Programmable active memories in real-time tasks: implementing data-driven triggers for LHC experiments

The future Large Hadron Collider (LHC), to be built at CERN, presents among other technological challenges a formidable problem of real-time data analysis. At a primary event rate of 40 MHz, a multi-stage trigger system has to analyze data to decide which is the fraction of events that should be preserved on permanent storage for further analysis. We report on implementations of local algorithms for feature extraction as part of triggering, using the detectors of the proposed ATLAS experiment as a model. The algorithms were implemented for a decision frequency of 100 kHz, on different data-driven programmable devices based on structures of field- programmable gate arrays and memories. The implementations were demonstrated at full speed with emulated input, and were also integrated into a prototype detector running in a test beam at CERN, in June 1994

To respond or not to respond - a personal perspective of intestinal tolerance

For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research

Stereoselective Synthesis of (-)-Spicigerolide

(-)-Spicigerolide was enantioselectively synthesized from a protected (S)-lactaldehyde. The synthesis of the polyacetylated framework relied on two Zn-mediated stereoselective additions of alkynes to aldehydes as well as a regiocontrolled [3,3]-sigmatropic rearrangement of an allylic acetate. The pyranone moiety was constructed via ring-closing metathesis

Does visual cortex lactate increase following photic stimulation in migraine without aura patients? A functional 1H-MRS study

Proton magnetic resonance spectroscopy (1H-MRS) has been used in a number of studies to assess noninvasively the temporal changes of lactate (Lac) in the activated human brain. Migraine neurobiology involves lack of cortical habituation to repetitive stimuli and a mitochondrial component has been put forward. Our group has recently demonstrated a reduction in the high-energy phosphates adenosine triphosphate (ATP) and phosphocreatine (PCr) in the occipital lobe of migraine without aura (MwoA) patients, at least in a subgroup, in a phosphorus MRS (31P-MRS) study. In previous studies, basal Lac levels or photic stimulation (PS)-induced Lac levels were found to be increased in patients with migraine with aura (MwA) and migraine patients with visual symptoms and paraesthesia, paresia and/or dysphasia, respectively. The aim of this study was to perform functional 1H-MRS at 3 T in 20 MwoA patients and 20 control subjects. Repetitive visual stimulation was applied using MR-compatible goggles with 8 Hz checkerboard stimulation during 12 min. We did not observe any significant differences in signal integrals, ratios and absolute metabolite concentrations, including Lac, between MwoA patients and controls before PS. Lac also did not increase significantly during and following PS, both for MwoA patients and controls. Subtle Lac changes, smaller than the sensitivity threshold (i.e. estimated at 0.1–0.2 μmol/g at 3 T), cannot be detected by MRS. Our study does, however, argue against a significant switch to non-aerobic glucose metabolism during long-lasting PS of the visual cortex in MwoA patients

Extra-Visual Functional and Structural Connection Abnormalities in Leber's Hereditary Optic Neuropathy

We assessed abnormalities within the principal brain resting state networks (RSNs) in patients with Leber's hereditary optic neuropathy (LHON) to define whether functional abnormalities in this disease are limited to the visual system or, conversely, tend to be more diffuse. We also defined the structural substrates of fMRI changes using a connectivity-based analysis of diffusion tensor (DT) MRI data. Neuro-ophthalmologic assessment, DT MRI and RS fMRI data were acquired from 13 LHON patients and 13 healthy controls. RS fMRI data were analyzed using independent component analysis and SPM5. A DT MRI connectivity-based parcellation analysis was performed using the primary visual and auditory cortices, bilaterally, as seed regions. Compared to controls, LHON patients had a significant increase of RS fluctuations in the primary visual and auditory cortices, bilaterally. They also showed decreased RS fluctuations in the right lateral occipital cortex and right temporal occipital fusiform cortex. Abnormalities of RS fluctuations were correlated significantly with retinal damage and disease duration. The DT MRI connectivity-based parcellation identified a higher number of clusters in the right auditory cortex in LHON vs. controls. Differences of cluster-centroid profiles were found between the two groups for all the four seeds analyzed. For three of these areas, a correspondence was found between abnormalities of functional and structural connectivities. These results suggest that functional and structural abnormalities extend beyond the visual network in LHON patients. Such abnormalities also involve the auditory network, thus corroborating the notion of a cross-modal plasticity between these sensory modalities in patients with severe visual deficits

Neurexins and Neuroligins: Recent Insights from Invertebrates

During brain development, each neuron must find and synapse with the correct pre- and postsynaptic partners. The complexity of these connections and the relatively large distances some neurons must send their axons to find the correct partners makes studying brain development one of the most challenging, and yet fascinating disciplines in biology. Furthermore, once the initial connections have been made, the neurons constantly remodel their dendritic and axonal arbours in response to changing demands. Neurexin and neuroligin are two cell adhesion molecules identified as important regulators of this process. The importance of these genes in the development and modulation of synaptic connectivity is emphasised by the observation that mutations in these genes in humans have been associated with cognitive disorders such as Autism spectrum disorders, Tourette syndrome and Schizophrenia. The present review will discuss recent advances in our understanding of the role of these genes in synaptic development and modulation, and in particular, we will focus on recent work in invertebrate models, and how these results relate to studies in mammals