Rare Transition Events in Nonequilibrium Systems with State-Dependent Noise: Application to Stochastic Current Switching in Semiconductor Superlattices

Using recent mathematical advances, a geometric approach to rare noise-driven transition events in nonequilibrium systems is given, and an algorithm for computing the maximum likelihood transition curve is generalized to the case of state-dependent noise. It is applied to a model of electronic transport in semiconductor superlattices to investigate transitions between metastable electric field distributions. When the applied voltage $V$ is varied near a saddle-node bifurcation at $V_th$, the mean life time $$ of the initial metastable state is shown to scale like $log \propto |V_th - V|^{3/2}$ as $V\to V_th$

Relaxation processes of point defects in vitreous silica from femtosecond to nanoseconds

We studied ultrafast relaxation of localized excited states at Ge-related oxygen deficient centers in silica using femtosecond transient-absorption spectroscopy. The relaxation dynamics exhibits a biexponential decay, which we ascribe to the departure from the Frank-Condon region of the first excited singlet state in 240 fs, followed by cooling in ∼10 ps. At later times, a nonexponential relaxation spanning up to 40 ns occurs, which is fitted with an inhomogeneous distribution of nonradiative relaxation rates, following a chi-square distribution with one degree of freedom. This reveals several analogies with phenomena such as neutron reactions, quantum dot blinking, or intramolecular vibrational redistribution. © 2008 American Institute of Physics.Peer Reviewe

Оценка состояния протяженных выработок с длительным сроком службы шахт Центрального Донбасса на примере Шахтоуправления «Покровское»

Chemokines critically control the infiltration of immune cells upon liver injury, thereby promoting hepatic inflammation and fibrosis. The chemokine receptor CCR8 can affect trafficking of monocytes/macrophages, monocyte-derived dendritic cells (DCs) and T-helper cell (Th) subsets, but its role in liver diseases is currently unknown. To investigate the functional role of CCR8 in liver diseases, ccr8(−/−) and wild-type (WT) mice were subjected to chronic experimental injury models of carbon tetrachloride (CCl(4)) administration and surgical bile duct ligation (BDL). CCR8 was strongly up-regulated in the injured liver. Ccr8(−/−) mice displayed attenuated liver damage (e.g., ALT, histology, and TUNEL) compared to WT mice and were also protected from liver fibrosis in two independent injury models. Flow cytometry revealed reduced infiltrates of liver macrophages, neutrophils and natural killer cells, whereas hepatic CD4(+) T cells increased. The main CCR8-expressing cells in the liver were hepatic macrophages, and CCR8 was functionally necessary for CCL1-directed migration of inflammatory but not for nonclassical monocytes into the liver. Moreover, the phenotype of liver macrophages from injured ccr8(−/−) animals was altered with increased expression of DC markers and enhanced expression of T-cell-attracting chemokine macrophage inflammatory protein 1-alpha (MIP-1α/CCL3). Correspondingly, hepatic CD4(+) T cells showed increased Th1 polarization and reduced Th2 cells in CCR8-deficient animals. Liver fibrosis progression, but also subsequent T-cell alterations, could be restored by adoptively transferring CCR8-expressing monocytes/macrophages into ccr8(−/−) mice during experimental injury. CONCLUSIONS: CCR8 critically mediates hepatic macrophage recruitment upon injury, which subsequently shapes the inflammatory response in the injured liver, affecting macrophage/DC and Th differentiation. CCR8 deficiency protects the liver against injury, ameliorating initial inflammatory responses and hepatic fibrogenesis. Inhibition of CCR8 or its ligand, CCL1, might represent a successful therapeutic target to limit liver inflammation and fibrosis progression

Clinical Manifestations and Case Management of Ebola Haemorrhagic Fever caused by a newly identified virus strain, Bundibugyo, Uganda, 2007-2008

A confirmed Ebola haemorrhagic fever (EHF) outbreak in Bundibugyo, Uganda, November 2007-February 2008, was caused by a putative new species (Bundibugyo ebolavirus). It included 93 putative cases, 56 laboratory-confirmed cases, and 37 deaths (CFR = 25%). Study objectives are to describe clinical manifestations and case management for 26 hospitalised laboratory-confirmed EHF patients. Clinical findings are congruous with previously reported EHF infections. The most frequently experienced symptoms were non-bloody diarrhoea (81%), severe headache (81%), and asthenia (77%). Seven patients reported or were observed with haemorrhagic symptoms, six of whom died. Ebola care remains difficult due to the resource-poor setting of outbreaks and the infection-control procedures required. However, quality data collection is essential to evaluate case definitions and therapeutic interventions, and needs improvement in future epidemics. Organizations usually involved in EHF case management have a particular responsibility in this respect

The Geometry of Most Probable Trajectories in Noise-Driven Dynamical Systems

This paper presents a heuristic derivation of a geometric minimum action method that can be used to determine most-probable transition paths in noise-driven dynamical systems. Particular attention is focused on systems that violate detailed balance, and the role of the stochastic vorticity tensor is emphasized. The general method is explored through a detailed study of a two-dimensional quadratic shear flow which exhibits bifurcating most-probable transition pathways.Comment: 8 pages, 7 figure

A low-cost fluorescence reader for in vitro transcription and nucleic acid detection with Cas13a

Point-of-care testing (POCT) in low-resource settings requires tools that can operate independently of typical laboratory infrastructure. Due to its favorable signal-to-background ratio, a wide variety of biomedical tests utilize fluorescence as a readout. However, fluorescence techniques often require expensive or complex instrumentation and can be difficult to adapt for POCT. To address this issue, we developed a pocket-sized fluorescence detector costing less than $15 that is easy to manufacture and can operate in low-resource settings. It is built from standard electronic components, including an LED and a light dependent resistor, filter foils and 3D printed parts, and reliably reaches a lower limit of detection (LOD) of. 6.8 nM fluorescein, which is sufficient to follow typical biochemical reactions used in POCT applications. All assays are conducted on filter paper, which allows for a flat detector architecture to improve signal collection. We validate the device by quantifying in vitro RNA transcription and also demonstrate sequence-specific detection of target RNAs with an LOD of 3.7 nM using a Cas13a-based fluorescence assay. Cas13a is an RNA-guided, RNA-targeting CRISPR effector with promiscuous RNase activity upon recognition of its RNA target. Cas13a sensing is highly specific and adaptable and in combination with our detector represents a promising approach for nucleic acid POCT. Furthermore, our open-source device may be used in educational settings, through providing low cost instrumentation for quantitative assays or as a platform to integrate hardware, software and biochemistry concepts in the future

Venetoclax enhances the efficacy of therapeutic antibodies in B-cell malignancies by augmenting tumor cell phagocytosis

Immunotherapy has evolved as a powerful tool for the treatment of B-cell malignancies, and patient outcomes have improved by combining therapeutic antibodies with conventional chemotherapy. Overexpression of antiapoptotic B-cell lymphoma 2 (Bcl-2) is associated with a poor prognosis, and increased levels have been described in patients with "double-hit" diffuse large B-cell lymphoma, a subgroup of Burkitt's lymphoma, and patients with pediatric acute lymphoblastic leukemia harboring a t(17;19) translocation. Here, we show that the addition of venetoclax (VEN), a specific Bcl-2 inhibitor, potently enhanced the efficacy of the therapeutic anti-CD20 antibody rituximab, anti-CD38 daratumumab, and anti-CD19-DE, a proprietary version of tafasitamab. This was because of an increase in antibody-dependent cellular phagocytosis by macrophages as shown in vitro and in vivo in cell lines and patient-derived xenograft models. Mechanistically, double-hit lymphoma cells subjected to VEN triggered phagocytosis in an apoptosis-independent manner. Our study identifies the combination of VEN and therapeutic antibodies as a promising novel strategy for the treatment of B-cell malignancies

High central venous saturation after cardiac surgery is associated with increased organ failure and long-term mortality: an observational cross-sectional study

Abstract Introduction Central venous saturation (ScvO2) monitoring has been suggested to address the issue of adequate cardiocirculatory function in the context of cardiac surgery. The aim of this study was to determine the impact of low (L) (&lt;60%), normal (N) (60%-80%), and high (H) (&gt;80%) ScvO2 measured on intensive care unit (ICU) admission after cardiac surgery. Methods We conducted a retrospective, cross-sectional, observational study at three ICUs of a university hospital department for anaesthesiology and intensive care. Electronic patient records of all adults who underwent cardiac surgery between 2006 and 2013 and available admission measurements of ScvO2 were examined. Patients were allocated to one of three groups according to first ScvO2 measurement after ICU admission: group L (&lt;60%), group N (60%-80%), and group H (&gt;80%). Primary end-points were in-hospital and 3-year follow-up survival. Results Data from 4,447 patients were included in analysis. Low and high initial measurements of ScvO2 were associated with increased in-hospital mortality (L: 5.6%; N: 3.3%; H: 6.8%), 3-year follow-up mortality (L: 21.6%; N: 19.3%; H: 25.8%), incidence of post-operative haemodialysis (L: 11.5%; N: 7.8%; H: 15.3%), and prolonged hospital length of stay (L: 13 days, 9–22; N: 12 days, 9–19; H: 14 days, 9–21). After adjustment for possible confounding variables, an initial ScvO2 above 80% was associated with adjusted hazard ratios of 2.79 (95% confidence interval (CI) 1.565-4.964, P &lt;0.001) for in-hospital survival and 1.31 (95% CI 1.033-1.672, P = 0.026) for 3-year follow-up survival. Conclusions Patients with high ScvO2 were particularly affected by unfavourable outcomes. Advanced haemodynamic monitoring may help to identify patients with high ScvO2 who developed extraction dysfunction and to establish treatment algorithms to improve patient outcome in these patients. </jats:sec