Clinical review of retinotopy

Two observations made 29 years apart are the cornerstones of this review on the contributions of Dr Gordon T. Plant to understanding pathology affecting the optic nerve. The first observation laid the anatomical basis in 1990 for the interpretation of optical coherence tomography (OCT) findings in 2009. Retinal OCT offers clinicians detailed in vivo structural imaging of individual retinal layers. This has led to novel observations which were impossible to make using ophthalmoscopy. The technique also helps to re-introduce the anatomically grounded concept of retinotopy to clinical practise. This review employs illustrations of the anatomical basis for retinotopy through detailed translational histological studies and multimodal brain-eye imaging studies. The paths of the prelaminar and postlaminar axons forming the optic nerve and their postsynaptic path from the dorsal lateral geniculate nucleus to the primary visual cortex in humans are described. With the mapped neuroanatomy in mind we use OCT-MRI pairings to discuss the patterns of neurodegeneration in eye and brain that are a consequence of the hard wired retinotopy: anterograde and retrograde axonal degeneration which can, within the visual system, propagate trans-synaptically. The technical advances of OCT and MRI for the first time enable us to trace axonal degeneration through the entire visual system at spectacular resolution. In conclusion, the neuroanatomical insights provided by the combination of OCT and MRI allows us to separate incidental findings from sinister pathology and provides new opportunities to tailor and monitor novel neuroprotective strategies

90m Optics Studies and Operation in the LHC

ISBN 978-3-95450-115-1 - http://accelconf.web.cern.ch/AccelConf/IPAC2012/papers/moppc006.pdfInternational audienceA high β* = 90 m optics was commissioned and used for first very forward physics operation in the LHC in 2011. The experience gained from working with this optics in 5 studies and operation periods in 2011 was very positive. The target β* = 90 m was reached by a de-squeeze from the standard 11 m injection and ramp optics on the first attempt and collisions and first physics results obtained in the second study. The optics was measured and corrected with good precision. The running conditions were very clean and allowed for measurements with roman pots very close to the beam

The Cholangiocyte Glycocalyx Stabilizes the 'Biliary HCO3 Umbrella': An Integrated Line of Defense against Toxic Bile Acids

BACKGROUND Destruction of cholangiocytes is the hallmark of chronic cholangiopathies such as primary biliary cirrhosis. Under physiologic conditions, cholangiocytes display a striking resistance to the high, millimolar concentrations of toxic bile salts present in bile. We recently showed that a 'biliary HCO3(-) umbrella', i.e. apical cholangiocellular HCO3(-) secretion, prevents cholangiotoxicity of bile acids, and speculated on a role for extracellular membrane-bound glycans in the stabilization of this protective layer. This paper summarizes published and thus far unpublished evidence supporting the role of the glycocalyx in stabilizing the 'biliary HCO3(-) umbrella' and thus preventing cholangiotoxicity of bile acids. KEY MESSAGES The apical glycocalyx of a human cholangiocyte cell line and mouse liver sections were visualized by electron microscopy. FACS analysis was used to characterize the surface glycan profile of cultured human cholangiocytes. Using enzymatic digestion with neuraminidase the cholangiocyte glycocalyx was desialylated to test its protective function. Using lectin assays, we demonstrated that the main N-glycans in human and mouse cholangiocytes were sialylated biantennary structures, accompanied by high expression of the H-antigen (\textgreeka1-2 fucose). Apical neuraminidase treatment induced desialylation without affecting cell viability, but lowered cholangiocellular resistance to bile acid-induced toxicity: both glycochenodeoxycholate and chenodeoxycholate (pKa \geq4), but not taurochenodeoxycholate (pKa \textless2), displayed cholangiotoxic effects after desialylation. A 24-hour reconstitution period allowed cholangiocytes to recover to a pretreatment bile salt susceptibility pattern. CONCLUSION Experimental evidence indicates that an apical cholangiocyte glycocalyx with glycosylated mucins and other glycan-bearing membrane glycoproteins stabilizes the 'biliary HCO3(-) umbrella', thus aiding in the protection of human cholangiocytes against bile acid toxicity

Drosophila Hsc70-4 Is Critical for Neurotransmitter Exocytosis In Vivo

AbstractPrevious in vitro studies of cysteine-string protein (CSP) imply a potential role for the clathrin-uncoating ATPase Hsc70 in exocytosis. We show that hypomorphic mutations in Drosophila Hsc70-4 (Hsc4) impair nerve-evoked neurotransmitter release, but not synaptic vesicle recycling in vivo. The loss of release can be restored by increasing external or internal Ca2+ and is caused by a reduced Ca2+ sensitivity of exocytosis downstream of Ca2+ entry. Hsc4 and CSP are likely to act in common pathways, as indicated by their in vitro protein interaction, the similar loss of evoked release in individual and double mutants, and genetic interactions causing a loss of release in trans-heterozygous hsc4-csp double mutants. We suggest that Hsc4 and CSP cooperatively augment the probability of release by increasing the Ca2+ sensitivity of vesicle fusion

THE CNGS FACILITY: PERFORMANCE AND OPERATIONAL EXPERIENCE

The CNGS facility (CERN Neutrinos to Gran Sasso) aims at directly detecting muon to tau neutrino oscillations. An intense muon-neutrino beam (1E17 muon neutrinos/day) is generated at CERN and directed over 732 km towards the Gran Sasso National Laboratory, LNGS, in Italy, where two large and complex detectors, OPERA and ICARUS, are located. CNGS is the first long-baseline neutrino facility in which the measurement of the oscillation parameters is performed by observation of tau-neutrino appearance. In this paper, an overview of the CNGS facility is presented. The experience gained in operating this 500 kW neutrino beam facility is described. Major events since the commissioning of the facility in 2006 are summarized. Highlights on CNGS beam performance since the start of physics run in 2008 are given

Biliary Bicarbonate Secretion Constitutes a Protective Mechanism against Bile Acid-Induced Injury in Man

Background: Cholangiocytes expose a striking resistance against bile acids: while other cell types, such as hepatocytes, are susceptible to bile acid-induced toxicity and apoptosis already at micromolar concentrations, cholangiocytes are continuously exposed to millimolar concentrations as present in bile. We present a hypothesis suggesting that biliary secretion of HCO(3)(-) in man serves to protect cholangiocytes against bile acid-induced damage by fostering the deprotonation of apolar bile acids to more polar bile salts. Here, we tested if bile acid-induced toxicity is pH-dependent and if anion exchanger 2 (AE2) protects against bile acid-induced damage. Methods: A human cholangiocyte cell line was exposed to chenodeoxycholate (CDC), or its glycine conjugate, from 0.5 mM to 2.0 mM at pH 7.4, 7.1, 6.7 or 6.4, or after knockdown of AE2. Cell viability and apoptosis were determined by WST and caspase-3/-7 assays, respectively. Results: Glycochenodeoxycholate (GCDC) uptake in cholangiocytes is pH-dependent. Furthermore, CDC and GCDC (pK(a) 4-5) induce cholangiocyte toxicity in a pH-dependent manner: 0.5 mM CDC and 1 mM GCDC at pH 7.4 had no effect on cell viability, but at pH 6.4 decreased viability by >80% and increased caspase activity almost 10- and 30-fold, respectively. Acidification alone had no effect. AE2 knockdown led to 3- and 2-fold enhanced apoptosis induced by 0.75 mM CDC or 2 mM GCDC at pH 7.4. Discussion: These data support our hypothesis of a biliary HCO(3)(-) umbrella serving to protect human cholangiocytes against bile acid-induced injury. AE2 is a key contributor to this protective mechanism. The development and progression of cholangiopathies, such as primary biliary cirrhosis, may be a consequence of genetic and acquired functional defects of genes involved in maintaining the biliary HCO(3)(-) umbrella. Copyright (C) 2011 S. Karger AG, Base

Quantum interferences and gates with emitter-based coherent photon sources

Quantum emitters, such as atoms, defects in crystals, or quantum dots, are excellent sources of indistinguishable single-photons for quantum technologies. Upon coherent excitation, however, the emitted photonic state includes a vacuum component in a quantum superposition with the one-photon component. This feature has so far been largely disregarded in the framework of linear optical computing. Here we experimentally and theoretically study how the presence of photon-number coherence alters the foundation of photon-photon gates: the Hong-Ou-Mandel interference. We show that the presence of vacuum coherence not only introduces errors to standard photon indistinguishability measurements, but also results in complex quantum interference phenomena. These phenomena lead to additional entanglement that has profound impact on linear computing schemes, as we illustrate by simulating a heralded gate. Our work reveals the rich physics arising from photon-number coherence, which holds the potential to become an asset in future quantum protocols.Comment: 15 pages, 8 figure

Effectiveness of a family-centered method for the early identification of social-emotional and behavioral problems in children: a quasi experimental study

Background: Social-emotional and behavioral problems are common in childhood. Early identification of these is important as it can lead to interventions which may improve the child's prognosis. In Dutch Preventive Child Healthcare (PCH), a new family-centered method has been implemented to identify these problems in early childhood. Its main features are consideration of the child's developmental context and empowerment of parents to enhance the developmental context. Methods/design: In a quasi-experimental study, embedded in routine PCH in the Netherlands, regions in which the family-centered method has been implemented (intervention condition) will be compared to "care as usual" regions (control condition). These regions are comparable in regard to socio-demographic characteristics. From more than 3,500 newborn babies, 18-month follow-up data on social-emotional and behavioral development will be obtained. PCH professionals will assess development during each routine well-child visit; participating parents will fill in standardized questionnaires. Primary outcomes in the study are the proportion of social-emotional and behavioral problems identified by PCH professionals in children aged 2-14 and 18 months in both conditions, and the proportion of agreement between the assessment of PCH professionals and parents. In addition, the added value of the family-centered approach will be assessed by comparing PCH findings with standardized questionnaires. The secondary outcomes are the degree to which the needs of parents are met and the degree to which they are willing to disclose concerns. Discussion: The family-centered method seems promising for early identification of social-emotional and behavioral problems. The results of this study will contribute to evidence-based public health. Trial registration: NTR2681

Determination of a time-shift in the OPERA set-up using high energy horizontal muons in the LVD and OPERA detectors

The purpose of this work is to report the measurement of a time-shift in the OPERA set-up in a totally independent way from Time Of Flight (TOF) measurements of CNGS neutrino events. The LVD and OPERA experiments are both installed in the same laboratory: LNGS. The relative position of the two detectors, separated by an average distance of ~ 160 m, allows the use of very high energy horizontal muons to cross-calibrate the timing systems of the two detectors, using a TOF technique which is totally independent from TOF of CNGS neutrino events. Indeed, the OPERA-LVD direction lies along the so-called "Teramo anomaly", a region in the Gran Sasso massif where LVD has established, many years ago, the existence of an anomaly in the mountain structure, which exhibits a low m. w. e. thickness for horizontal directions. The "abundant" high-energy horizontal muons (nearly 100 per year) going through LVD and OPERA exist because of this anomaly in the mountain orography. The total live time of the data in coincidence correspond to 1200 days from mid 2007 until March 2012. The time coincidence study of LVD and OPERA detectors is based on 306 cosmic horizontal muon events and shows the existence of a negative time shift in the OPERA set-up of the order of deltaT(AB) = - (73 \pm 9) ns when two calendar periods, A and B, are compared. This result shows a systematic effect in the OPERA timing system from August 2008 until December 2011. The size of the effect is comparable with the neutrino velocity excess recently measured by OPERA. It is probably interesting not to forget that with the MRPC technology developed by the ALICE Bologna group the TOF world record accuracy of 20 ps was reached. That technology can be implemented at LNGS for a high precision determination of TOF with the CNGS neutrino beams of an order of magnitude smaller than the value of the OPERA systematic effect