A 1.82 m^2 ring laser gyroscope for nano-rotational motion sensing

We present a fully active-controlled He-Ne ring laser gyroscope, operating in square cavity 1.35 m in side. The apparatus is designed to provide a very low mechanical and thermal drift of the ring cavity geometry and is conceived to be operative in two different orientations of the laser plane, in order to detect rotations around the vertical or the horizontal direction. Since June 2010 the system is active inside the Virgo interferometer central area with the aim of performing high sensitivity measurements of environmental rotational noise. So far, continuous not attempted operation of the gyroscope has been longer than 30 days. The main characteristics of the laser, the active remote-controlled stabilization systems and the data acquisition techniques are presented. An off-line data processing, supported by a simple model of the sensor, is shown to improve the effective long term stability. A rotational sensitivity at the level of ten nanoradiants per squareroot of Hz below 1 Hz, very close to the required specification for the improvement of the Virgo suspension control system, is demonstrated for the configuration where the laser plane is horizontal

On the Potential of Large Ring Lasers

We describe a new ring laser with area A = 833 m^2 and update performance statistics for several such machines. Anandan & Chaio 1982 judged ring lasers inferior to matter interferometers as possible detectors of gravitational waves. However, we note that geophysically interesting results have been obtained from large ring lasers and that there is still a lot of room for improvements.Comment: accepted optics communication

Hypoxia-inducible factors not only regulate but also are myeloid-cell treatment targets

Hypoxia describes limited oxygen availability at the cellular level. Myeloid cells are exposed to hypoxia at various bodily sites and even contribute to hypoxia by consuming large amounts of oxygen during respiratory burst. Hypoxia-inducible factors (HIFs) are ubiquitously expressed heterodimeric transcription factors, composed of an oxygen-dependent α and a constitutive β subunit. The stability of HIF-1α and HIF-2α is regulated by oxygen-sensing prolyl-hydroxylases (PHD). HIF-1α and HIF-2α modify the innate immune response and are context dependent. We provide a historic perspective of HIF discovery, discuss the molecular components of the HIF pathway, and how HIF-dependent mechanisms modify myeloid cell functions. HIFs enable myeloid-cell adaptation to hypoxia by up-regulating anaerobic glycolysis. In addition to effects on metabolism, HIFs control chemotaxis, phagocytosis, degranulation, oxidative burst, and apoptosis. HIF-1α enables efficient infection defense by myeloid cells. HIF-2α delays inflammation resolution and decreases antitumor effects by promoting tumor-associated myeloid-cell hibernation. PHDs not only control HIF degradation, but also regulate the crosstalk between innate and adaptive immune cells thereby suppressing autoimmunity. HIF-modifying pharmacologic compounds are entering clinical practice. Current indications include renal anemia and certain cancers. Beneficial and adverse effects on myeloid cells should be considered and could possibly lead to drug repurposing for inflammatory disorders

General relativistic Sagnac formula revised

The Sagnac effect is a time or phase shift observed between two beams of light traveling in opposite directions in a rotating interferometer. We show that the standard description of this effect within the framework of general relativity misses the effect of deflection of light due to rotational inertial forces. We derive the necessary modification and demonstrate it through a detailed analysis of the square Sagnac interferometer rotating about its symmetry axis in Minkowski space-time. The role of the time shift in a Sagnac interferometer in the synchronization procedure of remote clocks as well as its analogy with the Aharanov-Bohm effect are revised.Comment: 11 pages, 3 figure

Hemophagocytic lymphohistiocytosis and thrombotic microangiopathy after parvovirus B19 infection and renal transplantation: a case report

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening disease characterized by hyperactivation of the immune system that causes hypercytokinemia and potentially multi organ failure. HLH can occur in patients with underlying rheumatic or autoinflammatory disorders. Additionally, HLH can develop in patients during infections or malignancies without a known genetic predisposition. CASE PRESENTATION: We herein report a patient, who presented with fever, both acute kidney and liver injury, anemia, thrombocytopenia and HSV stomatitis. HLH was diagnosed based on clinical criteria and qPCR revealed an acute parvovirus B19 infection as potential underlying infectious trigger. Treatment was started with both IVIG and dexamethasone. Subsequently, kidney biopsy demonstrated TMA. CONCLUSIONS: In rare cases both HLH and aHUS can occur simultaneously in a patient as a consequence of viral infections. Insights from this unusual case might help physicians understand this complex symptom constellation

Daratumumab for the treatment of refractory ANCA-associated vasculitis

OBJECTIVE: Treatment-refractory antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a life-threatening condition without evidence-based treatment options. One emerging treatment option for several antibody-mediated autoimmune diseases is the anti-CD38 antibody daratumumab, which depletes autoantibody-secreting plasma cells. METHODS: We treated two patients with severe life-threatening AAV with renal and pulmonary manifestation despite induction therapy with rituximab and cyclophosphamide with four to eight doses of 1800 mg daratumumab. We followed clinical and immunological responses. RESULTS: The first patient with myeloperoxidase-ANCA-positive microscopic polyangiitis had resolution of pneumonitis and pleuritis and stabilisation of kidney function after daratumumab. The second patient with proteinase 3-ANCA-positive granulomatosis with polyangiitis, diffuse alveolar haemorrhage necessitating extracorporeal membrane oxygenation (ECMO) and acute kidney failure, requiring kidney replacement therapy, was weaned off ECMO, mechanical ventilation and dialysis and discharged home after daratumumab. Clinical improvement was paralleled by a strong reduction in serum ANCA levels as well as total IgG, indicating depletion of plasma cells. Apart from the depletion of CD38(+) natural killer cells, blood leucocyte levels were not notably influenced by daratumumab. Only mild adverse events, such as hypogammaglobulinaemia and an upper respiratory tract infection occurred. CONCLUSION: Daratumumab was safe and effective in inducing remission in two patients with severe treatment-refractory AAV, warranting prospective clinical trials to establish safety and efficacy

Recurrent early filter clotting during continuous veno-venous hemodialysis with regional citrate anticoagulation is linked to systemic thrombin generation and heparin induced thrombocytopenia type II: a retrospective analysis

OBJECTIVE: Regional citrate anticoagulation (RCA) for continuous renal replacement therapy (CRRT) is widely used and leads to an excellent clottingfree filter survival. Despite strict adherence to protocols, in some cases recurrent early filter-clotting occurs. The aim of this observational study was to evaluate the underlying causes and the efficacy of interventions in patients with early recurrent filter-clotting during RCA. METHODS: In a retrospective analysis of a cohort of 1183 patients treated with RCA-CRRT we detected 12 patients with early filter-clotting unrelated to protocol violation or any obvious technical or medical reason. RESULTS: All patients were systemically anticoagulated with low molecular weight or unfractionated heparin for at least 24h before initiation of Continuous Veno-Venous Hemodialysis with RCA (RCA-CVVHD). During RCA, all postfilter ionized calcium concentrations were in the target range (mean 0.33±0.05 mmol/L). At the time of the first clotting event, thrombocyte counts were 168±66/ nL. After the clotting events, the systemic anticoagulation was switched to argatroban in all patients. With systemic anticoagulation using argatroban filter lifetime of RCA-CVVHD increased significantly (p<0.001) and clotting-events decreased from 0.61 to 0.10 per 24h. All patients were tested for HIT and 5/12 (42%) had a positive test for hep-PF4-antibodies. Application of argatroban significantly reduced early filter-clotting both in HIT-positive patients as well as in HIT-negative patients. At the time of the first clotting event, no patient had clinical signs of thrombosis or thromboembolism. However, during follow up a thromboembolic event occurred in three patients. CONCLUSION: In patients with recurrent early filter-clotting despite strict adherence to the citrate protocol undetected HIT or other causes of thrombin activation may be present. Therefore, patients with recurrent early filter clotting in RCA-CVVHD should be screened for HIT or other conditions that may activate thrombin. A significant improvement of filter run-time can be achieved by systemic administration of a thrombin inhibitor both in patients with and without HIT

The theory of canonical perturbations applied to attitude dynamics and to the Earth rotation. Osculating and nonosculating Andoyer variables

The Hamiltonian theory of Earth rotation, known as the Kinoshita-Souchay theory, operates with nonosculating Andoyer elements. This situation parallels a similar phenomenon that often happens (but seldom gets noticed) in orbital dynamics, when the standard Lagrange-type or Delaunay-type planetary equations unexpectedly render nonosculating orbital elements. In orbital mechanics, osculation loss happens when a velocity-dependent perturbation is plugged into the standard planetary equations. In attitude mechanics, osculation is lost when an angular-velocity-dependent disturbance is plugged in the standard dynamical equations for the Andoyer elements. We encounter exactly this situation in the theory of Earth rotation, because this theory contains an angular-velocity-dependent perturbation (the switch from an inertial frame to that associated with the precessing ecliptic of date). While the osculation loss does not influence the predictions for the figure axis of the planet, it considerably alters the predictions for the instantaneous spin-axis' orientation. We explore this issue in great detail

Coherent matter wave inertial sensors for precision measurements in space

We analyze the advantages of using ultra-cold coherent sources of atoms for matter-wave interferometry in space. We present a proof-of-principle experiment that is based on an analysis of the results previously published in [Richard et al., Phys. Rev. Lett., 91, 010405 (2003)] from which we extract the ratio h/m for 87Rb. This measurement shows that a limitation in accuracy arises due to atomic interactions within the Bose-Einstein condensate