Current Management Strategy of Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma is an unique head and neck cancer. It is common among the southern Chinese and is closely associated with the Epstein Barr virus (EBV). To diagnose the disease in its early stage is infrequent as the symptoms are usually trivial and patients only present in late stages. Testing the blood for elevated EBV DNA has now become a screening test for the high risk group of patients, aiming to diagnose the disease in its early stages. Imaging studies, positron emission tomography scans in addition to clinical examination provide information on the extent of the disease. The confirmation of the disease still depends on endoscopic examination and biopsy. Radiotherapy with or without chemotherapy has been the primary treatment modality. The application of intensity modulated radiotherapy and the use of concomitant chemoradiation have improved the control of nasopharyngeal carcinoma together with the reduction of long term side effects. The early detection of residual or recurrence tumor in the neck or at the primary site has allowed delivery of salvage treatment. The choice of the optimal surgical salvage, either for neck disease or primary tumor depends on the extent of the residual or recurrent disease. The outcome of these patients have improved with the application of the appropriate surgical salvage

Both Ca2+ and Zn2+ are essential for S100A12 protein oligomerization and function

Background Human S100A12 is a member of the S100 family of EF-hand calcium-modulated proteins that are associated with many diseases including cancer, chronic inflammation and neurological disorders. S100A12 is an important factor in host/parasite defenses and in the inflammatory response. Like several other S100 proteins, it binds zinc and copper in addition to calcium. Mechanisms of zinc regulation have been proposed for a number of S100 proteins e.g. S100B, S100A2, S100A7, S100A8/9. The interaction of S100 proteins with their targets is strongly dependent on cellular microenvironment. Results The aim of the study was to explore the factors that influence S100A12 oligomerization and target interaction. A comprehensive series of biochemical and biophysical experiments indicated that changes in the concentration of calcium and zinc led to changes in the oligomeric state of S100A12. Surface plasmon resonance confirmed that the presence of both calcium and zinc is essential for the interaction of S100A12 with one of its extracellular targets, RAGE – the Receptor for Advanced Glycation End products. By using a single-molecule approach we have shown that the presence of zinc in tissue culture medium favors both the oligomerization of exogenous S100A12 protein and its interaction with targets on the cell surface. Conclusion We have shown that oligomerization and target recognition by S100A12 is regulated by both zinc and calcium. Our present work highlighted the potential role of calcium-binding S100 proteins in zinc metabolism and, in particular, the role of S100A12 in the cross talk between zinc and calcium in cell signaling

Enzyme-Responsive Snap-Top Covered Silica Nanocontainers

Mesoporous silica nanoparticles, capable of storing a payload of small molecules and releasing it following specific catalytic activation by an esterase, have been designed and fabricated. The storage and release of the payload is controlled by the presence of [2]rotaxanes, which consist of tri(ethylene glycol) chains threaded by α-cyclodextrin tori, located on the surfaces of the nanoparticles and terminated by a large stoppering group. These modified silica nanoparticles are capable of encapsulating guest molecules when the [2]rotaxanes are present. The bulky stoppers, which serve to hold the tori in place, are stable under physiological conditions but are cleaved by the catalytic action of an enzyme, causing dethreading of the tori and release of the guest molecules from the pores of the nanoparticles. These snap-top covered silica nanocontainers (SCSNs) are prepared by a modular synthetic method, in which the stoppering unit, incorporated in the final step of the synthesis, may be changed at will to target the response of the system to any of a number of hydrolytic enzymes. Here, the design, synthesis, and operation of model SCSNs that open in the presence of porcine liver esterase (PLE) are reported. The empty pores of the silica nanoparticles were loaded with luminescent dye molecules (rhodamine B), and stoppering units that incorporate adamantyl ester moieties were then attached in the presence of α-cyclodextrin using the copper-catalyzed azide−alkyne cycloaddition (CuAAC), closing the SCSNs. The release of rhodamine-B from the pores of the SCSN, following PLE-mediated hydrolysis of the stoppers, was monitored using fluorescence spectroscopy

Quasars and the Big Blue Bump

We investigate the ultraviolet-to-optical spectral energy distributions (SEDs) of 17 active galactic nuclei (AGNs) using quasi-simultaneous spectrophotometry spanning 900-9000 Angstrom (rest frame). We employ data from the Far Ultraviolet Spectroscopic Explorer (FUSE), the Hubble Space Telescope (HST), and the 2.1-meter telescope at Kitt Peak National Observatory (KPNO). Taking advantage of the short-wavelength coverage, we are able to study the so-called "big blue bump," the region where the energy output peaks, in detail. Most objects exhibit a spectral break around 1100 Angstrom. Although this result is formally associated with large uncertainty for some objects, there is strong evidence in the data that the far-ultraviolet spectral region is below the extrapolation of the near-ultraviolet-optical slope, indicating a spectral break around 1100 Angstrom. We compare the behavior of our sample to those of non-LTE thin-disk models covering a range in black-hole mass, Eddington ratio, disk inclination, and other parameters. The distribution of ultraviolet-optical spectral indices redward of the break, and far-ultraviolet indices shortward of the break, are in rough agreement with the models. However, we do not see a correlation between the far-ultraviolet spectral index and the black hole mass, as seen in some accretion disk models. We argue that the observed spectral break is intrinsic to AGNs, although intrinsic reddening as well as Comptonization can strongly affect the far-ultraviolet spectral index. We make our data available online in digital format.Comment: 32 pages (10pt), 12 figures. Accepted for publication in Ap

Calcium/calmodulin-dependent kinase kinase 2 regulates hematopoietic stem and progenitor cell regeneration

Hematopoietic stem and progenitor cells (HSPCs) are predominantly quiescent in adults, but proliferate in response to bone marrow (BM) injury. Here, we show that deletion of Ca2+/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) promotes HSPC regeneration and hematopoietic recovery following radiation injury. Using Camkk2-enhanced green fluorescent protein (EGFP) reporter mice, we found that Camkk2 expression is developmentally regulated in HSPC. Deletion of Camkk2 in HSPC results in a significant downregulation of genes affiliated with the quiescent signature. Accordingly, HSPC from Camkk2 null mice have a high proliferative capability when stimulated in vitro in the presence of BM-derived endothelial cells. In addition, Camkk2 null mice are more resistant to radiation injury and show accelerated hematopoietic recovery, enhanced HSPC regeneration and ultimately a prolonged survival following sublethal or lethal total body irradiation. Mechanistically, we propose that CaMKK2 regulates the HSPC response to hematopoietic damage by coupling radiation signaling to activation of the anti-proliferative AMP-activated protein kinase. Finally, we demonstrated that systemic administration of the small molecule CaMKK2 inhibitor, STO-609, to irradiated mice enhanced HSPC recovery and improved survival. These findings identify CaMKK2 as an important regulator of HSPC regeneration and demonstrate CaMKK2 inhibition is a novel approach to promoting hematopoietic recovery after BM injury

The global response : how cities and provinces around the globe tackled COVID-19 outbreaks in 2021—authors’ reply

We would like to thank Ngo et al., for expressing their interest in our work. In our recent work, we looked at the preventive measures that were undertaken by various cities and provinces across the globe to prevent the spread of COVID-19 infection. In their correspondence, Ngo et al., have raised potential concerns in association with the data presented and certain definitions used in the paper. Upon receipt of their letter, we revisited our data sources. Herein, we provide a point-by-point response to the concerns raised by Ngo et al

Towards graphane field emitters.

We report on the improved field emission performance of graphene foam (GF) following transient exposure to hydrogen plasma. The enhanced field emission mechanism associated with hydrogenation has been investigated using Fourier transform infrared spectroscopy, plasma spectrophotometry, Raman spectroscopy, and scanning electron microscopy. The observed enhanced electron emissionhas been attributed to an increase in the areal density of lattice defects and the formation of a partially hydrogenated, graphane-like material. The treated GF emitter demonstrated a much reduced macroscopic turn-on field (2.5 V μm-1), with an increased maximum current density from 0.21 mA cm-2 (pristine) to 8.27 mA cm-2 (treated). The treated GFs vertically orientated protrusions, after plasma etching, effectively increased the local electric field resulting in a 2.2-fold reduction in the turn-on electric field. The observed enhancement is further attributed to hydrogenation and the subsequent formation of a partially hydrogenated structured 2D material, which advantageously shifts the emitter work function. Alongside augmentation of the nominal crystallite size of the graphitic superstructure, surface bound species are believed to play a key role in the enhanced emission. The hydrogen plasma treatment was also noted to increase the emission spatial uniformity, with an approximate four times reduction in the per unit area variation in emission current density. Our findings suggest that plasma treatments, and particularly hydrogen and hydrogen-containing precursors, may provide an efficient, simple, and low cost means of realizing enhanced nanocarbon-based field emission devices via the engineered degradation of the nascent lattice, and adjustment of the surface work function.For assistance in ATR FTIR and EDXRF measurements we thank Dr Bob Keighley and Dr Ralph Vokes of Shimadzu Corp; and for plasma optical spectrophotometry analysis, Dr Thomas Schűtte of PLASUS GmbH. This work is supported by National Key Basic Research Program 973(2010CB327705), National Natural Science Foundation Project (51120125001, 51002031, 61101023, 51202028), Foundation of Doctoral Program of Ministry of Education (20100092110015), an EPSRC Impact Acceleration grant, and the Research Fund for International Young Scientists from NSFC (510501101 42, 51350110232). MT Cole thanks the Oppenheimer Trust for their generous financial support.This is the author accepted manuscript. The final version is available from the Royal Society of Chemistry via http://dx.doi.org/10.1039/C5RA20771

Towards graphane field emitters

We report on the improved field emission performance of graphene foam (GF) following transient exposure to hydrogen plasma. The enhanced field emission mechanism associated with hydrogenation has been investigated using Fourier transform infrared spectroscopy, plasma spectrophotometry, Raman spectroscopy, and scanning electron microscopy. The observed enhanced electron emissionhas been attributed to an increase in the areal density of lattice defects and the formation of a partially hydrogenated, graphane-like material. The treated GF emitter demonstrated a much reduced macroscopic turn-on field (2.5 V μm-1), with an increased maximum current density from 0.21 mA cm-2 (pristine) to 8.27 mA cm-2 (treated). The treated GFs vertically orientated protrusions, after plasma etching, effectively increased the local electric field resulting in a 2.2-fold reduction in the turn-on electric field. The observed enhancement is further attributed to hydrogenation and the subsequent formation of a partially hydrogenated structured 2D material, which advantageously shifts the emitter work function. Alongside augmentation of the nominal crystallite size of the graphitic superstructure, surface bound species are believed to play a key role in the enhanced emission. The hydrogen plasma treatment was also noted to increase the emission spatial uniformity, with an approximate four times reduction in the per unit area variation in emission current density. Our findings suggest that plasma treatments, and particularly hydrogen and hydrogen-containing precursors, may provide an efficient, simple, and low cost means of realizing enhanced nanocarbon-based field emission devices via the engineered degradation of the nascent lattice, and adjustment of the surface work function.</p

A dynamical model reveals gene co-localizations in nucleus

Co-localization of networks of genes in the nucleus is thought to play an important role in determining gene expression patterns. Based upon experimental data, we built a dynamical model to test whether pure diffusion could account for the observed co-localization of genes within a defined subnuclear region. A simple standard Brownian motion model in two and three dimensions shows that preferential co-localization is possible for co-regulated genes without any direct interaction, and suggests the occurrence may be due to a limitation in the number of available transcription factors. Experimental data of chromatin movements demonstrates that fractional rather than standard Brownian motion is more appropriate to model gene mobilizations, and we tested our dynamical model against recent static experimental data, using a sub-diffusion process by which the genes tend to colocalize more easily. Moreover, in order to compare our model with recently obtained experimental data, we studied the association level between genes and factors, and presented data supporting the validation of this dynamic model. As further applications of our model, we applied it to test against more biological observations. We found that increasing transcription factor number, rather than factory number and nucleus size, might be the reason for decreasing gene co-localization. In the scenario of frequency-or amplitude-modulation of transcription factors, our model predicted that frequency-modulation may increase the co-localization between its targeted genes

Discovery of Two Distant Type Ia Supernovae in the Hubble Deep Field North with the Advanced Camera for Surveys

We present observations of the first two supernovae discovered with the recently installed Advanced Camera for Surveys (ACS) on the Hubble Space Telescope. The supernovae were found in Wide Field Camera images of the Hubble Deep Field North taken with the F775W, F850LP, and G800L optical elements as part of the ACS guaranteed time observation program. Spectra extracted from the ACS G800L grism exposures confirm that the objects are Type Ia supernovae (SNe Ia) at redshifts z=0.47 and z=0.95. Follow-up HST observations have been conducted with ACS in F775W and F850LP and with NICMOS in the near-infrared F110W bandpass, yielding a total of 9 flux measurements in the 3 bandpasses over a period of 50 days in the observed frame. We discuss many of the important issues in doing accurate photometry with the ACS. We analyze the multi-band light curves using two different fitting methods to calibrate the supernovae luminosities and place them on the SNe Ia Hubble diagram. The resulting distances are consistent with the redshift-distance relation of the accelerating universe model, although evolving intergalactic grey dust remains as a less likely possibility. The relative ease with which these SNe Ia were found, confirmed, and monitored demonstrates the potential ACS holds for revolutionizing the field of high-redshift SNe Ia, and therefore of testing the accelerating universe cosmology and constraining the "epoch of deceleration".Comment: 11 pages, 8 embedded figures. Accepted for publication in Ap