Operations aspects of the Fermilab Central Helium Liquefier facility

The Fermilab Central Helium Liquefier (CHL) facility consists of helium and nitrogen reliquefier plants operated 24 hours-a-day to supply LHe at 4.6 K and LN{sub 2} for the Fermilab Tevatron superconducting proton-antiproton collider ring and to recover warm return gases. Operating aspects of CHL, including different equipment and systems reliability, availability, maintenance experience, safety concerns, and economics aspects are discussed

MENTORING: DE UN SOPORTE VIRTUAL A UN PROYECTO INSTITUCIONAL

ResumenComo resultado de un trabajo de diagnosis de necesidades emerge la posibilidad de desarrollar un espacio virtual que incluya material didáctico-pedagógico como soporte de una asignatura en el ámbito universitario: Mentoring. Supone una ayuda importante para que los alumnos organicen de manera autónoma su estudio, avancen en los contenidos recorriendo sus propios caminos mediante un proceso individual de construcción y elaboración del conocimiento. Pudiendo además, consultar el plan docente, las normativas de cátedra, orientaciones didácticas, clases dictadas, actividades de nivelación y trabajos complementariospropuestos por el mentor. Mentoring propicia la comunicación (sincrónica y asincrónica) entre mentores y estudiantes potenciando tareas cooperativas en la realización de proyectos y en la resolución de prácticas diseñadas para grupos heterogéneos de estudiantes, respecto del dominio de sus competencias. En estecontexto, el mentor se desempeña como organizador y facilitador de los ajustes pedagógicos derivados de la individualización del proceso interactivo. Una interacción estrictamente docente que busca su desarrollo en la orientación personal del estudiante y su relación con el sistema de enseñanza y los objetivos de la institución a la que pertenece. De este modo “mentoring” surge desde la visión innovadora de una cátedra para plasmarse integralmente en un Proyecto de orden Institucional.Palabras ClaveInnovación, Virtualidad Áulica, Soporte, Interacció

Quantum dot-based multiphoton fluorescent pipettes for targeted neuronal electrophysiology

Targeting visually identified neurons for electrophysiological recording is a fundamental neuroscience technique; however, its potential is hampered by poor visualization of pipette tips in deep brain tissue. We describe quantum dot-coated glass pipettes that provide strong two-photon contrast at deeper penetration depths than those achievable with current methods. We demonstrated the pipettes' utility in targeted patch-clamp recording experiments and single-cell electroporation of identified rat and mouse neurons in vitro and in vivo

Operations aspects of the Fermilab Central Helium Liquefier Facility

The Fermilab Central Helium Liquefier (CHL) facility consists of helium and nitrogen reliquefier plants operated 24 hours-a-day to supply LHe at 4.6{degrees}K and LN{sub 2} for the Fermilab Tevatron superconducting proton-antiproton collider ring and to recover warm return gases. Operating aspects of CHL, including different equipment and systems reliability, availability, maintenance experience, safety concerns, and economics aspects are discussed

Neuronal Na+ Channels Are Integral Components of Pro-Arrhythmic Na+/Ca2+ Signaling Nanodomain That Promotes Cardiac Arrhythmias During β-Adrenergic Stimulation

SummaryAlthough triggered arrhythmias including catecholaminergic polymorphic ventricular tachycardia (CPVT) are often caused by increased levels of circulating catecholamines, the mechanistic link between β-adrenergic receptor (AR) stimulation and the subcellular/molecular arrhythmogenic trigger(s) is unclear. Here, we systematically investigated the subcellular and molecular consequences of β-AR stimulation in the promotion of catecholamine-induced cardiac arrhythmias. Using mouse models of cardiac calsequestrin-associated CPVT, we demonstrate that a subpopulation of Na+ channels, mainly the neuronal Na+ channels (nNav), colocalize with ryanodine receptor 2 (RyR2) and Na+/Ca2+ exchanger (NCX) and are a part of the β-AR-mediated arrhythmogenic process. Specifically, augmented Na+ entry via nNav in the settings of genetic defects within the RyR2 complex and enhanced sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA)-mediated SR Ca2+ refill is both an essential and a necessary factor for arrhythmogenesis. Furthermore, we show that augmentation of Na+ entry involves β-AR–mediated activation of CAMKII, subsequently leading to nNav augmentation. Importantly, selective pharmacological inhibition as well as silencing of Nav1.6 inhibit myocyte arrhythmic potential and prevent arrhythmias in vivo. Taken together, these data suggest that the arrhythmogenic alteration in Na+/Ca2+ handling evidenced ruing β-AR stimulation results, at least in part, from enhanced Na+ influx through nNav. Therefore, selective inhibition of these channels and of Nav1.6 in particular can serve as a potential antiarrhythmic therapy

Divided communities and contested landscapes: Mobility, development and shifting identities in migrant destination sites in Papua New Guinea

Internal conflicts at the local and national levels in several South Pacific countries have revealed the fragility of national unity and the difficulties nations face in governing and managing their own economic development. In Papua New Guinea, the focus of this paper, an uncertain economic future for many rural and urban communities, and rising inequalities in income opportunities and access to resources, have coincided with greater intolerance of migrants at sites of high in-migration by customary landowners and provincial and local authorities. This paper draws on fieldwork undertaken in the major oil palm growing regions of Papua New Guinea where migrants from densely populated regions of the country have settled on state land alienated from customary landowners. We examine how struggles over land, resource control and development are polarising migrant and landowner identities resulting in increasing tensions and episodic communal violence. A settler identity is emerging based on a narrative of nation building and national development, while an ethno-regional identity amongst customary landowners is undermining the citizen rights of migrants and challenging the role and authority of the state in land matters

Secondary education reform in Lesotho and Zimbabwe and the needs of rural girls: Pronouncements, policy and practice

Analysis of the educational needs of rural girls in Lesotho and Zimbabwe suggests a number of shortcomings in the current form of secondary education, and ways in which it might be modified so as to serve this sizeable group of students better. Several of the shortcomings, notably in relation to curricular irrelevance and excessive focus on examinations, have long been recognised, including by politicians. Yet political pronouncements are seldom translated into policy, and even where policy is formulated, reforms are seldom implemented in schools. This paper makes use of interviews with educational decision-makers in the two southern African countries and a range of documentary sources to explore why, despite the considerable differences between the two contexts, much needed educational reforms have been implemented in neither

Nitric Oxide Signaling Modulates Synaptic Transmission during Early Postnatal Development

Early γ-aminobutyric acid mediated (GABAergic) synaptic transmission and correlated neuronal activity are fundamental to network formation; however, their regulation during early postnatal development is poorly understood. Nitric oxide (NO) is an important retrograde messenger at glutamatergic synapses, and it was recently shown to play an important role also at GABAergic synapses in the adult brain. The subcellular localization and network effect of this signaling pathway during early development are so far unexplored, but its disruption at this early age is known to lead to profound morphological and functional alterations. Here, we provide functional evidence—using whole-cell recording—that NO signaling modulates not only glutamatergic but also GABAergic synaptic transmission in the mouse hippocampus during the early postnatal period. We identified the precise subcellular localization of key elements of the underlying molecular cascade using immunohistochemistry at the light—and electron microscopic levels. As predicted by these morpho-functional data, multineuron calcium imaging in acute slices revealed that this NO-signaling machinery is involved also in the control of synchronous network activity patterns. We suggest that the retrograde NO-signaling system is ideally suited to fulfill a general presynaptic regulatory role and may effectively fine-tune network activity during early postnatal development, while GABAergic transmission is still depolarizing

Dysfunction in the βII Spectrin-Dependent Cytoskeleton Underlies Human Arrhythmia.

Background: The cardiac cytoskeleton plays key roles in maintaining myocyte structural integrity in health and disease. In fact, human mutations in cardiac cytoskeletal elements are tightly linked with cardiac pathologies including myopathies, aortopathies, and dystrophies. Conversely, the link between cytoskeletal protein dysfunction in cardiac electrical activity is not well understood, and often overlooked in the cardiac arrhythmia field. Methods and Results: Here, we uncover a new mechanism for the regulation of cardiac membrane excitability. We report that βII spectrin, an actin-associated molecule, is essential for the post-translational targeting and localization of critical membrane proteins in heart. βII spectrin recruits ankyrin-B to the cardiac dyad, and a novel human mutation in the ankyrin-B gene disrupts the ankyrin-B/βII spectrin interaction leading to severe human arrhythmia phenotypes. Mice lacking cardiac βII spectrin display lethal arrhythmias, aberrant electrical and calcium handling phenotypes, and abnormal expression/localization of cardiac membrane proteins. Mechanistically, βII spectrin regulates the localization of cytoskeletal and plasma membrane/sarcoplasmic reticulum protein complexes that include the Na/Ca exchanger, RyR2, ankyrin-B, actin, and αII spectrin. Finally, we observe accelerated heart failure phenotypes in βII spectrin-deficient mice. Conclusions: Our findings identify βII spectrin as critical for normal myocyte electrical activity, link this molecule to human disease, and provide new insight into the mechanisms underlying cardiac myocyte biology

Bocepreviralapú hármas kezelés hatékonyságának és biztonságosságának retrospektív elemzése előrehaladott fibrosisstádiumú, hepatitis C-vírus 1-es genotípussal fertőzött, korábban sikertelenül kezelt magyar betegeknél

INTRODUCTION: During 2011 and 2013, 155 Hungarian hepatitis C genotype 1 infected patients, mostly with advanced liver fibrosis, who did not respond to prior peginterferon + ribavirin dual therapy, started boceprevir based triple therapy in an early access program. AIM AND METHOD: Efficacy and safety of the therapy was retrospectively assessed based on sustained virologic responses, as well as on frequency and type of serious adverse events and of those leading to therapy discontinuation. RESULTS: In an intent-to-treat analysis 39.4% patients (61/155) reached sustained virologic response. Amongst pervious relapsers, partial responders and null-responders 59.5%, 41.4 % and 22.9% (p<0.05 compared to the other two categories) reached sustained virologic response, respectively, while amongst non-cirrhotics and cirrhotics 52.5% and 31.3% (p<0.05 compared to the non-cirrhotics) achieved sutained virologic response, respectively. Six out of the 33 most difficult to cure patients (previous null responder and cirrhotic) have reached sustained virologic response (18.2%). Frequency of early discontinuations due to insufficient virologic response was 31.1%, while due to adverse event 10.3%. Reported frequency of serious adverse event was 9.8%. These events represented anemia, diarrhoea, depression, agranulocytosis, elevated aminotransferases, generalized dermatitis and severe gingivitis with loss of teeth, prolonged QT interval on ECG, generalized oedema and severe dyspnoea, uroinfection, exacerbation of Crohn's disease, Campylobacter pylori infection and unacceptable weakness and fatigue. Eight patients received transfusion, 4 patients erythropoietin and 1 granulocyte colony stimulating factor during therapy. No death has been reported. CONCLUSIONS: With boceprevir based triple therapy, one of the bests available in 2011-2013 in Hungary, a relevant proportion of hepatitis C infected patients with advanced liver fibrosis achieved sustained viral response. In this cohort, side-effects resembled those reported in registration studies, and resulted in therapy discontinuation with consequent treatment failure in a relevant number of patients. Efficacy and tolerability of boceprevir-based triple therapy are suboptimal, particularly in the most difficult to cure patient population. Orv. Hetil., 2016, 157(34), 1366-1374