids carrying SigmaE-regulated promoters genes of M. tuberculosis

Diagnosis, prevalence estimation and burden measurement in population surveys of headache: presenting the HARDSHIP questionnaire

The global burden of headache is very large, but knowledge of it is far from complete and needs still to be gathered. Published population-based studies have used variable methodology, which has influenced findings and made comparisons difficult. The Global Campaign against Headache is undertaking initiatives to improve and standardize methods in use for cross-sectional studies. One requirement is for a survey instrument with proven cross-cultural validity. This report describes the development of such an instrument. Two of the authors developed the initial version, which was used with adaptations in population-based studies in China, Ethiopia, India, Nepal, Pakistan, Russia, Saudi Arabia, Zambia and 10 countries in the European Union. The resultant evolution of this instrument was reviewed by an expert consensus group drawn from all world regions. The final output was the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire, designed for application by trained lay interviewers. HARDSHIP is a modular instrument incorporating demographic enquiry, diagnostic questions based on ICHD-3 beta criteria, and enquiries into each of the following as components of headache-attributed burden: symptom burden; health-care utilization; disability and productive time losses; impact on education, career and earnings; perception of control; interictal burden; overall individual burden; effects on relationships and family dynamics; effects on others, including household partner and children; quality of life; wellbeing; obesity as a comorbidity. HARDSHIP already has demonstrated validity and acceptability in multiple languages and cultures. Modules may be included or not, and others (eg, on additional comorbidities) added, according to the purpose of the study and resources (especially time) available

Investor heterogeneity and the cross-section of U.K. investment trust performance

We use the upper and lower bounds derived by Ferson and Lin (2010) to examine the impact of investor heterogeneity on the performance of U.K. investment trusts relative to alternative linear factor models. We find using the upper bounds that investor heterogeneity has an important impact for nearly all investment trusts. The upper bounds are large in economic terms and significantly different from zero. We find no evidence of any trusts where all investors agree on the sign of performance beyond what we expect by chance. Using the lower bound, we find that trusts with a larger disagreement about trust performance have a weaker relation between the trust premium and past Net Asset Value (NAV) performance

Electronic Sensors for Assessing Interactions between Healthcare Workers and Patients under Airborne Precautions

International audienceBackground: Direct observation has been widely used to assess interactions between healthcare workers (HCWs) and patients but is time-consuming and feasible only over short periods. We used a Radio Frequency Identification Device (RFID) system to automatically measure HCW-patient interactions. Methods: We equipped 50 patient rooms with fixed sensors and 111 HCW volunteers with mobile sensors in two clinical wards of two hospitals. For 3 months, we recorded all interactions between HCWs and 54 patients under airborne precautions for suspected (n=40) or confirmed (n=14) tuberculosis. Number and duration of HCW entries into patient rooms were collected daily. Concomitantly, we directly observed room entries and interviewed HCWs to evaluate their self- perception of the number and duration of contacts with tuberculosis patients. Results: After signal reconstruction, 5490 interactions were recorded between 82 HCWs and 54 tuberculosis patients during 404 days of airborne isolation. Median (interquartile range) interaction duration was 2.1 (0.8-4.4) min overall, 2.3 (0.8-5.0) in the mornings, 1.8 (0.8-3.7) in the afternoons, and 2.0 (0.7-4.3) at night (P,1024). Number of interactions/day/HCW was 3.0 (1.0-6.0) and total daily duration was 7.6 (2.4-22.5) min. Durations estimated from 28 direct observations and 26 interviews were not significantly different from those recorded by the network. Conclusions: The RFID was well accepted by HCWs. This original technique holds promise for accurately and continuously measuring interactions between HCWs and patients, as a less resource-consuming substitute for direct observation. The results could be used to model the transmission of significant pathogens. HCW perceptions of interactions with patients accurately reflected reality

Tumor markers in breast cancer - European Group on Tumor Markers recommendations

Recommendations are presented for the routine clinical use of serum and tissue-based markers in the diagnosis and management of patients with breast cancer. Their low sensitivity and specificity preclude the use of serum markers such as the MUC-1 mucin glycoproteins ( CA 15.3, BR 27.29) and carcinoembryonic antigen in the diagnosis of early breast cancer. However, serial measurement of these markers can result in the early detection of recurrent disease as well as indicate the efficacy of therapy. Of the tissue-based markers, measurement of estrogen and progesterone receptors is mandatory in the selection of patients for treatment with hormone therapy, while HER-2 is essential in selecting patients with advanced breast cancer for treatment with Herceptin ( trastuzumab). Urokinase plasminogen activator and plasminogen activator inhibitor 1 are recently validated prognostic markers for lymph node-negative breast cancer patients and thus may be of value in selecting node-negative patients that do not require adjuvant chemotherapy. Copyright (C) 2005 S. Karger AG, Basel