LSTM with Working Memory

Previous RNN architectures have largely been superseded by LSTM, or "Long Short-Term Memory". Since its introduction, there have been many variations on this simple design. However, it is still widely used and we are not aware of a gated-RNN architecture that outperforms LSTM in a broad sense while still being as simple and efficient. In this paper we propose a modified LSTM-like architecture. Our architecture is still simple and achieves better performance on the tasks that we tested on. We also introduce a new RNN performance benchmark that uses the handwritten digits and stresses several important network capabilities.Comment: Accepted at IJCNN 201

High-brightness organic light-emitting diodes for optogenetic control of Drosophila locomotor behaviour

We thank Simone Lenk and Tobias Günther (TU Dresden) for fruitful discussions and technical support with OLED preparation. We are grateful for financial support from the Scottish Funding Council (through SUPA), Human Frontier Science Program (RGY0074/2013), Wellcome Trust Institutional Strategic Support Fund St Andrews and the RS Macdonald Charitable Trust. C.M. acknowledges funding by the European Commission through a Marie Sklodowska-Curie Individual Fellowship (703387).Organic light emitting diodes (OLEDs) are in widespread use in today’s mobile phones and are likely to drive the next generation of large area displays and solid-state lighting. Here we show steps towards their utility as a platform technology for biophotonics, by demonstrating devices capable of optical controlling behaviour in live animals. Using devices with pin OLED architecture, sufficient illumination intensity (0.3 mW.mm-2) to activate channelrhodopsins (ChRs) in vivo was reliably achieved at low operating voltages (5 V). In Drosophila melanogaster third instar larvae expressing ChR2(H134R) in motor neurons, we found that pulsed illumination from blue and green OLEDs triggered robust and reversible contractions in animals. This response was temporally coupled to the timing of OLED illumination. With blue OLED illumination, the initial rate and overall size of the behavioural response was strongest. Green OLEDs achieved roughly 70% of the response observed with blue OLEDs. Orange OLEDs did not produce contractions in larvae, in agreement with the spectral response of ChR2(H134R). The device configuration presented here could be modified to accommodate other small model organisms, cell cultures or tissue slices and the ability of OLEDs to provide patterned illumination and spectral tuning can broaden their utility in optogenetics experiments further.Publisher PDFPeer reviewe

On Problems Dual to Unification: The String-Rewriting Case

In this paper, we investigate problems which are dual to the unification problem, namely the Fixed Point (FP) problem, Common Term (CT) problem and the Common Equation (CE) problem for string rewriting systems. Our main motivation is computing fixed points in systems, such as loop invariants in programming languages. We show that the fixed point (FP) problem is reducible to the common term problem. Our new results are: (i) the fixed point problem is undecidable for finite convergent string rewriting systems whereas it is decidable in polynomial time for finite, convergent and dwindling string rewriting systems, (ii) the common term problem is undecidable for the class of dwindling string rewriting systems, and (iii) for the class of finite, monadic and convergent systems, the common equation problem is decidable in polynomial time but for the class of dwindling string rewriting systems, common equation problem is undecidable.Comment: 28 pages, 6 figures, will be submitted for LMCS journal. arXiv admin note: substantial text overlap with arXiv:1706.0560

Organic light-emitting diodes for optogenetic stimulation of Drosophila larvae

We are grateful for financial support from the Scottish Funding Council (through SUPA), Human Frontier Science Program (RGY0074/2013), Wellcome Trust Institutional Strategic Support Fund St Andrews, the RS Macdonald Charitable Trust, and EPSRC via grant EP/J01771X/1. CM acknowledges funding by the European Commission through a Marie Skłodowska Curie individual fellowship (703387).Optogenetics is an emerging method in biology that enables controlling neurons with light. We use organic light-emitting diodes to stimulate neurons in Drosophila larvae and investigate subsequent behavioral changes at different light intensities.Postprin

Optical mapping of ground reaction force dynamics in freely behaving Drosophila melanogaster larvae

Funding: EPSRC (Doctoral Training grant EP/L505079/1 and grant EP/P030017/1), the European Research Council under the European Union’s Horizon 2020 Framework Programme (FP/2014-202) ERC grant agreement no. 640012 (ABLASE), and the Alexander von Humboldt Foundation via the Humboldt Professorship to MCGDuring locomotion, soft-bodied terrestrial animals solve complex control problems at substrate interfaces, but our understanding of how they achieve this without rigid components remains incomplete. Here, we develop new all-optical methods based on optical interference in a deformable substrate to measure ground reaction forces (GRFs) with micrometre and nanonewton precision in behaving Drosophila larvae. Combining this with a kinematic analysis of substrate-interfacing features, we shed new light onto the biomechanical control of larval locomotion. Crawling in larvae measuring ~1 mm in length involves an intricate pattern of cuticle sequestration and planting, producing GRFs of 1–7 µN. We show that larvae insert and expand denticulated, feet-like structures into substrates as they move, a process not previously observed in soft-bodied animals. These ‘protopodia’ form dynamic anchors to compensate counteracting forces. Our work provides a framework for future biomechanics research in soft-bodied animals and promises to inspire improved soft-robot design.Peer reviewe

Data-driven information retrieval in heterogeneous collections of transcriptomics data links SIM2s to malignant pleural mesothelioma

Motivation: Genome-wide measurement of transcript levels is an ubiquitous tool in biomedical research. As experimental data continues to be deposited in public databases, it is becoming important to develop search engines that enable the retrieval of relevant studies given a query study. While retrieval systems based on meta-data already exist, data-driven approaches that retrieve studies based on similarities in the expression data itself have a greater potential of uncovering novel biological insights

Rare coding variants in ten genes confer substantial risk for schizophrenia

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3-50, PPeer reviewe

Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects

Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (OR=1.11, P=5.7×10−15), which persisted after excluding loci implicated in previous studies (OR=1.07, P=1.7 ×10−6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 ×10−11) and neurobehavioral phenotypes in mouse (OR = 1.18, P= 7.3 ×10−5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by non-allelic homologous recombination

No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study

It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe