Quantum probe and design for a chemical compass with magnetic nanostructures

Magnetic fields as weak as Earth's may affect the outcome of certain photochemical reactions that go through a radical pair intermediate. When the reaction environment is anisotropic, this phenomenon can form the basis of a chemical compass and has been proposed as a mechanism for animal magnetoreception. Here, we demonstrate how to optimize the design of a chemical compass with a much better directional sensitivity simply by a gradient field, e.g. from a magnetic nanostructure. We propose an experimental test of these predictions, and suggest design principles for a hybrid metallic-organic chemical compass. In addition to the practical interest in designing a biomimetic weak magnetic field sensor, our result shows that gradient fields can server as powerful tools to probe spin correlations in radical pair reactions.Comment: 8 pages, 6 figures, comments are welcom

Induction chemotherapy in locally advanced squamous cell carcinoma of the head and neck: role, controversy, and future directions.

BackgroundThe value of induction chemotherapy (ICT) remains under investigation despite decades of research. New advancements in the field, specifically regarding the induction regimen of choice, have reignited interest in this approach for patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). Sufficient evidence has accumulated regarding the benefits and superiority of TPF (docetaxel, cisplatin, and fluorouracil) over the chemotherapy doublet cisplatin and fluorouracil. We therefore sought to collate and interpret the available data and further discuss the considerations for delivering ICT safely and optimally selecting suitable post-ICT regimens.DesignWe nonsystematically reviewed published phase III clinical trials on TPF ICT in a variety of LA SCCHN patient populations conducted between 1990 and 2017.ResultsTPF may confer survival and organ preservation benefits in a subgroup of patients with functionally inoperable or poor-prognosis LA SCCHN. Additionally, patients with operable disease or good prognosis (who are not candidates for organ preservation) may benefit from TPF induction in terms of reducing local and distant failure rates and facilitating treatment deintensification in selected populations. The safe administration of TPF requires treatment by a multidisciplinary team at an experienced institution. The management of adverse events associated with TPF and post-ICT radiotherapy-based treatment is crucial. Finally, post-ICT chemotherapy alternatives to cisplatin concurrent with radiotherapy (i.e. cetuximab or carboplatin plus radiotherapy) appear promising and must be investigated further.ConclusionsTPF is an evidence-based ICT regimen of choice in LA SCCHN and confers benefits in suitable patients when it is administered safely by an experienced multidisciplinary team and paired with the optimal post-ICT regimen, for which, however, no consensus currently exists

Evidence-Based Treatment Options in Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck.

The major development of the past decade in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) was the introduction of cetuximab in combination with platinum plus 5-fluorouracil chemotherapy (CT), followed by maintenance cetuximab (the EXTREME regimen). This regimen is supported by a phase 3 randomized trial and subsequent observational studies, and it confers well-documented survival benefits, with median survival ranging between approximately 10 and 14 months, overall response rates between 36 and 44%, and disease control rates of over 80%. Furthermore, as indicated by patient-reported outcome measures, the addition of cetuximab to platinum-based CT leads to a significant reduction in pain and problems with social eating and speech. Conversely, until very recently, there has been a lack of evidence-based second-line treatment options, and the therapies that have been available have shown low response rates and poor survival outcomes. Presently, a promising new treatment option in R/M SCCHN has emerged: immune checkpoint inhibitors (ICIs), which have demonstrated favorable results in second-line clinical trials. Nivolumab and pembrolizumab are the first two ICIs that were approved by the US Food and Drug Administration. We note that the trials that showed benefit with ICIs included not only patients who previously received ≥1 platinum-based regimens for R/M SCCHN but also patients who experienced recurrence within 6 months after combined modality therapy with a platinum agent for locally advanced disease. In this review, we outline the available clinical and observational evidence for the EXTREME regimen and the initial results from clinical trials for ICIs in patients with R/M SCCHN. We propose that these treatment options can be integrated into a new continuum of care paradigm, with first-line EXTREME regimen followed by second-line ICIs. A number of ongoing clinical trials are comparing regimens with ICIs, alone and in combination with other ICIs or CT, with the EXTREME regimen for first-line treatment of R/M SCCHN. As we eagerly await the results of these trials, the EXTREME regimen remains the standard of care for the first-line treatment of R/M SCCHN

Topology and energy transport in networks of interacting photosynthetic complexes

We address the role of topology in the energy transport process that occurs in networks of photosynthetic complexes. We take inspiration from light harvesting networks present in purple bacteria and simulate an incoherent dissipative energy transport process on more general and abstract networks, considering both regular structures (Cayley trees and hyperbranched fractals) and randomly-generated ones. We focus on the the two primary light harvesting complexes of purple bacteria, i.e., the LH1 and LH2, and we use network-theoretical centrality measures in order to select different LH1 arrangements. We show that different choices cause significant differences in the transport efficiencies, and that for regular networks centrality measures allow to identify arrangements that ensure transport efficiencies which are better than those obtained with a random disposition of the complexes. The optimal arrangements strongly depend on the dissipative nature of the dynamics and on the topological properties of the networks considered, and depending on the latter they are achieved by using global vs. local centrality measures. For randomly-generated networks a random arrangement of the complexes already provides efficient transport, and this suggests the process is strong with respect to limited amount of control in the structure design and to the disorder inherent in the construction of randomly-assembled structures. Finally, we compare the networks considered with the real biological networks and find that the latter have in general better performances, due to their higher connectivity, but the former with optimal arrangements can mimic the real networks' behaviour for a specific range of transport parameters. These results show that the use of network-theoretical concepts can be crucial for the characterization and design of efficient artificial energy transport networks.Comment: 14 pages, 16 figures, revised versio

Structure and dynamics of the E. coli chemotaxis core signaling complex by cryo-electron tomography and molecular simulations

To enable the processing of chemical gradients, chemotactic bacteria possess large arrays of transmembrane chemoreceptors, the histidine kinase CheA, and the adaptor protein CheW, organized as coupled core-signaling units (CSU). Despite decades of study, important questions surrounding the molecular mechanisms of sensory signal transduction remain unresolved, owing especially to the lack of a high-resolution CSU structure. Here, we use cryo-electron tomography and sub-tomogram averaging to determine a structure of the Escherichia coli CSU at sub-nanometer resolution. Based on our experimental data, we use molecular simulations to construct an atomistic model of the CSU, enabling a detailed characterization of CheA conformational dynamics in its native structural context. We identify multiple, distinct conformations of the critical P4 domain as well as asymmetries in the localization of the P3 bundle, offering several novel insights into the CheA signaling mechanism

Imprint of Reionization on the Cosmic Microwave Background Bispectrum

We study contributions to the cosmic microwave background (CMB) bispectrum from non-Gaussianity induced by secondary anisotropies during reionization. Large-scale structure in the reionized epoch both gravitational lenses CMB photons and produces Doppler shifts in their temperature from scattering off electrons in infall. The resulting correlation is potentially observable through the CMB bispectrum. The second-order Ostriker-Vishniac also couples to a variety of linear secondary effects to produce a bispectrum. For the currently favored flat cosmological model with a low matter content and small optical depth in the reionized epoch \tau \la 0.3, however, these bispectrum contributions are well below the detection threshold of MAP and at or below that of Planck, given their cosmic and noise variance limitations. At the upper end of this range, they can serve as an extra source of noise for measurements with Planck of either primordial nongaussianity or that induced by the correlation of gravitational lensing with the integrated Sachs-Wolfe and the thermal Sunyaev-Zel'dovich effects. We include a discussion of the general properties of the CMB bispectrum, its configuration dependence for the various effects, and its computation in the Limber approximation and beyond.Comment: 17 pages, 10 figures (with emulateapj.sty); submitted to Ap

Quantum control and entanglement in a chemical compass

The radical pair mechanism is one of the two main hypotheses to explain the navigability of animals in weak magnetic fields, enabling e.g. birds to see the Earth's magnetic field. It also plays an essential role in the field of spin chemistry. Here, we show how quantum control can be used to either enhance or reduce the performance of such a chemical compass, providing a new route to further study the radical pair mechanism and its applications. We study the role of quantum entanglement in this mechanism, and demonstrate intriguing connections between radical-pair entanglement and the magnetic field sensitivity of the compass. Beyond their immediate application to the radical pair mechanism, these results also demonstrate how state-of-the-art quantum technologies could potentially be used to probe and control biological functions.Comment: 5 pages, 4 figures and supplementary material. Accepted by Phys. Rev. Lett

Simulation of reaction diffusion processes over biologically relevant size and time scales using multi-GPU workstations

AbstractSimulation of in vivo cellular processes with the reaction–diffusion master equation (RDME) is a computationally expensive task. Our previous software enabled simulation of inhomogeneous biochemical systems for small bacteria over long time scales using the MPD-RDME method on a single GPU. Simulations of larger eukaryotic systems exceed the on-board memory capacity of individual GPUs, and long time simulations of modest-sized cells such as yeast are impractical on a single GPU. We present a new multi-GPU parallel implementation of the MPD-RDME method based on a spatial decomposition approach that supports dynamic load balancing for workstations containing GPUs of varying performance and memory capacity. We take advantage of high-performance features of CUDA for peer-to-peer GPU memory transfers and evaluate the performance of our algorithms on state-of-the-art GPU devices. We present parallel efficiency and performance results for simulations using multiple GPUs as system size, particle counts, and number of reactions grow. We also demonstrate multi-GPU performance in simulations of the Min protein system in E. coli. Moreover, our multi-GPU decomposition and load balancing approach can be generalized to other lattice-based problems