Microarray analyses demonstrate the involvement of type i interferons in psoriasiform pathology development in D6-deficient mice

The inflammatory response is normally limited by mechanisms regulating its resolution. In the absence of resolution, inflammatory pathologies can emerge, resulting in substantial morbidity and mortality. We have been studying the D6 chemokine scavenging receptor, which played an indispensable role in the resolution phase of inflammatory responses and does so by facilitating removal of inflammatory CC chemokines. In D6-deficient mice, otherwise innocuous cutaneous inflammatory stimuli induce a grossly exaggerated inflammatory response that bears many similarities to human psoriasis. In the present study, we have used transcriptomic approaches to define the molecular make up of this response. The data presented highlight potential roles for a number of cytokines in initiating and maintaining the psoriasis-like pathology. Most compellingly, we provide data indicating a key role for the type I interferon pathway in the emergence of this pathology. Neutralizing antibodies to type I interferons are able to ameliorate the psoriasis-like pathology, confirming a role in its development. Comparison of transcriptional data generated from this mouse model with equivalent data obtained from human psoriasis further demonstrates the strong similarities between the experimental and clinical systems. As such, the transcriptional data obtained in this preclinical model provide insights into the cytokine network active in exaggerated inflammatory responses and offer an excellent tool to evaluate the efficacy of compounds designed to therapeutically interfere with inflammatory processes

Controlled single electron transfer between Si:P dots

We demonstrate electrical control of Si:P double dots in which the potential is defined by nanoscale phosphorus doped regions. Each dot contains approximately 600 phosphorus atoms and has a diameter close to 30 nm. On application of a differential bias across the dots, electron transfer is observed, using single electron transistors in both dc- and rf-mode as charge detectors. With the possibility to scale the dots down to few and even single atoms these results open the way to a new class of precision-doped quantum dots in silicon.Comment: 3 figures, 3 page

Hydrodynamic object recognition using pressure sensing

Hydrodynamic sensing is instrumental to fish and some amphibians. It also represents, for underwater vehicles, an alternative way of sensing the fluid environment when visual and acoustic sensing are limited. To assess the effectiveness of hydrodynamic sensing and gain insight into its capabilities and limitations, we investigated the forward and inverse problem of detection and identification, using the hydrodynamic pressure in the neighbourhood, of a stationary obstacle described using a general shape representation. Based on conformal mapping and a general normalization procedure, our obstacle representation accounts for all specific features of progressive perceptual hydrodynamic imaging reported experimentally. Size, location and shape are encoded separately. The shape representation rests upon an asymptotic series which embodies the progressive character of hydrodynamic imaging through pressure sensing. A dynamic filtering method is used to invert noisy nonlinear pressure signals for the shape parameters. The results highlight the dependence of the sensitivity of hydrodynamic sensing not only on the relative distance to the disturbance but also its bearing

Hyperparameter Importance Across Datasets

With the advent of automated machine learning, automated hyperparameter optimization methods are by now routinely used in data mining. However, this progress is not yet matched by equal progress on automatic analyses that yield information beyond performance-optimizing hyperparameter settings. In this work, we aim to answer the following two questions: Given an algorithm, what are generally its most important hyperparameters, and what are typically good values for these? We present methodology and a framework to answer these questions based on meta-learning across many datasets. We apply this methodology using the experimental meta-data available on OpenML to determine the most important hyperparameters of support vector machines, random forests and Adaboost, and to infer priors for all their hyperparameters. The results, obtained fully automatically, provide a quantitative basis to focus efforts in both manual algorithm design and in automated hyperparameter optimization. The conducted experiments confirm that the hyperparameters selected by the proposed method are indeed the most important ones and that the obtained priors also lead to statistically significant improvements in hyperparameter optimization.Comment: \c{opyright} 2018. Copyright is held by the owner/author(s). Publication rights licensed to ACM. This is the author's version of the work. It is posted here for your personal use, not for redistribution. The definitive Version of Record was published in Proceedings of the 24th ACM SIGKDD International Conference on Knowledge Discovery & Data Minin

Maternal first trimester serum levels of free-beta human chorionic gonadotropin and male genital

Are maternal first trimester levels of serum free-beta hCG associated with the development of hypospadias or undescended testis (UDT) in boys? Overall, first trimester maternal levels of serum free-beta hCG are not associated with hypospadias or UDT. However, elevated levels were found in severe phenotypes (proximal hypospadias and bilateral UDT) suggesting an altered pathway of hormonal release in early pregnancy

Charge-based silicon quantum computer architectures using controlled single-ion implantation

We report a nanofabrication, control and measurement scheme for charge-based silicon quantum computing which utilises a new technique of controlled single ion implantation. Each qubit consists of two phosphorus dopant atoms ~50 nm apart, one of which is singly ionized. The lowest two energy states of the remaining electron form the logical states. Surface electrodes control the qubit using voltage pulses and dual single electron transistors operating near the quantum limit provide fast readout with spurious signal rejection. A low energy (keV) ion beam is used to implant the phosphorus atoms in high-purity Si. Single atom control during the implantation is achieved by monitoring on-chip detector electrodes, integrated within the device structure, while positional accuracy is provided by a nanomachined resist mask. We describe a construction process for implanted single atom and atom cluster devices with all components registered to better than 20 nm, together with electrical characterisation of the readout circuitry. We also discuss universal one- and two-qubit gate operations for this architecture, providing a possible path towards quantum computing in silicon.Comment: 9 pages, 5 figure

A new liver perfusion and preservation system for transplantation Research in large animals

A kidney perfusion machine, model MOX-100 (Waters Instruments, Ltd, Rochester, MN) was modified to allow continuous perfusion of the portal vein and pulsatile perfusion of the hepatic artery of the liver. Additional apparatus consists of a cooling system, a membrane oxygenator, a filter for foreign bodies, and bubble traps. This system not only allows hypothermic perfusion preservation of the liver graft, but furthermore enables investigation of ex vivo simulation of various circulatory circumstances in which physiological perfusion of the liver is studied. We have used this system to evaluate the viability of liver allografts preserved by cold storage. The liver was placed on the perfusion system and perfused with blood with a hematocrit of approximately 20% and maintained at 37°C for 3 h. The flows of the hepatic artery and portal vein were adjusted to 0.33 mL and 0.67 mL/g of liver tissue, respectively. Parameters of viability consisted of hourly bile output, oxygen consumption, liver enzymes, electrolytes, vascular resistance, and liver histology. This method of liver assessment in large animals will allow the objective evaluation of organ viability for transplantation and thereby improve the outcome of organ transplantation. Furthermore, this pump enables investigation into the pathophysiology of liver ischemia and preservation. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted