Simultaneous measurement of the maximum oscillation amplitude and the transient decay time constant of the QCM reveals stiffness changes of the adlayer

Interpretation of adsorption kinetics measured with a quartz crystal microbalance (QCM) can be difficult for adlayers undergoing modification of their mechanical properties. We have studied the behavior of the oscillation amplitude, A 0, and the decay time constant, τ, of quartz during adsorption of proteins and cells, by use of a home-made QCM. We are able to measure simultaneously the frequency, f, the dissipation factor, D, the maximum amplitude, A 0, and the transient decay time constant, τ, every 300ms in liquid, gaseous, or vacuum environments. This analysis enables adsorption and modification of liquid/mass properties to be distinguished. Moreover the surface coverage and the stiffness of the adlayer can be estimated. These improvements promise to increase the appeal of QCM methodology for any applications measuring intimate contact of a dynamic material with a solid surfac

Linear response subordination to intermittent energy release in off-equilibrium aging dynamics

The interpretation of experimental and numerical data describing off-equilibrium aging dynamics crucially depends on the connection between spontaneous and induced fluctuations. The hypothesis that linear response fluctuations are statistically subordinated to irreversible outbursts of energy, so-called quakes, leads to predictions for averages and fluctuations spectra of physical observables in reasonable agreement with experimental results [see e.g. Sibani et al., Phys. Rev. B74:224407, 2006]. Using simulational data from a simple but representative Ising model with plaquette interactions, direct statistical evidence supporting the hypothesis is presented and discussed in this work. A strict temporal correlation between quakes and intermittent magnetization fluctuations is demonstrated. The external magnetic field is shown to bias the pre-existent intermittent tails of the magnetic fluctuation distribution, with little or no effect on the Gaussian part of the latter. Its impact on energy fluctuations is shown to be negligible. Linear response is thus controlled by the quakes and inherits their temporal statistics. These findings provide a theoretical basis for analyzing intermittent linear response data from aging system in the same way as thermal energy fluctuations, which are far more difficult to measure.Comment: 9 pages, 10 figures. Text improve

Talking to patients about biosimilars

Biologic therapies target aberrant pathways in diseases including diabetes, cancer and autoimmune disorders. Despite recent scientific advances, patient access to these agents can be limited. Biosimilars are designed to be highly similar to the originator biologic, targeting the same biological pathways, with comparable efficacy and safety. Biosimilars have the advantage of lower treatment costs, offering the potential for increased clinical use and patient access. Several biosimilars are approved for clinical use in the USA and Europe; however, there is a lack of awareness about biosimilars among healthcare providers and patients. This overview of the scientific basis of biosimilars and current indications aim to enhance discussions with patients and increase understanding of the role of biosimilars in individual treatment plans

Syntaxin 16 is a master recruitment factor for cytokinesis

Recently it was shown that both recycling endosome and endosomal sorting complex required for transport (ESCRT) components are required for cytokinesis, in which they are believed to act in a sequential manner to bring about secondary ingression and abscission, respectively. However, it is not clear how either of these complexes is targeted to the midbody and whether their delivery is coordinated. The trafficking of membrane vesicles between different intracellular organelles involves the formation of soluble N-ethylmalei­mide–sensitive factor attachment protein receptor (SNARE) complexes. Although membrane traffic is known to play an important role in cytokinesis, the contribution and identity of intracellular SNAREs to cytokinesis remain unclear. Here we demonstrate that syntaxin 16 is a key regulator of cytokinesis, as it is required for recruitment of both recycling endosome–associated Exocyst and ESCRT machinery during late telophase, and therefore that these two distinct facets of cytokinesis are inextricably linked

Somatic genome editing with CRISPR/Cas9 generates and corrects a metabolic disease

Germline manipulation using CRISPR/Cas9 genome editing has dramatically accelerated the generation of new mouse models. Nonetheless, many metabolic disease models still depend upon laborious germline targeting, and are further complicated by the need to avoid developmental phenotypes. We sought to address these experimental limitations by generating somatic mutations in the adult liver using CRISPR/Cas9, as a new strategy to model metabolic disorders. As proof-of-principle, we targeted the low-density lipoprotein receptor (Ldlr), which when deleted, leads to severe hypercholesterolemia and atherosclerosis. Here we show that hepatic disruption of Ldlr with AAV-CRISPR results in severe hypercholesterolemia and atherosclerosis. We further demonstrate that co-disruption of Apob, whose germline loss is embryonically lethal, completely prevented disease through compensatory inhibition of hepatic LDL production. This new concept of metabolic disease modeling by somatic genome editing could be applied to many other systemic as well as liver-restricted disorders which are difficult to study by germline manipulation

Cortical depth dependent functional responses in humans at 7T: improved specificity with 3D GRASE

Ultra high fields (7T and above) allow functional imaging with high contrast-to-noise ratios and improved spatial resolution. This, along with improved hardware and imaging techniques, allow investigating columnar and laminar functional responses. Using gradient-echo (GE) (T2* weighted) based sequences, layer specific responses have been recorded from human (and animal) primary visual areas. However, their increased sensitivity to large surface veins potentially clouds detecting and interpreting layer specific responses. Conversely, spin-echo (SE) (T2 weighted) sequences are less sensitive to large veins and have been used to map cortical columns in humans. T2 weighted 3D GRASE with inner volume selection provides high isotropic resolution over extended volumes, overcoming some of the many technical limitations of conventional 2D SE-EPI, whereby making layer specific investigations feasible. Further, the demonstration of columnar level specificity with 3D GRASE, despite contributions from both stimulated echoes and conventional T2 contrast, has made it an attractive alternative over 2D SE-EPI. Here, we assess the spatial specificity of cortical depth dependent 3D GRASE functional responses in human V1 and hMT by comparing it to GE responses. In doing so we demonstrate that 3D GRASE is less sensitive to contributions from large veins in superficial layers, while showing increased specificity (functional tuning) throughout the cortex compared to GE

Fluctuations in the coarsening dynamics of the O(N) model: are they similar to those in glassy systems?

We study spatio-temporal fluctuations in the non-equilibrium dynamics of the d dimensional O(N) in the large N limit. We analyse the invariance of the dynamic equations for the global correlation and response in the slow ageing regime under transformations of time. We find that these equations are invariant under scale transformations. We extend this study to the action in the dynamic generating functional finding similar results. This model therefore falls into a different category from glassy problems in which full time-reparametrisation invariance, a larger symmetry that emcompasses time scale invariance, is expected to be realised asymptotically. Consequently, the spatio-temporal fluctuations of the large N O(N) model should follow a different pattern from that of glassy systems. We compute the fluctuations of local, as well as spatially separated, two-field composite operators and responses, and we confront our results with the ones found numerically for the 3d Edwards-Anderson model and kinetically constrained lattice gases. We analyse the dependence of the fluctuations of the composite operators on the growing domain length and we compare to what has been found in super-cooled liquids and glasses. Finally, we show that the development of time-reparametrisation invariance in glassy systems is intimately related to a well-defined and finite effective temperature, specified from the modification of the fluctuation-dissipation theorem out of equilibrium. We then conjecture that the global asymptotic time-reparametrisation invariance is broken down to time scale invariance in all coarsening systems.Comment: 57 pages, 5 figure

Seronegative Herpes simplex Associated Esophagogastric Ulcer after Liver Transplantation

Herpes simplex infection is characterized by acute or subacute infection, often followed by a chronic carrier state. Consecutive recurrences may flare up if immunocompromise occurs. Herpes simplex associated esophagitis or duodenal ulcer have been reported in immunocompromised patients due to neoplasm, HIV/AIDS or therapeutically induced immune deficiency. Here we report the case of an HSV-DNA seronegative patient who developed grade III dysphagia 13 days after allogeneic liver transplantation. Endoscopy revealed an esophageal-gastric ulcer, and biopsy histopathology showed a distinct fibroplastic and capillary ulcer pattern highly suspicious for viral infection. Immunohistochemistry staining revealed a distinct nuclear positive anti-HSV reaction. Antiviral therapy with acyclovir and high-dose PPI led to a complete revision of clinical symptoms within 48 h. Repeat control endoscopy after 7 days showed complete healing of the former ulcer site at the gastroesophageal junction. Although the incidence of post-transplantation Herpes simplex induced gastroesophageal disease is low, the viral HSV ulcer may be included into a differential diagnosis if dysphagia occurs after transplantation even if HSV-DNA PCR is negative