Updated Landscape of the Tumor Microenvironment and Targeting Strategies in an Era of Precision Medicine

Despite successive advances in clinical diagnosis and therapeutic intervention, cancer-associated morbidity and mortality keeps up with escalating cost to human society. Clinicians are confronted with an unprecedented challenge in curing cancers with de novo or acquired resistance. Failure to achieve effective and long-lasting treatment effects arises from the complexity of malignancies, particularly when plasticity of cancer cells is coupled with survival adaptability conferred by the pathologically co-opted stroma in the tumor microenvironment (TME). Targeting immune checkpoints, such as programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA4), provide significant benefit in multiple tumor types and produce substantial anticancer responses. Tissue resident stromal cells, although damaged together with cancer cells upon cytotoxic treatments, represent an ever-replenishing source that contributes to tumor restoration from residual cancer cells in the post-therapy stage. The TME displays a continually changing landscape, generating significant impacts on treatment outcome in clinics. Moving forward, implementing patient-specific analysis in clinical oncology with TME-oriented agents will significantly improve the specificity and efficacy of targeted therapies, thereby accelerating the translation of novel conceptions and groundbreaking discoveries in the TME biology through multiple bench-to-bed pipelines in current settings of precision cancer medicine

Climate variability of atmospheric rivers and droughts over the west coast of the united states from 2006 to 2019

Water resources are crucial to the livelihood and sustainability of the general public across the western United States. This study covers the timespan of both the third driest drought in Californian history between 2012 and 2015 as well as the extreme atmospheric river year in 2016-2017. The evaluation of vertical moisture profiles using Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) Radio Occultation (RO) data, National Centers for Environmental Prediction (NCEP)/National Center for Atmospheric Research (NCAR) Reanalysis of 500 hPa geopotential heights, 1000-500 hPa thickness, Optimum Interpolation (OI) Sea Surface Temperature (SST), NOAA/NDBC buoy data, and NASA, MEaSUREs, Gridded Sea Surface Height Anomalies (SSHA) were performed. The daily COSMIC time evolution from 2006 through 2015 showed a flat to slightly upward trend of both temperature and water vapor profiles through the entirety of the western US drought. Subsequently, a significant increase of temperatures and water vapor were recorded in early 2016 before the extreme Atmospheric River (AR) season of 2016-2017. The quantitative analyses suggest that warmer SST and higher SSHA lead to an increase of heat fluxes from the ocean into the troposphere, which forces thickness changes and thus the position of troughs in the geopotential height field changes afterwards, consequently pushing the trough eastward over the Pacific Northwest and potentially leading to an active AR year in the western US. It appears that regional COSMIC RO moisture profiles, seasonal SST, and SLH anomalies may serve as a precursor for seasonal or sub-seasonal precipitation outlook along the western US

Temporal variability of the telluric sodium layer

The temporal variability of the telluric sodium layer is investigated by analyzing 28 nights of data obtained with the Colorado State University LIDAR experiment. The mean height power spectrum of the sodium layer was found to be well fit by a power law over the observed range of frequencies, 10 microhertz to 4 millhertz. The best fitting power law was found to be 10^\beta \nu^\alpha, with \alpha = -1.79 +/- 0.02 and \beta = 1.12 +/- 0.40. Applications to wavefront sensing require knowledge of the behavior of the sodium layer at kHz frequencies. Direct measurements at these frequencies do not exist. Extrapolation from low-frequency behavior to high frequencies suggests that this variability may be a significant source of error for laser-guide-star adaptive optics on large-aperture telescopes.Comment: 3 pages, 3 figures, accepted for publication in Optics Letter

Can a charged ring levitate a neutral, polarizable object? Can Earnshaw's Theorem be extended to such objects?

Stable electrostatic levitation and trapping of a neutral, polarizable object by a charged ring is shown to be theoretically impossible. Earnshaw's Theorem precludes the existence of such a stable, neutral particle trap.Comment: 11 pages, 1 figur

Recombinant Thrombomodulin Has an Antitumor Effect and Enhances the Sensitivity of Gemcitabine Treatment of Pancreatic Cancer via G-protein Coupled Receptor 15

https://openworks.mdanderson.org/sumexp21/1223/thumbnail.jp

Smartphone-based vase design: a developing creative practice

peer-reviewedThis article describes a developing creative practice whereby digital creative processes adapted from mobile music making are used in the data driven design and subsequent digital instantiation of ceramic vessels. First, related work in mobile music creation and recent developments in the digital design and fabrication of ceramics frames the research and puts it in a broad context. A pilot study is then detailed, concluding that although largely successful, a number of areas of the process needed to be improved and refined. The results of a further iteration of the process, consisting of the digital creation and instantiation of location-specific vessels is presented, before the current state of the research, where ceramic vessels are 3D printed, is outlined. We show that mobile phones can become integral to a practical design process that allows the digital forms it creates to be instantiated using 3D printing, and that these become high-quality, end-use artefacts. The final section discusses what has been learned and contemplates how the described practice will be developed yet further

Disruption of the NF-κB/IκBα Autoinhibitory Loop Improves Cognitive Performance and Promotes Hyperexcitability of Hippocampal Neurons

<p>Abstract</p> <p>Background</p> <p>Though originally discovered in the immune system as an important mediator of inflammation, NF-κB has recently been shown to play key roles in the central nervous system, such as synaptogenesis, synaptic plasticity, and cognition. NF-κB activity is normally tightly regulated by its primary inhibitor, IκBα, through a unique autoinhibitory loop. In this study, we tested the hypothesis that the IκBα autoinhibitory loop ensures optimal levels of NF-κB activity to promote proper brain development and function. To do so, we utilized knock-in mice which possess mutations in the IκBα promoter to disrupt the autoinhibitory loop (IκBα^M/MKI mice).</p> <p>Results</p> <p>Here, we show that these mutations delay IκBα resynthesis and enhance NF-κB activation in neurons following acute activating stimuli. This leads to improved cognitive ability on tests of hippocampal-dependent learning and memory but no change in hippocampal synaptic plasticity. Instead, hippocampal neurons from IκBα^M/MKI mice form more excitatory and less inhibitory synapses in dissociated cultures and are hyperexcitable. This leads to increased burst firing of action potentials and the development of abnormal hypersynchronous discharges <it>in vivo</it>.</p> <p>Conclusions</p> <p>These results demonstrate that the IκBα autoinhibitory loop is critical for titrating appropriate levels of endogenous NF-κB activity to maintain proper neuronal function.</p

Demonstration of images with negative group velocities

We report the experimental demonstration of the superluminal propagation of multi-spatial-mode images via four-wave mixing in hot atomic vapor, in which all spatial sub-regions propagate with negative group velocities. We investigate the spatial mode properties and temporal reshaping of the fast light images, and show large relative pulse peak advancements of up to 64% of the input pulse width. The degree of temporal reshaping is quantified and increases as the relative pulse peak advancement increases. When optimized for image quality or pulse advancement, negative group velocities of up to $v_{g}=-\frac{c}{880}$ and $v_{g}=-\frac{c}{2180}$, respectively, are demonstrated when integrating temporally over the entire image. The present results are applicable to temporal cloaking devices that require strong manipulation of the dispersion relation, where one can envision temporally cloaking various spatial regions of an image for different durations. Additionally, the modes involved in a four-wave mixing process similar to the present experiment have been shown to exhibit quantum correlations and entanglement. The results presented here provide insight into how to tailor experimental tests of the behavior of these quantum correlations and entanglement in the superluminal regime.Comment: 9 pages, 4 figure

Focus errors from tracking sodium layer altitude variations with laser guide star adaptive optics for the Thirty Meter Telescope

Laser guide star (LGS) adaptive optics systems for extremely large telescopes must handle an important effect that is negligible for current generation telescopes. Wavefront errors, due to improperly focusing laser wavefront sensors (WFS) on the mesospheric sodium layer, are proportional to the square of the telescope diameter. The sodium layer, whose mean altitude is approximately 90 km, can move vertically at rates of up to a few metres per second; a few seconds lag in refocusing can substantially degrade delivered image quality (15 m of defocus can cause 120 nm residual wavefront error on a 30-m telescope.) As well, the range of temporal frequencies of sodium altitude focus, overlaps the temporal frequencies of focus caused by atmospheric turbulence. Only natural star wavefront sensors can disentangle this degeneracy. However, applying corrections with representative focus mechanisms having modest control bandwidths causes appreciable tracking errors. In principle, electronic offsets measured by natural guide star detectors could be rapidly applied to laser WFS measurements, but to provide useable sky coverage, integrating sufficient photons causes an unavoidable time delay, again resulting in potentially serious focus tracking errors. However, our analysis depends on extrapolating to temporal frequencies greater than 1 Hz from power spectra of sodium profile time series taken at 1-2 minute intervals. In principle, with a pulsed laser, (e.g. 3-μs pulses) and dynamic refocusing on a polar-coordinate CCD, this focus tracking error may be eliminated. This result is an additional benefit of dynamic refocusing beyond the commonly recognized amelioration of LGS WFS spot elongation