Crossovers between epigenesis and epigenetics. A multicenter approach to the history of epigenetics (1901-1975)

The origin of epigenetics has been traditionally traced back to Conrad Hal Waddington's foundational work in 1940s. The aim of the present paper is to reveal a hidden history of epigenetics, by means of a multicenter approach. Our analysis shows that genetics and embryology in early XX century--far from being non-communicating vessels--shared similar questions, as epitomized by Thomas Hunt Morgan's works. Such questions were rooted in the theory of epigenesis and set the scene for the development of epigenetics. Since the 1950s, the contribution of key scientists (Mary Lyon and Eduardo Scarano), as well as the discussions at the international conference of Gif-sur-Yvette (1957) paved the way for three fundamental shifts of focus: 1. From the whole embryo to the gene; 2. From the gene to the complex extranuclear processes of development; 3. From cytoplasmic inheritance to the epigenetics mechanisms

Recursive Motion and Structure Estimation with Complete Error Characterization

We present an algorithm that perfom recursive estimation of ego-motion andambient structure from a stream of monocular Perspective images of a number of feature points. The algorithm is based on an Extended Kalman Filter (EKF) that integrates over time the instantaneous motion and structure measurements computed by a 2-perspective-views step. Key features of our filter are (I) global observability of the model, (2) complete on-line characterization of the uncertainty of the measurements provided by the two-views step. The filter is thus guaranteed to be well-behaved regardless of the particular motion undergone by the observel: Regions of motion space that do not allow recovery of structure (e.g. pure rotation) may be crossed while maintaining good estimates of structure and motion; whenever reliable measurements are available they are exploited. The algorithm works well for arbitrary motions with minimal smoothness assumptions and no ad hoc tuning. Simulations are presented that illustrate these characteristics

High-speed data transfer with FPGAs and QSFP+ modules

We present test results and characterization of a data transmission system based on a last generation FPGA and a commercial QSFP+ (Quad Small Form Pluggable +) module. QSFP+ standard defines a hot-pluggable transceiver available in copper or optical cable assemblies for an aggregated bandwidth of up to 40 Gbps. We implemented a complete testbench based on a commercial development card mounting an Altera Stratix IV FPGA with 24 serial transceivers at 8.5 Gbps, together with a custom mezzanine hosting three QSFP+ modules. We present test results and signal integrity measurements up to an aggregated bandwidth of 12 Gbps.Comment: 5 pages, 3 figures, Published on JINST Journal of Instrumentation proceedings of Topical Workshop on Electronics for Particle Physics 2010, 20-24 September 2010, Aachen, Germany(R Ammendola et al 2010 JINST 5 C12019

Synthesis, molecular modeling and biological evaluation of two new chicoric acid analogs

Two conformationally constrained compounds similar to chicoric acid but lacking the catechol and carboxyl groups were prepared. In these analogues, the single bond between the two caffeoyl fragments has been replaced with a chiral oxirane ring and both aromatic residues modified protecting completely or partially the catechol moiety as methyl ether. Preliminary molecular modelling studies carried out on the two analogues showed interactions near the active site of HIV integrase; however, in comparison with raltegravir, the biological evaluation confirmed that CAA-1 and CAA-2 were unable to inhibit infection at lower concentration

GPU-based Real-time Triggering in the NA62 Experiment

Over the last few years the GPGPU (General-Purpose computing on Graphics Processing Units) paradigm represented a remarkable development in the world of computing. Computing for High-Energy Physics is no exception: several works have demonstrated the effectiveness of the integration of GPU-based systems in high level trigger of different experiments. On the other hand the use of GPUs in the low level trigger systems, characterized by stringent real-time constraints, such as tight time budget and high throughput, poses several challenges. In this paper we focus on the low level trigger in the CERN NA62 experiment, investigating the use of real-time computing on GPUs in this synchronous system. Our approach aimed at harvesting the GPU computing power to build in real-time refined physics-related trigger primitives for the RICH detector, as the the knowledge of Cerenkov rings parameters allows to build stringent conditions for data selection at trigger level. Latencies of all components of the trigger chain have been analyzed, pointing out that networking is the most critical one. To keep the latency of data transfer task under control, we devised NaNet, an FPGA-based PCIe Network Interface Card (NIC) with GPUDirect capabilities. For the processing task, we developed specific multiple ring trigger algorithms to leverage the parallel architecture of GPUs and increase the processing throughput to keep up with the high event rate. Results obtained during the first months of 2016 NA62 run are presented and discussed

Hypoxia-induced nitric oxide production and tumour perfusion is inhibited by pegylated arginine deiminase (ADI-PEG20).

The hypoxic tumour microenvironment represents an aggressive, therapy-resistant compartment. As arginine is required for specific hypoxia-induced processes, we hypothesised that arginine-deprivation therapy may be useful in targeting hypoxic cancer cells. We explored the effects of the arginine-degrading agent ADI-PEG20 on hypoxia-inducible factor (HIF) activation, the hypoxia-induced nitric oxide (NO) pathway and proliferation using HCT116 and UMUC3 cells and xenografts. The latter lack argininosuccinate synthetase (ASS1) making them auxotrophic for arginine. In HCT116 cells, ADI-PEG20 inhibited hypoxic-activation of HIF-1α and HIF-2α, leading to decreased inducible-nitric oxide synthase (iNOS), NO-production, and VEGF. Interestingly, combining hypoxia and ADI-PEG20 synergistically inhibited ASS1. ADI-PEG20 inhibited mTORC1 and activated the unfolded protein response providing a mechanism for inhibition of HIF and ASS1. ADI-PEG20 inhibited tumour growth, impaired hypoxia-associated NO-production, and decreased vascular perfusion. Expression of HIF-1α/HIF-2α/iNOS and VEGF were reduced, despite an increased hypoxic tumour fraction. Similar effects were observed in UMUC3 xenografts. In summary, ADI-PEG20 inhibits HIF-activated processes in two tumour models with widely different arginine biology. Thus, ADI-PEG20 may be useful in the clinic to target therapy-resistant hypoxic cells in ASS1-proficient tumours and ASS1-deficient tumours.Thanks to Dr John Bomalaski, (Polaris Pharmaceuticals, Inc) for supplying the ADI-PEG20, to Dr Simon S Hoer for useful discussions and to members of Histopathology/ISH (CRUK Cambridge Institute, UK) for IHC and imaging assistance. This work was supported by the Wellcome Trust and the NIHR Cambridge Biomedical Research Centre Senior Investigator Awards (to P.H.M., supporting N.B.), EU FP7 Metoxia Grant agreement no. 222741 (to P.H.M., supporting G.C.), UCL Cancer Research UK Centre (to M.R.), King’s College London and UCL Comprehensive Cancer Imaging Centre, Cancer Research UK and EPSRC in association with the Medical Research Council (MRC), the DoH (England: to R.B.P.), MRC Cancer Unit Core Funding (to C.F., supporting E.G.).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/srep2295

NaNet: a Low-Latency, Real-Time, Multi-Standard Network Interface Card with GPUDirect Features

While the GPGPU paradigm is widely recognized as an effective approach to high performance computing, its adoption in low-latency, real-time systems is still in its early stages. Although GPUs typically show deterministic behaviour in terms of latency in executing computational kernels as soon as data is available in their internal memories, assessment of real-time features of a standard GPGPU system needs careful characterization of all subsystems along data stream path. The networking subsystem results in being the most critical one in terms of absolute value and fluctuations of its response latency. Our envisioned solution to this issue is NaNet, a FPGA-based PCIe Network Interface Card (NIC) design featuring a configurable and extensible set of network channels with direct access through GPUDirect to NVIDIA Fermi/Kepler GPU memories. NaNet design currently supports both standard - GbE (1000BASE-T) and 10GbE (10Base-R) - and custom - 34~Gbps APElink and 2.5~Gbps deterministic latency KM3link - channels, but its modularity allows for a straightforward inclusion of other link technologies. To avoid host OS intervention on data stream and remove a possible source of jitter, the design includes a network/transport layer offload module with cycle-accurate, upper-bound latency, supporting UDP, KM3link Time Division Multiplexing and APElink protocols. After NaNet architecture description and its latency/bandwidth characterization for all supported links, two real world use cases will be presented: the GPU-based low level trigger for the RICH detector in the NA62 experiment at CERN and the on-/off-shore data link for KM3 underwater neutrino telescope