COVID-19 and Cancer: Current Challenges and Perspectives.

Patients with cancer have been disproportionately affected by the COVID-19 pandemic. This effect has included the adverse outcomes in patients with cancer who develop COVID-19, the impact of the COVID-19 pandemic on the delivery of cancer care, and the severe disruption to cancer research. However, patients with cancer are a heterogeneous population, and recent studies have now documented factors that allow risk stratification of patients with cancer in order to optimize care. In this review, we highlight data at the intersection of COVID-19 and cancer, including the biological interplay between the two diseases and practical recommendations for the treatment of patients with cancer during the pandemic. We additionally discuss the potential long-lasting impact of the pandemic on cancer care due to its deleterious effect on cancer research, as well as biological insights from the cancer research community that could help develop novel therapies for all patients with COVID-19

Photonic band structure of highly deformable, self-assembling systems

We calculate the photonic band structure at normal incidence of highly deformable, self-assembling systems - cholesteric elastomers subjected to external stress. Cholesterics display brilliant reflection and lasing owing to gaps in their photonic band structure. The band structure of cholesteric elastomers varies sensitively with strain, showing new gaps opening up and shifting in frequency. A novel prediction of a total band gap is made, and is expected to occur in the vicinity of the previously observed de Vries bandgap, which is only for one polarisation

Overcoming adaptive resistance in mucoepidermoid carcinoma through inhibition of the IKK-β/IκBα/NFκB axis

Patients with mucoepidermoid carcinoma (MEC) experience low survival rates and high morbidity following treatment, yet the intrinsic resistance of MEC cells to ionizing radiation (IR) and the mechanisms underlying acquired resistance remain unexplored. Herein, we demonstrated that low doses of IR intrinsically activated NFκB in resistant MEC cell lines. Moreover, resistance was significantly enhanced in IR-sensitive cell lines when NFκB pathway was stimulated. Pharmacological inhibition of the IKK-β/IκBα/ NFκB axis, using a single dose of FDA-approved Emetine, led to a striking sensitization of MEC cells to IR and a reduction in cancer stem cells. We achieved a major step towards better understanding the basic mechanisms involved in IR-adaptive resistance in MEC cell lines and how to efficiently overcome this critical problem

The Pt isotopes: comparing the Interacting Boson Model with Configuration Mixing and the Extended Consistent-Q formalism

The role of intruder configurations in the description of energy spectra and B(E2) values in the Pt region is analyzed. In particular, we study the differences between Interacting Boson Model calculations with or without the inclusion of intruder states in the even Pt nuclei $^{172-194}$Pt. As a result, it shows that for the description of a subset of the existing experimental data, i.e., energy spectra and absolute B(E2) values up to an excitation energy of about 1.5 MeV, both approaches seem to be equally valid. We explain these similarities between both model spaces through an appropriate mapping. We point out the need for a more extensive comparison, encompassing a data set as broad (and complete) as possible to confront with both theoretical approaches in order to test the detailed structure of the nuclear wave functions.Comment: To be published in NP

States and transitions in black-hole binaries

With the availability of the large database of black-hole transients from the Rossi X-Ray Timing Explorer, the observed phenomenology has become very complex. The original classification of the properties of these systems in a series of static states sorted by mass accretion rate proved not to be able to encompass the new picture. I outline here a summary of the current situation and show that a coherent picture emerges when simple properties such as X-ray spectral hardness and fractional variability are considered. In particular, fast transition in the properties of the fast time variability appear to be crucial to describe the evolution of black-hole transients. Based on this picture, I present a state-classification which takes into account the observed transitions. I show that, in addition to transients systems, other black-hole binaries and Active Galactic Nuclei can be interpreted within this framework. The association between these states and the physics of the accretion flow around black holes will be possible only through modeling of the full time evolution of galactic transient systems.Comment: 30 pages, 11 figures, To appear in Belloni, T. (ed.): The Jet Paradigm - From Microquasars to Quasars, Lect. Notes Phys. 794 (2009

Forced oscillations in a hydrodynamical accretion disk and QPOs

This is the second of a series of papers aimed to look for an explanation on the generation of high frequency quasi-periodic oscillations (QPOs) in accretion disks around neutron star, black hole, and white dwarf binaries. The model is inspired by the general idea of a resonance mechanism in the accretion disk oscillations as was already pointed out by Abramowicz & Klu{\'z}niak (\cite{Abramowicz2001}). In a first paper (P\'etri \cite{Petri2005a}, paper I), we showed that a rotating misaligned magnetic field of a neutron star gives rise to some resonances close to the inner edge of the accretion disk. In this second paper, we suggest that this process does also exist for an asymmetry in the gravitational potential of the compact object. We prove that the same physics applies, at least in the linear stage of the response to the disturbance in the system. This kind of asymmetry is well suited for neutron stars or white dwarfs possessing an inhomogeneous interior allowing for a deviation from a perfectly spherically symmetric gravitational field. We show by a linear analysis that the disk initially in a cylindrically symmetric stationary state is subject to three kinds of resonances: a corotation resonance, a Lindblad resonance due to a driven force and a parametric sonance. The highest kHz QPOs are then interpreted as the orbital frequency of the disk at locations where the response to the resonances are maximal. It is also found that strong gravity is not required to excite the resonances.Comment: Accepte

Measuring Black Hole Spin using X-ray Reflection Spectroscopy

I review the current status of X-ray reflection (a.k.a. broad iron line) based black hole spin measurements. This is a powerful technique that allows us to measure robust black hole spins across the mass range, from the stellar-mass black holes in X-ray binaries to the supermassive black holes in active galactic nuclei. After describing the basic assumptions of this approach, I lay out the detailed methodology focusing on "best practices" that have been found necessary to obtain robust results. Reflecting my own biases, this review is slanted towards a discussion of supermassive black hole (SMBH) spin in active galactic nuclei (AGN). Pulling together all of the available XMM-Newton and Suzaku results from the literature that satisfy objective quality control criteria, it is clear that a large fraction of SMBHs are rapidly-spinning, although there are tentative hints of a more slowly spinning population at high (M>5*10^7Msun) and low (M<2*10^6Msun) mass. I also engage in a brief review of the spins of stellar-mass black holes in X-ray binaries. In general, reflection-based and continuum-fitting based spin measures are in agreement, although there remain two objects (GROJ1655-40 and 4U1543-475) for which that is not true. I end this review by discussing the exciting frontier of relativistic reverberation, particularly the discovery of broad iron line reverberation in XMM-Newton data for the Seyfert galaxies NGC4151, NGC7314 and MCG-5-23-16. As well as confirming the basic paradigm of relativistic disk reflection, this detection of reverberation demonstrates that future large-area X-ray observatories such as LOFT will make tremendous progress in studies of strong gravity using relativistic reverberation in AGN.Comment: 19 pages. To appear in proceedings of the ISSI-Bern workshop on "The Physics of Accretion onto Black Holes" (8-12 Oct 2012). Revised version adds a missing source to Table 1 and Fig.6 (IRAS13224-3809) and corrects the referencing of the discovery of soft lags in 1H0707-495 (which were in fact first reported in Fabian et al. 2009

Inorganic concepts relevant to metal binding, activity, and toxicity in a biological system

The purpose of this paper is to review selected physical and inorganic concepts and factors which might be important in assessing and/or understanding the fact and disposition of a metal system in a biological environment. Hopefully, such inquiries will ultimately permit us to understand, rationalize, and predict differences and trends in biological effects as a function of the basic nature of a metal system and, in optimal cases, serve as input to a system of guidelines for the notion of Chemical Dosimetry.'' The plan of this paper is to first review, in general terms, the basic principles of the Crystal Field Theory (CFT), a unifying theory of bonding in metal complexes. This will provide the necessary theoretical background for the subsequent discussion of selected concepts and factors. 21 refs., 7 figs., 6 tabs

Endothelial-derived interleukin-6 induces cancer stem cell motility by generating a chemotactic gradient towards blood vessels

Recent evidence suggests that the metastatic spread of head and neck squamous cell carcinomas (HNSCC) requires the function of cancer stem cells endowed with multipotency, self-renewal, and high tumorigenic potential. We demonstrated that cancer stem cells reside in perivascular niches and are characterized by high aldehyde dehydrogenase (ALDH) activity and high CD44 expression (ALDHhighCD44high) in HNSCC. Here, we hypothesize that endothelial cell-secreted interleukin-6 (IL-6) contributes to tumor progression by enhancing the migratory phenotype and survival of cancer stem cells. Analysis of tissue microarrays generated from the invasive fronts of 77 HNSCC patients followed-up for up to 11 years revealed that high expression of IL-6 receptor (IL-6R) (p=0.0217) or co-receptor gp130 (p=0.0422) correlates with low HNSCC patient survival. We observed that endothelial cell-secreted factors induce epithelial to mesenchymal transition (EMT) and enhance invasive capacity of HNSCC cancer stem cells. Conditioned medium from CRISPR/Cas9-mediated IL-6 knockout primary human endothelial cells is less chemotactic for cancer stem cells in a microfluidics-based system than medium from control endothelial cells (p < 0.05). Blockade of the IL-6 pathway with a humanized anti-IL-6R antibody (tocilizumab) inhibited endothelial cell-induced motility in vitro and decreased the fraction of cancer stem cells in vivo. Notably, xenograft HNSCC tumors vascularized with IL-6-knockout endothelial cells exhibited slower tumor growth and smaller cancer stem cell fraction. These findings demonstrate that endothelial cell-secreted IL-6 enhances the motility and survival of highly tumorigenic cancer stem cells, suggesting that endothelial cells can create a chemotactic gradient that enables the movement of carcinoma cells towards blood vessels

Accretion, Outflows, and Winds of Magnetized Stars

Many types of stars have strong magnetic fields that can dynamically influence the flow of circumstellar matter. In stars with accretion disks, the stellar magnetic field can truncate the inner disk and determine the paths that matter can take to flow onto the star. These paths are different in stars with different magnetospheres and periods of rotation. External field lines of the magnetosphere may inflate and produce favorable conditions for outflows from the disk-magnetosphere boundary. Outflows can be particularly strong in the propeller regime, wherein a star rotates more rapidly than the inner disk. Outflows may also form at the disk-magnetosphere boundary of slowly rotating stars, if the magnetosphere is compressed by the accreting matter. In isolated, strongly magnetized stars, the magnetic field can influence formation and/or propagation of stellar wind outflows. Winds from low-mass, solar-type stars may be either thermally or magnetically driven, while winds from massive, luminous O and B type stars are radiatively driven. In all of these cases, the magnetic field influences matter flow from the stars and determines many observational properties. In this chapter we review recent studies of accretion, outflows, and winds of magnetized stars with a focus on three main topics: (1) accretion onto magnetized stars; (2) outflows from the disk-magnetosphere boundary; and (3) winds from isolated massive magnetized stars. We show results obtained from global magnetohydrodynamic simulations and, in a number of cases compare global simulations with observations.Comment: 60 pages, 44 figure