Ruthenium polypyridyl peptide conjugates: membrane permeable probes for cellular imaging

Two novel polyarginine labelled ruthenium polypyridyl dyes are reported, one conjugated to five, (Ru-Ahx-R5), and one to eight arginine residues, (Ru-Ahx-R8). Both complexes exhibit long-lived, intense, and oxygen sensitive luminescence. (Ru-R8) is passively, efficiently and very rapidly transported across the cell membrane into the cytoplasm without requirement for premeablisation of the cell membrane. Such ruthenium polypyridyl peptide conjugates open up the possibility for targeted cell delivery for environmentally sensitive intensity and lifetime imaging

A Series of 15 Patients with Extracranial Carotid Artery Aneurysms: Surgical and Endovascular Treatment

AbstractObjectivesThis is a retrospective review of 15 patients with primary and secondary aneurysms of extracranial carotid arteries treated surgically and endoluminally over 20 years in one centre.Patients and methodsFifteen aneurysms of extracranial carotid arteries were noticed in the same number of patients: five atherosclerotic, two after previous carotid surgery, six post-traumatic, one inflammatory, one of unknown etiology. All of them were symptomatic.ResultsIn the group treated surgically some complications occurred in the perioperative time: one haematoma, two transient neurological deficits, one fatal stroke. In the endovascular group of patients no complications occurred after the treatment. One fatal stroke occurred during operation—the patient died on the 43rd postoperative day due to respiratory insufficiency. Two other deaths occurred during the follow-up: one caused by myocardial infarction 10 years after the aneurysm resection, and the second due to a fatal stroke 3 years after aneurysmorraphy. One patient refused treatment and died 9 months after being diagnosed.ConclusionNeurological deficits in patients after neck injuries should arouse the suspicion of the presence of a carotid artery aneurysm. Open repair remains the method of choice in treating carotid artery aneurysms but endovascular procedures create the possibility of treating extracranial aneurysms in selected cases when open surgery is not recommended

Characterization of the HeCo mutant mouse: a new model of subcortical band heterotopia associated with seizures and behavioral deficits.

In human, neuronal migration disorders are commonly associated with developmental delay, mental retardation, and epilepsy. We describe here a new mouse mutant that develops a heterotopic cortex (HeCo) lying in the dorsolateral hemispheric region, between the homotopic cortex (HoCo) and subcortical white matter. Cross-breeding demonstrated an autosomal recessive transmission. Birthdating studies and immunochemistry for layer-specific markers revealed that HeCo formation was due to a transit problem in the intermediate zone affecting both radially and tangentially migrating neurons. The scaffold of radial glial fibers, as well as the expression of doublecortin is not altered in the mutant. Neurons within the HeCo are generated at a late embryonic age (E18) and the superficial layers of the HoCo have a correspondingly lower cell density and layer thickness. Parvalbumin immunohistochemistry showed the presence of gamma-aminobutyric acidergic cells in the HeCo and the mutant mice have a lowered threshold for the induction of epileptic seizures. The mutant showed a developmental delay but, in contrast, memory function was relatively spared. Therefore, this unique mouse model resembles subcortical band heterotopia observed in human. This model represents a new and rare tool to better understand cortical development and to investigate future therapeutic strategies for refractory epilepsy

ECFA Detector R&D Panel, Review Report

Two special calorimeters are foreseen for the instrumentation of the very forward region of an ILC or CLIC detector; a luminometer (LumiCal) designed to measure the rate of low angle Bhabha scattering events with a precision better than 10$^{-3}$ at the ILC and 10$^{-2}$ at CLIC, and a low polar-angle calorimeter (BeamCal). The latter will be hit by a large amount of beamstrahlung remnants. The intensity and the spatial shape of these depositions will provide a fast luminosity estimate, as well as determination of beam parameters. The sensors of this calorimeter must be radiation-hard. Both devices will improve the e.m. hermeticity of the detector in the search for new particles. Finely segmented and very compact electromagnetic calorimeters will match these requirements. Due to the high occupancy, fast front-end electronics will be needed. Monte Carlo studies were performed to investigate the impact of beam-beam interactions and physics background processes on the luminosity measurement, and of beamstrahlung on the performance of BeamCal, as well as to optimise the design of both calorimeters. Dedicated sensors, front-end and ADC ASICs have been designed for the ILC and prototypes are available. Prototypes of sensor planes fully assembled with readout electronics have been studied in electron beams.Comment: 61 pages, 51 figure

Luminometer for the future International Linear Collider - simulation and beam test results

LumiCal will be the luminosity calorimeter for the proposed International Large Detector of the International Linear Collider (ILC). The ILC physics program requires the integrated luminosity to be measured with a relative precision on the order of 10e-3, or 10e-4 when running in GigaZ mode. Luminosity will be determined by counting Bhabha scattering events coincident in the two calorimeter modules placed symmetrically on opposite sides of the interaction point. To meet these goals, the energy resolution of the calorimeter must be better than 1.5% at high energies. LumiCal has been designed as a 30-layer sampling calorimeter with tungsten as the passive material and silicon as the active material. Monte Carlo simulation using the Geant4 software framework has been used to identify design elements which adversely impact energy resolution and correct for them without loss of statistics. BeamCal, covering polar angles smaller than LumiCal, will serve for beam tuning, luminosity optimisation and high energy electron detection. Secondly, prototypes of the sensors and electronics for both detectors have been evaluated during beam tests, the results of which are also presented here.Comment: Technology and Instrumentation in Particle Physics 2011, Chicago, IL, USA. Presented June 11, 2011, and submitted to Physics Procedi

Comparative proteomic profiling reveals mechanisms for early spinal cord vulnerability in CLN1 disease

CLN1 disease is a fatal inherited neurodegenerative lysosomal storage disease of early childhood, caused by mutations in the CLN1 gene, which encodes the enzyme Palmitoyl protein thioesterase-1 (PPT-1). We recently found significant spinal pathology in Ppt1-deficient (Ppt1−/−) mice and human CLN1 disease that contributes to clinical outcome and precedes the onset of brain pathology. Here, we quantified this spinal pathology at 3 and 7 months of age revealing significant and progressive glial activation and vulnerability of spinal interneurons. Tandem mass tagged proteomic analysis of the spinal cord of Ppt1−/−and control mice at these timepoints revealed a significant neuroimmune response and changes in mitochondrial function, cell-signalling pathways and developmental processes. Comparing proteomic changes in the spinal cord and cortex at 3 months revealed many similarly affected processes, except the inflammatory response. These proteomic and pathological data from this largely unexplored region of the CNS may help explain the limited success of previous brain-directed therapies. These data also fundamentally change our understanding of the progressive, site-specific nature of CLN1 disease pathogenesis, and highlight the importance of the neuroimmune response. This should greatly impact our approach to the timing and targeting of future therapeutic trials for this and similar disorders

Infrastructure for Detector Research and Development towards the International Linear Collider

The EUDET-project was launched to create an infrastructure for developing and testing new and advanced detector technologies to be used at a future linear collider. The aim was to make possible experimentation and analysis of data for institutes, which otherwise could not be realized due to lack of resources. The infrastructure comprised an analysis and software network, and instrumentation infrastructures for tracking detectors as well as for calorimetry.Comment: 54 pages, 48 picture

Electrophysiological dynamics of Chinese phonology during visual word recognition in Chinese-English bilinguals

Silent word reading leads to the activation of orthographic (spelling), meaning, as well as phonological (sound) information. For bilinguals, native language information can also be activated automatically when they read words in their second language. For example, when Chinese-English bilinguals read words in their second language (English), the phonology of the Chinese translations is automatically activated. Chinese phonology, however, consists of consonants and vowels (segmental) and tonal information. To what extent these two aspects of Chinese phonology are activated is yet unclear. Here, we used behavioural measures, event-related potentials and oscillatory EEG to investigate Chinese segmental and tonal activation during word recognition. Evidence of Chinese segmental activation was found when bilinguals read English words (faster responses, reduced N400, gamma-band power reduction) and when they read Chinese words (increased LPC, gamma-band power reduction). In contrast, evidence for Chinese tonal activation was only found when bilinguals read Chinese words (gamma-band power increase). Together, our converging behavioural and electrophysiological evidence indicates that Chinese segmental information is activated during English word reading, whereas both segmental and tonal information are activated during Chinese word reading. Importantly, gamma-band oscillations are modulated differently by tonal and segmental activation, suggesting independent processing of Chinese tones and segments

Does Sleep Improve Your Grammar? : Preferential Consolidation of Arbitrary Components of New Linguistic Knowledge

We examined the role of sleep-related memory consolidation processes in learning new form-meaning mappings. Specifically, we examined a Complementary Learning Systems account, which implies that sleep-related consolidation should be more beneficial for new hippocampally dependent arbitrary mappings (e.g. new vocabulary items) relative to new systematic mappings (e.g. grammatical regularities), which can be better encoded neocortically. The hypothesis was tested using a novel language with an artificial grammatical gender system. Stem-referent mappings implemented arbitrary aspects of the new language, and determiner/suffix+natural gender mappings implemented systematic aspects (e.g. tib scoiffesh + ballerina, tib mofeem + bride; ked jorool + cowboy, ked heefaff + priest). Importantly, the determiner-gender and the suffix-gender mappings varied in complexity and salience, thus providing a range of opportunities to detect beneficial effects of sleep for this type of mapping. Participants were trained on the new language using a word-picture matching task, and were tested after a 2-hour delay which included sleep or wakefulness. Participants in the sleep group outperformed participants in the wake group on tests assessing memory for the arbitrary aspects of the new mappings (individual vocabulary items), whereas we saw no evidence of a sleep benefit in any of the tests assessing memory for the systematic aspects of the new mappings: Participants in both groups extracted the salient determiner-natural gender mapping, but not the more complex suffix-natural gender mapping. The data support the predictions of the complementary systems account and highlight the importance of the arbitrariness/systematicity dimension in the consolidation process for declarative memories