Interactome comparison of human embryonic stem cell lines with the inner cell mass and trophectoderm

Networks of interacting co-regulated genes distinguish the inner cell mass (ICM) from the differentiated trophectoderm (TE) in the preimplantation blastocyst, in a species specific manner. In mouse the ground state pluripotency of the ICM appears to be maintained in murine embryonic stem cells (ESCs) derived from the ICM. This is not the case for human ESCs. In order to gain insight into this phenomenon, we have used quantitative network analysis to identify how similar human (h)ESCs are to the human ICM. Using the hESC lines MAN1, HUES3 and HUES7 we have shown that all have only a limited overlap with ICM specific gene expression, but that this overlap is enriched for network properties that correspond to key aspects of function including transcription factor activity and the hierarchy of network modules. These analyses provide an important framework which highlights the developmental origins of hESCs

Dialogue Act Modeling for Automatic Tagging and Recognition of Conversational Speech

We describe a statistical approach for modeling dialogue acts in conversational speech, i.e., speech-act-like units such as Statement, Question, Backchannel, Agreement, Disagreement, and Apology. Our model detects and predicts dialogue acts based on lexical, collocational, and prosodic cues, as well as on the discourse coherence of the dialogue act sequence. The dialogue model is based on treating the discourse structure of a conversation as a hidden Markov model and the individual dialogue acts as observations emanating from the model states. Constraints on the likely sequence of dialogue acts are modeled via a dialogue act n-gram. The statistical dialogue grammar is combined with word n-grams, decision trees, and neural networks modeling the idiosyncratic lexical and prosodic manifestations of each dialogue act. We develop a probabilistic integration of speech recognition with dialogue modeling, to improve both speech recognition and dialogue act classification accuracy. Models are trained and evaluated using a large hand-labeled database of 1,155 conversations from the Switchboard corpus of spontaneous human-to-human telephone speech. We achieved good dialogue act labeling accuracy (65% based on errorful, automatically recognized words and prosody, and 71% based on word transcripts, compared to a chance baseline accuracy of 35% and human accuracy of 84%) and a small reduction in word recognition error.Comment: 35 pages, 5 figures. Changes in copy editing (note title spelling changed

Sensitivities of a Standard Test Method for the Determination of the pHe of Bioethanol and Suggestions for Improvement

An assessment of the sensitivities of the critical parameters in the ASTM D6423 documentary standard method for the measurement of pHe in (bio)ethanol has been undertaken. Repeatability of measurements made using the same glass electrode and reproducibility between different glass electrodes have been identified as the main contributors to the uncertainty of the values produced. Strategies to reduce the uncertainty of the measurement have been identified and tested. Both increasing the time after which the pHe measurement is made following immersion in the sample, and rinsing the glass electrode with ethanol prior to immersion in the sample, have been shown to be effective in reducing the uncertainty of the numerical value produced. However, it is acknowledged that the values produced using these modified approaches may not be directly compared with those obtained using the documentary ASTM method since pHe is defined operationally by the process used to measure it

BRAF V600E-Positive Multisite Langerhans Cell Histiocytosis in a Preterm Neonate

Hemorrhagic pustules with a “blueberry muffin” appearance accompanied by respiratory failure in a neonate present a challenging differential diagnosis that includes infections and neoplasms. We present a case of multiorgan, multisite Langerhans cell histiocytosis (LCH), positive for the oncogenic BRAF V600E mutation, in a preterm neonate. Infants with LCH pose a diagnostic challenge due to their heterogeneous presentations. This case is unusual in that the newborn presented with severe multiorgan involvement. Due to the rare incidence, wide spectrum of clinical manifestations, and high mortality rate, clinicians must maintain a high index of suspicion for LCH

Hachimoji DNA and RNA: A genetic system with eight building blocks

Reported here are DNA and RNA-like systems built from eight (hachi-) nucleotide letters (-moji) that form four orthogonal pairs. This synthetic genetic biopolymer meets the structural requirements needed to support Darwinism, including a polyelectrolyte backbone, predictable thermodynamic stability, and stereoregular building blocks that fit a Schrödinger aperiodic crystal. Measured thermodynamic parameters predict the stability of hachimoji duplexes, allowing hachimoji DNA to double the information density of natural terran DNA. Three crystal structures show that the synthetic building blocks do not perturb the aperiodic crystal seen in the DNA double helix. Hachimoji DNA was then transcribed to give hachimoji RNA in the form of a functioning fluorescent hachimoji aptamer. These results expand the scope of molecular structures that might support life, including life throughout the cosmos

Patient-specific iPSC model of a genetic vascular dementia syndrome reveals failure of mural cells to stabilize capillary structures

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is the most common form of genetic stroke and vascular dementia syndrome resulting from mutations in NOTCH3. To elucidate molecular mechanisms of the condition and identify drug targets, we established a patient-specific induced pluripotent stem cell (iPSC) model and demonstrated for the first time a failure of the patient iPSC-derived vascular mural cells (iPSC-MCs) in engaging and stabilizing endothelial capillary structures. The patient iPSC-MCs had reduced platelet-derived growth factor receptor β, decreased secretion of the angiogenic factor vascular endothelial growth factor (VEGF), were highly susceptible to apoptotic insults, and could induce apoptosis of adjacent endothelial cells. Supplementation of VEGF significantly rescued the capillary destabilization. Small interfering RNA knockdown of NOTCH3 in iPSC-MCs revealed a gain-of-function mechanism for the mutant NOTCH3. These disease mechanisms likely delay brain repair after stroke in CADASIL, contributing to the brain hypoperfusion and dementia in this condition, and will help to identify potential drug targets

Evaluating eHealth: Undertaking Robust International Cross-Cultural eHealth Research

David Bates and Adam Wright discuss the opportunities and challenges of undertaking international collaborations in eHealth evaluation research, and make recommendations for moving forward

Twisted k-graph algebras associated to Bratteli diagrams

Given a system of coverings of k-graphs, we show that the cohomology of the resulting (k+1)-graph is isomorphic to that of any one of the k-graphs in the system. We then consider Bratteli diagrams of 2-graphs whose twisted C*-algebras are matrix algebras over noncommutative tori. For such systems we calculate the ordered K-theory and the gauge-invariant semifinite traces of the resulting 3-graph C*-algebras. We deduce that every simple C*-algebra of this form is Morita equivalent to the C*-algebra of a rank-2 Bratteli diagram in the sense of Pask-Raeburn-R{\o}rdam-Sims.Comment: 28 pages, pictures prepared using tik

Garden and landscape-scale correlates of moths of differing conservation status: significant effects of urbanization and habitat diversity

Moths are abundant and ubiquitous in vegetated terrestrial environments and are pollinators, important herbivores of wild plants, and food for birds, bats and rodents. In recent years, many once abundant and widespread species have shown sharp declines that have been cited by some as indicative of a widespread insect biodiversity crisis. Likely causes of these declines include agricultural intensification, light pollution, climate change, and urbanization; however, the real underlying cause(s) is still open to conjecture. We used data collected from the citizen science Garden Moth Scheme (GMS) to explore the spatial association between the abundance of 195 widespread British species of moth, and garden habitat and landscape features, to see if spatial habitat and landscape associations varied for species of differing conservation status. We found that associations with habitat and landscape composition were species-specific, but that there were consistent trends in species richness and total moth abundance. Gardens with more diverse and extensive microhabitats were associated with higher species richness and moth abundance; gardens near to the coast were associated with higher richness and moth abundance; and gardens in more urbanized locations were associated with lower species richness and moth abundance. The same trends were also found for species classified as increasing, declining and vulnerable under IUCN (World Conservation Union) criteria

Xanthus: Push-button Orchestration of Host Provenance Data Collection

Host-based anomaly detectors generate alarms by inspecting audit logs for suspicious behavior. Unfortunately, evaluating these anomaly detectors is hard. There are few high-quality, publicly-available audit logs, and there are no pre-existing frameworks that enable push-button creation of realistic system traces. To make trace generation easier, we created Xanthus, an automated tool that orchestrates virtual machines to generate realistic audit logs. Using Xanthus' simple management interface, administrators select a base VM image, configure a particular tracing framework to use within that VM, and define post-launch scripts that collect and save trace data. Once data collection is finished, Xanthus creates a self-describing archive, which contains the VM, its configuration parameters, and the collected trace data. We demonstrate that Xanthus hides many of the tedious (yet subtle) orchestration tasks that humans often get wrong; Xanthus avoids mistakes that lead to non-replicable experiments.Comment: 6 pages, 1 figure, 7 listings, 1 table, worksho