פרסומים

In 2009, Xu et al. and Chaput et al. in Nature Medicine had argued that the main cause of death in sepsis is the release from neutrophil nets of nuclear histone, highly toxic to endothelial cells and that these polycations are major and unique virulence factors. Since 2009, numerous researchers have also suggested the involvement of histones in the pathophysiology of many clinical disorders. If histones are indeed major unique virulence toxic agents, then heparin, activated protein C and antibodies to histone should prove excellent antisepsis agents. However, this is provided that these agents are administered to patients early enough before the activation of the cytokine storms, immune responses and the coagulation cascades are irreversibly unleashed. This may not be practical, since a diagnosis of sepsis is usually made much later. Future identifications of novel early markers are therefore needed and a compilation of cocktails of antagonists may replace the faulty single antagonists tried for many years, but in vain, to prevent death in sepsis.

Viruses lack the basic machinery needed to replicate and therefore must hijack the host's metabolism to propagate. Virus-induced metabolic changes have yet to be systematically studied in the context of host transcriptional regulation, and such studies shoul offer insight into host-pathogen metabolic interplay. In this work we identified hepatitis C virus (HCV)-responsive regulators by coupling system-wide metabolic-flux analysis with targeted perturbation of nuclear receptors in primary human hepatocytes. We found HCV-induced upregulation of glycolysis, ketogenesis and drug metabolism, with glycolysis controlled by activation of HNF4α, ketogenesis by PPARα and FXR, and drug metabolism by PXR. Pharmaceutical inhibition of HNF4α reversed HCV-induced glycolysis, blocking viral replication while increasing apoptosis in infected cells showing virus-induced dependence on glycolysis. In contrast, pharmaceutical inhibition of PPARα or FXR reversed HCV-induced ketogenesis but increased viral replication, demonstrating a novel host antiviral response. Our results show that virus-induced changes to a host's metabolism can be detrimental to its life cycle, thus revealing a biologically complex relationship between virus and host. © Nature America, Inc.

Stabilized laser lines are highly desired for myriad of applications ranging from precise measurements to optical communications. While stabilization can be obtained by using molecular or atomic absorption references, these are limited to specific frequencies. On the other hand, resonators can be used as wide band frequency references. Unfortunately, such resonators are unstable and inaccurate. Here, we propose and experimentally demonstrate a chip-scale multispectral frequency standard replication operating in the spectral range of the near IR. This is obtained by frequency locking a microring resonator (MRR) to an acetylene absorption line. The MRR consists of a Si3N4 waveguides with microheater on top of it. The thermo-optic effect is utilized to lock one of the MRR resonances to an acetylene line. This locked MRR is then used to stabilize other laser sources at 980 nm and 1550 nm wavelength. By beating the stabilized laser to another stabilized laser, we obtained frequency instability floor of 4×10-9 at around 100 s in terms of Allan deviation. Such stable and accurate chip scale sources are expected to serve as important building block in diverse fields such as communication and metrology.

Cell-cell interactions play a key role in regeneration, differentiation, and basic tissue function taking place under physiological shear forces. However, current solutions to mimic such interactions by micro-patterning cells within microfluidic devices have low resolution, high fabrication complexity, and are limited to one or two cell types. Here, we present a microfluidic platform capable of laminar patterning of any biotinlabeled peptide using streptavidin-based surface chemistry. The design permits the generation of arbitrary cell patterns from heterogeneous mixtures in microfluidic devices. We demonstrate the robust co-patterning of α-CD24, α-ASGPR-1, and α- Tie2 antibodies for rapid isolation and co-patterning of mixtures of hepatocytes and endothelial cells. In addition to one-step isolation and patterning, our design permits step-wise patterning of multiple cell types and empty spaces to create complex cellular geometries in vitro. In conclusion, we developed a microfluidic device that permits the generation of perfusable tissue-like patterns in microfluidic devices by directly injecting complex cell mixtures such as differentiated stem cells or tissue digests with minimal sample preparation. © 2016 AIP Publishing LLC.

The food industry, especially small and medium enterprises (SMEs), is facing increasingly complex challenges, more regulation, as well as fierce local and global competition. Open innovation (OI) can enhance innovation options by accessing external assets and collaborations with unique opportunities, facilitating partnerships, and alleviating hurdles such as limited resources, R&D expertise, skills, etc. Highlighted topics include: adapting OI for the food industry's special needs, with a focus on SMEs' unique challenges, and the roles of academia and intellectual property. Examples provided depict SMEs with typical OI utilization and the steps required to initiate and develop new concepts. Specific recommendations include: collaboration, creation of a four-helix innovation ecosystem (industry, academia, government, and private sector), metrics to quantify academia's social responsibility, and revised curricula promoting OI to encourage SMEs involvement. OI presents a unique opportunity for all stakeholders, especially for SMEs, to proactively engage in meeting future challenges and opportunities. © 2016 Elsevier Inc. All rights reserved.

A single electron dynamic memory is designed based on the non-equilibrium dynamics of charge states in electrostatically defined metallic quantum dots. Using the orthodox theory for computing the transfer rates and a master equation, we model the dynamical response of devices consisting of a charge sensor coupled to either a single and or a double quantum dot subjected to a pulsed gate voltage. We show that transition rates between charge states in metallic quantum dots are characterized by an asymmetry that can be controlled by the gate voltage. This effect is more pronounced when the switching between charge states corresponds to a Markovian process involving electron transport through a chain of several quantum dots. By simulating the dynamics of electron transport we demonstrate that the quantum box operates as a finite-state machine that can be addressed by choosing suitable shapes and switching rates of the gate pulses. We further show that writing times in the ns range and retention memory times six orders of magnitude longer, in the ms range, can be achieved on the double quantum dot system using experimentally feasible parameters, thereby demonstrating that the device can operate as a dynamic single electron memory. Published by AIP Publishing.

The sensitivity of magnetic resonance imaging (MRI) depends strongly on nuclear spin polarisation and, motivated by this observation, dynamical nuclear spin polarisation has recently been applied to enhance MRI protocols (Kurhanewicz et al 2011 Neoplasia 13 81). Nuclear spins associated with the ¹³C carbon isotope (nuclear spin I = 1/2) in diamond possess uniquely long spin lattice relaxation times (Reynhardt and High 2011 Prog. Nucl. Magn. Reson. Spectrosc. 38 37). If they are present in diamond nanocrystals, especially when strongly polarised, they form a promising contrast agent for MRI. Current schemes for achieving nuclear polarisation, however, require cryogenic temperatures. Here we demonstrate an efficient scheme that realises optically induced ¹³C nuclear spin hyperpolarisation in diamond at room temperature and low ambient magnetic field. Optical pumping of a nitrogen-vacancy centre creates a continuously renewable electron spin polarisation which can be transferred to surrounding ¹³C nuclear spins. Importantly for future applications we also realise polarisation protocols that are robust against an unknown misalignment between magnetic field and crystal axis.

We study the reclamation process of a sodic soil by irrigation with water amended with calcium cations. In order to explore the entire range of time-dependent strategies, this task is framed as an optimal control problem, where the amendment rate is the control and the total rehabilitation time is the quantity to be minimized. We use a minimalist model of vertically averaged soil salinity and sodicity, in which the main feedback controlling the dynamics is the nonlinear coupling of soil water and exchange complex, given by the Gapon equation. We show that the optimal solution is a bang–bang control strategy, where the amendment rate is discontinuously switched along the process from a maximum value to zero. The solution enables a reduction in remediation time of about 50%, compared with the continuous use of good-quality irrigation water. Because of its general structure, the bang–bang solution is also shown to work for the reclamation of other soil conditions, such as saline–sodic soils. The novelty in our modeling approach is the capability of searching the entire “strategy space” for optimal time-dependent protocols. The optimal solutions found for the minimalist model can be then fine-tuned by experiments and numerical simulations, applicable to realistic conditions that include spatial variability and heterogeneities.

A vast theoretical literature shows that inefficient market structures may arise in free entry equilibria. Previous empirical work demonstrated that excessive entry may obtain in local radio markets. Our paper extends that literature by relaxing the assumption that stations are symmetric, allowing instead for endogenous station differentiation along both (observed) horizontal and (unobserved) vertical dimensions. We find that, in most broadcasting formats, a social planner who takes into account the welfare of market participants (stations and advertisers) would eliminate 50%-60% of the stations observed in equilibrium. In 80%-94.9% of markets that have high quality stations in the observed equilibrium, welfare could be unambiguously improved by converting one such station into low quality broadcasting. In contrast, it is never unambiguously welfare-enhancing to convert an observed low quality station into a high quality one. This suggests local over-provision of quality in the observed equilibrium, in addition to the finding of excessive entry.

Avian reovirus (ARV) is a disease-causing agent. The disease is prevented by vaccination with a genotype-specific vaccine while many variants of ARV exist in the field worldwide. Production of new attenuated vaccines is a long-term process and in the case of fast-mutating viruses, an impractical one. In the era of molecular biology, vaccines may be produced by using only the relevant protein for induction of neutralizing antibodies, enabling fast adjustment to the emergence of new genetic strains. Sigma C (SC) protein of ARV is a homotrimer that facilitates host-cell attachment and induce the production and secretion of neutralizing antibodies. The aim of this study was to identify the region of SC that will elicit a protective immune response. Full-length (residues 1-326) and two partial fragments of SC (residues 122-326 and 192-326) were produced in Escherichia coli. The SC fragment of residues 122-326 include the globular head, shaft and hinge domains, while eliminating intra-capsular region. This fragment induces significantly higher levels of anti-ARV antibodies than the shorter fragment or full length SC, which neutralized embryos infection by the virulent strain to a higher extent compared with the antibodies produced in response to the whole virus vaccine. Residues 122-326 fragment is assumed to be folded correctly, exposing linear as well as conformational epitopes that are identical to those of the native protein, while possibly excluding suppressor sequences. The results of this study may serve for the development of a recombinant subunit vaccine for ARV. © 2016 Elsevier Ltd.