We present moderately deep (125 ks) XMM-Newton observations of supernova remnant G330.2+1.0. This remnant is one of only a few known that fall into the "synchrotron-dominated" category, with the ...emission almost entirely dominated by a nonthermal continuum. Previous X-ray observations could only characterize the spectra of a few regions. Here, we examine the spectra from 14 regions surrounding the entire rim, finding that the spectral properties of the nonthermal emission do not vary significantly in any systematic way from one part of the forward shock to another, unlike several other remnants of this class. We confirm earlier findings that the power-law index, Γ, ranges from about 2.1-2.5, while the absorbing column density is generally between (2.0-2.6) × 1022 cm−2. Fits with the srcut model find values of the roll-off frequency in the range of 1017.1-1017.5 Hz, implying energies of accelerated electrons of ∼100 TeV. These values imply a high shock velocity of ∼4600 km s−1, favoring a young age of the remnant. Diffuse emission from the interior is nonthermal in origin as well, and fits to these regions yield similar values to those along the rim, also implying a young age. Thermal emission is present in the east, and the spectrum is consistent with a ∼650 km s−1 shock wave encountering interstellar or circumstellar material with a density of ∼1 cm−3.
ABSTRACT We present newly obtained X-ray and radio observations of Tycho's supernova remnant using Chandra and the Karl G. Jansky Very Large Array in 2015 and 2013/14, respectively. When combined ...with earlier epoch observations by these instruments, we now have time baselines for expansion measurements of the remnant of 12-15 years in the X-rays and 30 years in the radio. The remnant's large angular size allows for proper motion measurements at many locations around the periphery of the blast wave. Consistent with earlier measurements, we find a clear gradient in the expansion velocity of the remnant, despite its round shape. The proper motions on the western and southwestern sides of the remnant are about a factor of two higher than those in the east and northeast. We showed in an earlier work that this is related to an offset of the explosion site from the geometric center of the remnant due to a density gradient in the ISM, and using our refined measurements reported here, we find that this offset is ∼23″ toward the northeast. An explosion center offset in such a circular remnant has implications for searches for progenitor companions in other remnants.
We present the first 3D measurements of the velocity of various ejecta knots in Tycho's supernova remnant, known to result from a Type Ia explosion. Chandra X-ray observations over a 12 yr baseline ...from 2003 to 2015 allow us to measure the proper motion of nearly 60 "tufts" of Si-rich ejecta, giving us the velocity in the plane of the sky. For the line-of-sight velocity, we use two different methods: a nonequilibrium ionization model fit to the strong Si and S lines in the 1.2-2.8 keV regime, and a fit consisting of a series of Gaussian lines. These methods give consistent results, allowing us to determine the redshift or blueshift of each of the knots. Assuming a distance of 3.5 kpc, we find total velocities that range from 2400 to 6600 km s−1, with a mean of 4430 km s−1. We find several regions where the ejecta knots have overtaken the forward shock. These regions have proper motions in excess of 6000 km s−1. Some SN Ia explosion models predict a velocity asymmetry in the ejecta. We find no such velocity asymmetries in Tycho, and we discuss our findings in light of various explosion models, favoring those delayed-detonation models with relatively vigorous and symmetrical deflagrations. Finally, we compare measurements with models of the remnant's evolution that include both smooth and clumpy ejecta profiles, finding that both ejecta profiles can be accommodated by the observations.
Clinical observations and mouse models have suggested that inflammation can be pro-tumorigenic. Since chemokines are critical in leukocyte trafficking, we hypothesized that chemokines play essential ...roles in inflammation-associated cancers. Screening for 37 chemokines in prostate cancer cell lines and xenografts revealed CXCL16, the ligand for the receptor CXCR6, as the most consistently expressed chemokine. Immunohistochemistry and/or immunofluorescence and confocal imaging of 121 human prostate specimens showed that CXCL16 and CXCR6 were co-expressed, both on prostate cancer cells and adjacent T cells. Expression levels of CXCL16 and CXCR6 on cancer cells correlated with poor prognostic features including high-stage and high-grade, and expression also correlated with post-inflammatory changes in the cancer stroma as revealed by loss of alpha-smooth muscle actin. Moreover, CXCL16 enhanced the growth of CXCR6-expressing cancer and primary CD4 T cells. We studied expression of CXCL16 in an additional 461 specimens covering 12 tumor types, and found that CXCL16 was expressed in multiple human cancers associated with inflammation. Our study is the first to describe the expression of CXCL16/CXCR6 on both cancer cells and adjacent T cells in humans, and to demonstrate correlations between CXCL16 and CXCR6 vs. poor both prognostic features and reactive changes in cancer stoma. Taken together, our data suggest that CXCL16 and CXCR6 may mark cancers arising in an inflammatory milieu and mediate pro-tumorigenic effects of inflammation through direct effects on cancer cell growth and by inducing the migration and proliferation of tumor-associated leukocytes.
Tissues and organs are composed of distinct cell types that must operate in concert to perform physiological functions. Efforts to create high-dimensional biomarker catalogs of these cells have been ...largely based on single-cell sequencing approaches, which lack the spatial context required to understand critical cellular communication and correlated structural organization. To probe in situ biology with sufficient depth, several multiplexed protein imaging methods have been recently developed. Though these technologies differ in strategy and mode of immunolabeling and detection tags, they commonly utilize antibodies directed against protein biomarkers to provide detailed spatial and functional maps of complex tissues. As these promising antibody-based multiplexing approaches become more widely adopted, new frameworks and considerations are critical for training future users, generating molecular tools, validating antibody panels, and harmonizing datasets. In this Perspective, we provide essential resources, key considerations for obtaining robust and reproducible imaging data, and specialized knowledge from domain experts and technology developers.
Metal–organic framework nanoparticles (nanoMOFs) have been widely studied in biomedical applications. Although substantial efforts have been devoted to the development of biocompatible approaches, ...the requirement of tedious synthetic steps, toxic reagents, and limitations on the shelf life of nanoparticles in solution are still significant barriers to their translation to clinical use. In this work, we propose a new postsynthetic modification of nanoMOFs with phosphate-functionalized methoxy polyethylene glycol (mPEG–PO3) groups which, when combined with lyophilization, leads to the formation of redispersible solid materials. This approach can serve as a facile and general formulation method for the storage of bare or drug-loaded nanoMOFs. The obtained PEGylated nanoMOFs show stable hydrodynamic diameters, improved colloidal stability, and delayed drug-release kinetics compared to their parent nanoMOFs. Ex situ characterization and computational studies reveal that PEGylation of PCN-222 proceeds in a two-step fashion. Most importantly, the lyophilized, PEGylated nanoMOFs can be completely redispersed in water, avoiding common aggregation issues that have limited the use of MOFs in the biomedical field to the wet forma critical limitation for their translation to clinical use as these materials can now be stored as dried samples. The in vitro performance of the addition of mPEG–PO3 was confirmed by the improved intracellular stability and delayed drug-release capability, including lower cytotoxicity compared with that of the bare nanoMOFs. Furthermore, z-stack confocal microscopy images reveal the colocalization of bare and PEGylated nanoMOFs. This research highlights a facile PEGylation method with mPEG–PO3, providing new insights into the design of promising nanocarriers for drug delivery.
OH(1720 MHz) masers are excellent signposts of interaction between supernova remnants (SNRs) and molecular clouds. Using the Green Bank Telescope and Very Large Array we have surveyed 75 SNRs and six ...candidates for masers. Four SNRs are detected with OH masers: G5.4-1.2, G5.7-0.0, G8.7-0.1, and G9.7-0.0. Two SNRs, G5.7-0.0 and G8.7-0.1, have TeV g-ray counterparts which may indicate a local cosmic ray enhancement. It has been noted that maser-emitting (ME) SNRs are preferentially distributed in the molecular ring and nuclear disk. We use the present and existing surveys to demonstrate that masers are strongly confined to within |l| <= 50° at a rate of 15% of the total SNR population. All new detections are within 10° Galactic longitude emphasizing this trend. Additionally, a substantial number of SNR masers have peak fluxes at or below the detection threshold of existing surveys. This calls into question whether maser surveys of Galactic SNRs can be considered complete and how many ME remnants remain to be detected in the Galaxy.
Measurement of gene-expression profiles using microarray technology is becoming increasingly popular among the biomedical research community. Although there has been great progress in this field, ...investigators are still confronted with a difficult question after completing their experiments: how to validate the large data sets that are generated? This review summarizes current approaches to verifying global expression results, discusses the caveats that must be considered, and describes some methods that are being developed to address outstanding problems.
To evaluate declarative memory outcomes in medically refractory epilepsy patients who underwent either a highly selective laser ablation of the amygdalohippocampal complex or a conventional open ...temporal lobe resection.
Post-operative change scores were examined for verbal memory outcome in epilepsy patients who underwent stereotactic laser amygdalohippocampotomy (SLAH:
= 40) or open resection procedures (
= 40) using both reliable change index (RCI) scores and a 1-SD change metric.
Using RCI scores, patients undergoing open resection (12/40, 30.0%) were more likely to decline on verbal memory than those undergoing SLAH (2/40 5.0%,
= 0.0064, Fisher's exact test). Patients with language dominant procedures were much more likely to experience a significant verbal memory decline following open resection (9/19 47.4%) compared to laser ablation (2/19 10.5%,
= 0.0293, Fisher's exact test). 1 SD verbal memory decline frequently occurred in the open resection sample of language dominant temporal lobe patients with mesial temporal sclerosis (8/10 80.0%), although it rarely occurred in such patients after SLAH (2/14, 14.3%) (
= 0.0027, Fisher's exact test). Memory improvement occurred significantly more frequently following SLAH than after open resection.
These findings suggest that while verbal memory function can decline after laser ablation of the amygdalohippocampal complex, it is better preserved when compared to open temporal lobe resection. Our findings also highlight that the dominant hippocampus is not uniquely responsible for verbal memory. While this is at odds with our simple and common heuristic of the hippocampus in memory, it supports the findings of non-human primate studies showing that memory depends on broader medial and lateral TL regions.
Spitzer images of Tycho's supernova remnant in the mid-infrared reveal limb-brightened emission from the entire periphery of the shell and faint filamentary structures in the interior. As with other ...young remnants, this emission is produced by dust grains, warmed to ~100 K in the post-shock environment by collisions with energetic electrons and ions. The ratio of the 70 to 24 mum fluxes is a diagnostic of the dust temperature, which in turn is a sensitive function of the plasma density. We perform two-dimensional hydrodynamic simulations of a Type Ia supernova expanding into a density gradient in the ISM, and find that the overall round shape of the remnant is still easily achievable, even for explosions into significant gradients. The best match with hydrodynamical simulations is achieved if Tycho is located at a large distance in a medium with a mean preshock density of ~0.2 cmsup -3. Such preshock densities are obtained for highly (50%) porous ISM grains.
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