FindSim: a Framework for Integrating Neuronal Data and Signaling Models

Current experiments touch only small but overlapping parts of very complex subcellular signaling networks in neurons. Even with modern optical reporters and pharmacological manipulations, a given experiment can only monitor and control a very small subset of the diverse, multiscale processes of neuronal signaling. We have developed FindSim (Framework for Integrating Neuronal Data and SIgnaling Models) to anchor models to structured experimental datasets. FindSim is a framework for integrating many individual electrophysiological and biochemical experiments with large, multiscale models so as to systematically refine and validate the model. We use a structured format for encoding the conditions of many standard physiological and pharmacological experiments, specifying which parts of the model are involved, and comparing experiment outcomes with model output. A database of such experiments is run against successive generations of composite cellular models to iteratively improve the model against each experiment, while retaining global model validity. We suggest that this toolchain provides a principled and scalable way to tackle model complexity and diversity of data sources

First Results from the ISO‐IRAS Faint Galaxy Survey

We present the first results from the ISO-IRAS Faint Galaxy Survey (IIFGS), a program designed to obtain ISO observations of the most distant and luminous galaxies in the IRAS Faint Source Survey by filling short gaps in the ISO observing schedule with pairs of 12 μm ISOCAM and 90 μm ISOPHOT observations. As of 1997 October, over 500 sources have been observed, with an ISOCAM detection rate over 80%, covering over 1.25 deg^2 of sky to an 11.5 μm point-source completeness limit of approximately 1.0 mJy (corresponding to a ~10 σ detection sensitivity). Observations are presented for nine sources detected by ISOPHOT and ISOCAM early in the survey for which we have ground-based G- and I-band images and optical spectroscopy. The ground-based data confirm that the IIFGS strategy efficiently detects moderate-redshift (z = 0.11-0.38 for this small sample) strong emission line galaxies with L_(60 μm) ≳ 10^(11) L_☉; one of our sample has L_(60 μm) > 10^(12) L_☉ (H_0 = 75 km s^(-1) Mpc^(-1), Ω = 1). The infrared-optical spectral energy distributions are comparable to those of nearby luminous infrared galaxies, which span the range from pure starburst (e.g., Arp 220) to infrared QSO (Mrk 231). Two of the systems show signs of strong interaction, and four show active galactic nucleus (AGN)-like excitation; one of the AGNs, F15390+6038, which shows a high excitation Seyfert 2 spectrum, has an unusually warm far- to mid-infrared color and may be an obscured QSO. The IIFGS sample is one of the largest and deepest samples of infrared-luminous galaxies available, promising to be a rich sample for studying infrared-luminous galaxies up to z ~ 1 and for understanding the evolution of infrared galaxies and the star formation rate in the universe

The ISO-IRAS Faint Galaxy Survey

The ISO-IRAS Faint Galaxy Survey will obtain comprehensive space- and ground-based observations of the most distant and luminous galaxies in the IRAS Faint Source Survey. ISO observations are obtained by filling short gaps in the ISO observing schedule with pairs of 11.5μm ISOCAM and 90μm ISOPHOT observations. As of the October 1997 date of this Conference, over 500 sources have been observed by ISO with an ISOCAM detection rate exceeding 803. Ground-based spectrophotometry confirms that the IIFGS efficiently detects moderateredshift, strong emission line Luminous Infrared Galaxies. Spectrophotometry is currently available for 67 galaxies with 0.07 < z < 0. 7 and L_(fir) > 10^(11) L_☉. The galaxies are comparable to nearby LIGs, showing HII/Liner excitation; about 10% exhibit strong AGN characteristics. As a part of this survey we will cover over 1.25 square degrees of sky to an 11.5μm limit of approximately l.0mJy, allowing a sensitive estimate of the 11.5μm logN-logS Relationship. Preliminary ll.5μm source counts suggest substantial evolution in the mid-infrared galaxy population

First Results from the ISO‐IRAS Faint Galaxy Survey

We present the first results from the ISO-IRAS Faint Galaxy Survey (IIFGS), a program designed to obtain ISO observations of the most distant and luminous galaxies in the IRAS Faint Source Survey by filling short gaps in the ISO observing schedule with pairs of 12 μm ISOCAM and 90 μm ISOPHOT observations. As of 1997 October, over 500 sources have been observed, with an ISOCAM detection rate over 80%, covering over 1.25 deg^2 of sky to an 11.5 μm point-source completeness limit of approximately 1.0 mJy (corresponding to a ~10 σ detection sensitivity). Observations are presented for nine sources detected by ISOPHOT and ISOCAM early in the survey for which we have ground-based G- and I-band images and optical spectroscopy. The ground-based data confirm that the IIFGS strategy efficiently detects moderate-redshift (z = 0.11-0.38 for this small sample) strong emission line galaxies with L_(60 μm) ≳ 10^(11) L_☉; one of our sample has L_(60 μm) > 10^(12) L_☉ (H_0 = 75 km s^(-1) Mpc^(-1), Ω = 1). The infrared-optical spectral energy distributions are comparable to those of nearby luminous infrared galaxies, which span the range from pure starburst (e.g., Arp 220) to infrared QSO (Mrk 231). Two of the systems show signs of strong interaction, and four show active galactic nucleus (AGN)-like excitation; one of the AGNs, F15390+6038, which shows a high excitation Seyfert 2 spectrum, has an unusually warm far- to mid-infrared color and may be an obscured QSO. The IIFGS sample is one of the largest and deepest samples of infrared-luminous galaxies available, promising to be a rich sample for studying infrared-luminous galaxies up to z ~ 1 and for understanding the evolution of infrared galaxies and the star formation rate in the universe

Neuropsychiatric risk in children with intellectual disability of genetic origin: IMAGINE, a UK national cohort study

Background Children with intellectual disability frequently have multiple co-morbid neuropsychiatric conditions and poor physical health. Genomic testing is increasingly recommended as a first-line investigation for these children. We aim to determine the effect of genomics, inheritance, and socioeconomic deprivation on neuropsychiatric risk in children with intellectual disability of genetic origin as compared with the general population. Methods IMAGINE is a prospective cohort study using online mental health and medical assessments in a cohort of 3407 UK participants with intellectual disability and pathogenic genomic variants as identified by the UK's National Health Service (NHS). Our study is on a subset of these participants, including all children aged 4–19 years. We collected diagnostic genomic reports from NHS records and asked primary caregivers to provide an assessment of their child using the Development and Well-Being Assessment (DAWBA), the Strengths and Difficulties Questionnaire (SDQ), the Adaptive Behaviour Assessment System 3 (ABAS-3), and a medical history questionnaire. Each child was assigned a rank based on their postcode using the index of multiple deprivation (IMD). We compared the IMAGINE cohort with the 2017 National Survey of Children's Mental Health in England. The main outcomes of interest were mental health and neurodevelopment according to the DAWBA and SDQ. Findings We recruited 2770 children from the IMAGINE study between Oct 1, 2014 and June 30, 2019, of whom 2397 (86·5%) had a basic assessment of their mental health completed by their families and 1277 (46·1%) completed a medical history questionnaire. The mean age of participants was 9·2 years (SD 3·9); 1339 (55·9%) were boys and 1058 (44·1%) were girls. 355 (27·8%) of 1277 reported a seizure disorder and 814 (63·7%) reported movement or co-ordination problems. 1771 (73·9%) of 2397 participants had a pathogenic copy number variant (CNV) and 626 (26·1%) had a pathogenic single nucleotide variant (SNV). Participants were representative of the socioeconomic spectrum of the UK general population. The relative risk (RR) of co-occurring neuropsychiatric diagnoses, compared with the English national population, was high: autism spectrum disorder RR 29·2 (95% CI 23·9–36·5), ADHD RR 13·5 (95% CI 11·1–16·3). In children with a CNV, those with a familial variant tended to live in more socioeconomically deprived areas than those with a de novo variant. Both inheritance and socioeconomic deprivation contributed to neuropsychiatric risk in those with a CNV. Interpretation Children with genomic variants and intellectual disability are at an increased risk of neuropsychiatric difficulties. CNV variant inheritance and socioeconomic deprivation also contribute to the risk. Early genomic investigations of children with intellectual disability could facilitate the identification of the most vulnerable children. Additionally, harnessing parental expertise using online DAWBA assessments could rapidly identify children with exceptional needs to child mental health services

FabSim: Facilitating computational research through automation on large-scale and distributed e-infrastructures

We present FabSim, a toolkit developed to simplify a range of computational tasks for researchers in diverse disciplines. FabSim is flexible, adaptable, and allows users to perform a wide range of tasks with ease. It also pro- vides a systematic way to automate the use of resourcess, including HPC and distributed resources, and to make tasks easier to repeat by recording contextual information. To demonstrate this, we present three use cases where FabSim has enhanced our research productivity. These include sim- ulating cerebrovascular bloodflow, modelling clay-polymer nanocomposites across multiple scales, and calculating ligand-protein binding affinities

Asymmetry in photoelectron emission from chiral molecules induced by circularly polarized light

Bowering N, Lischke T, Schmidtke B, Müller N, Khalil T, Heinzmann U. Asymmetry in photoelectron emission from chiral molecules induced by circularly polarized light. PHYSICAL REVIEW LETTERS. 2001;86(7):1187-1190.In photoionization of free, unoriented chiral molecules with circularly polarized radiation, a significant circular dichroism, i.e., an asymmetry in the forward-backward electron emission, has been observed in the photoelectron angular distribution. This leads also to an asymmetry in the momentum transfer to the photoions. The spectra for the left- and right-handed enantiomers of bromocamphor exhibit asymmetries up to several percent which vary as a function of orbital binding energy. This enantioselective: effect can similarly occur for biomolecules with handedness, like amino acids, and may thus be a contributing factor related to the origin of the terrestrial biomolecular homochirality