A micro-perfusion chamber for single-cell fluorescence measurements

Abstract A versatile closed micro-perfusion chamber designed for single-cell fluorescence measurements under maximum microscopic magnification is described. Glass coverslips with adherent cells can be attached to the top or bottom of the chamber, depending on whether an inverted or an upright microscope is used. Eight conical holes drilled in the side of the chamber serve for the insertion of plugs with attachments for perfusion, rapid injection of small amounts of reagents, temperature measurements or for heating the interior of the chamber. Materials used in the construction of the chamber are non-toxic and resistant to standard sterilization procedures. Perfusion and temperature properties of the chamber are described. Single cell fluorescence measurements are presented in human monocyte-derived macrophages in which NAD(P)H and intracellular calcium are measured

Type-II Bose-Mott insulators

The Mott insulating state formed from bosons is ubiquitous in solid He-4, cold atom systems, Josephson junction networks and perhaps underdoped high-Tc superconductors. We predict that close to the quantum phase transition to the superconducting state the Mott insulator is not at all as featureless as is commonly believed. In three dimensions there is a phase transition to a low temperature state where, under influence of an external current, a superconducting state consisting of a regular array of 'wires' that each carry a quantized flux of supercurrent is realized. This prediction of the "type-II Mott insulator" follows from a field theoretical weak-strong duality, showing that this 'current lattice' is the dual of the famous Abrikosov lattice of magnetic fluxes in normal superconductors. We argue that this can be exploited to investigate experimentally whether preformed Cooper pairs exist in high-Tc superconductors.Comment: RevTeX, 17 pages, 6 figures, published versio

Theoretical Black Hole Mass Distributions

We derive the theoretical distribution function of black hole masses by studying the formation processes of black holes. We use the results of recent 2D simulations of core-collapse to obtain the relation between remnant and progenitor masses and fold it with an initial mass function for the progenitors. We examine how the calculated black-hole mass distributions are modified by (i) strong wind mass loss at different evolutionary stages of the progenitors, and (ii) the presence of close binary companions to the black-hole progenitors. Thus, we are able to derive the binary black hole mass distribution. The compact remnant distribution is dominated by neutron stars in the mass range 1.2-1.6Msun and falls off exponentially at higher remnant masses. Our results are most sensitive to mass loss from winds which is even more important in close binaries. Wind mass-loss causes the black hole distribution to become flatter and limits the maximum possible black-hole mass (<10-15Msun). We also study the effects of the uncertainties in the explosion and unbinding energies for different progenitors. The distributions are continuous and extend over a broad range. We find no evidence for a gap at low values (3-5Msun) or for a peak at higher values (~7Msun) of black hole masses, but we argue that our black hole mass distribution for binaries is consistent with the current sample of measured black-hole masses in X-ray transients. We discuss possible biases against the detection or formation of X-ray transients with low-mass black holes. We also comment on the possibility of black-hole kicks and their effect on binaries.Comment: 22 pages, submitted to Ap

A rare cause of acute ST-elevation myocardial infarction:case report of native aortic valve thrombosis

Background One to 13% of all patients with the clinical diagnosis of an acute coronary syndrome (ACS) show no evidence of significant obstructive coronary artery disease on angiography. Less common causes should be considered in those situations. A very rare cause of ACS is native aortic valve thrombosis. Case summary A 69-year-old previously healthy woman presented with acute chest pain. The electrocardiogram showed an anterolateral ST-elevation myocardial infarction (STEMI). She was immediately transferred for primary percutaneous coronary intervention. Shortly after arriving in hospital her condition deteriorated, with development of cardiogenic shock necessitating cardiopulmonary resuscitation. A coronary angiogram was performed during resuscitation that did not reveal any obstructive coronary artery disease. Echocardiography showed no pericardial effusion, no significant left-sided valve pathology, no signs of an aortic dissection or pulmonary embolism. She died of cardiogenic shock of unknown cause. Permission for autopsy was obtained. Pathologic examination revealed a large anterolateral myocardial infarction caused by a mass attached to the bottom of the left coronary cusp of the native aortic valve, which was large enough to occlude the ostium of the left main coronary artery. Microscopic analysis showed a thrombus of unknown origin. The aortic valve itself showed no signs of pathology. Discussion An ST-elevation myocardial infarction due to native aortic valve thrombosis is a rare condition, especially when there are no significant valvular abnormalities. This case demonstrates that thrombosis can develop in an apparently healthy middle-aged woman without any history of thrombotic disease

Dynamic regulation of airway surface liquid pH by TMEM16A and SLC26A4 in cystic fibrosis nasal epithelia with rare mutations

Copyright \ua9 2023 the Author(s). Published by PNAS. In cystic fibrosis (CF), defects in the CF transmembrane conductance regulator (CFTR) channel lead to an acidic airway surface liquid (ASL), which compromises innate defence mechanisms, predisposing to pulmonary failure. Restoring ASL pH is a potential therapy for people with CF, particularly for those who cannot benefit from current highly effective modulator therapy. However, we lack a comprehensive understanding of the complex mechanisms underlying ASL pH regulation. The calcium-activated chloride channel, TMEM16A, and the anion exchanger, SLC26A4, have been proposed as targets for restoring ASL pH, but current results are contradictory and often utilise nonphysiological conditions. To provide better evidence for a role of these two proteins in ASL pH homeostasis, we developed an efficient CRISPR-Cas9-based approach to knock-out (KO) relevant transporters in primary airway basal cells lacking CFTR and then measured dynamic changes in ASL pH under thin-film conditions in fully differentiated airway cultures, which better simulate the in vivo situation. Unexpectantly, we found that both proteins regulated steady-state as well as agonist-stimulated ASL pH, but only under inflammatory conditions. Furthermore, we identified two Food and Drug Administration (FDA)-approved drugs which raised ASL pH by activating SLC26A4. While we identified a role for SLC26A4 in fluid absorption, KO had no effect on cyclic adenosine monophosphate (cAMP)-stimulated fluid secretion in airway organoids. Overall, we have identified a role of TMEM16A in ASL pH homeostasis and shown that both TMEM16A and SLC26A4 could be important alternative targets for ASL pH therapy in CF, particularly for those people who do not produce any functional CFTR

Management of Neuropsychiatric Systemic Lupus Erythematosus: Current Approaches and Future Perspectives

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a generic definition referring to a series of neurological and psychiatric symptoms directly related to systemic lupus erythematosus (SLE). NPSLE includes heterogeneous and rare neuropsychiatric (NP) manifestations involving both the central and peripheral nervous system. Due to the lack of a gold standard, the attribution of NP symptoms to SLE represents a clinical challenge that obligates the strict exclusion of any other potential cause. In the acute setting, management of these patients does not differ from other non-SLE subjects presenting with the same NP manifestation. Afterwards, an individualized therapeutic strategy, depending on the presenting manifestation and severity of symptoms, must be started. Clinical trials in NPSLE are scarce and most of the data are extracted from case series and case reports. High-dose glucocorticoids and intravenous cyclophosphamide remain the cornerstone for patients with severe symptoms that are thought to reflect inflammation or an underlying autoimmune process. Rituximab, intravenous immunoglobulins, or plasmapheresis may be used if response is not achieved. When patients present with mild to moderate NP manifestations, or when maintenance therapy is warranted, azathioprine and mycophenolate may be considered. When symptoms are thought to reflect a thrombotic underlying process, anticoagulation and antiplatelet agents are the mainstay of therapy, especially if antiphospholipid antibodies or antiphospholipid syndrome are present. Recent trials on SLE using new biologicals, based on newly understood SLE mechanisms, have shown promising results. Based on what we currently know about its pathogenesis, it is tempting to speculate how these new therapies may affect the management of NPSLE patients. This article provides a comprehensive and critical review of the literature on

An Optical Study of BG Geminorum: An Ellipsoidal Binary with an Unseen Primar Star

We describe optical photometric and spectroscopic observations of the bright variable BG Geminorum. Optical photometry shows a pronounced ellipsoidal variation of the K0 I secondary, with amplitudes of ~0.5 mag at VRI and a period of 91.645 days. A deep primary eclipse is visible for wavelengths < 4400A; a shallower secondary eclipse is present at longer wavelengths. Eclipse timings and the radial velocity curve of the K0 secondary star indicate an interacting binary where a lobe-filling secondary, M_2 ~ 0.5 Msun, transfers material into a extended disk around a massive primary, M_1 ~ 4.5 Msun. The primary star is either an early B-type star or a black hole. If it did contain a black hole, BG Gem would be the longest period black hole binary known by a factor of 10, as well as the only eclipsing black hole binary system.Comment: 27 pages, includes 8 figures and 5 tables, accepted to A

Electrodynamics of Abrikosov vortices: the Field Theoretical Formulation

Electrodynamic phenomena related to vortices in superconductors have been studied since their prediction by Abrikosov, and seem to hold no fundamental mysteries. However, most of the effects are treated separately, with no guiding principle. We demonstrate that the relativistic vortex worldsheet in spacetime is the object that naturally conveys all electric and magnetic information, for which we obtain simple and concise equations. Breaking Lorentz invariance leads to down-to-earth Abrikosov vortices, and special limits of these equations include for instance dynamic Meissner screening and the AC Josephson relation. On a deeper level, we explore the electrodynamics of two-form sources in the absence of electric monopoles, in which the electromagnetic field strength itself acquires the characteristics of a gauge field. This novel framework leaves room for unexpected surprises.Comment: LaTeX, 23 pages, 5 figure

Het doden van eendagshaantjes, kan dat niet anders? : opvattingen van 'het publiek' over alternatieven voor het doden van eendagskuikens

Met focusgroepen en een (internet)enquête zijn de opvattingen van 'het publiek' over mogelijke alternatieven voor het doden van eendagshaantjes onderzocht. Er bleek geen eenduidige voorkeur voor een specifiek alternatief; nader onderzoek naar de haalbaarheid van enkele alternatieven is wenselij