Exploring the impact of vibrational cavity coupling strength on ultrafast CN + cc-C6_6H12_{12} reaction dynamics

Molecular polaritons, hybrid light-matter states resulting from strong cavity coupling of optical transitions, may provide a new route to guide chemical reactions. However, demonstrations of cavity-modified reactivity in clean benchmark systems are still needed to clarify the mechanisms and scope of polariton chemistry. Here, we use transient absorption to observe the ultrafast dynamics of CN radicals interacting with a cyclohexane ($c$-C$_6$H$_{12}$) and chloroform (CHCl$_3$) solvent mixture under vibrational strong coupling of the brightest C$-$H stretching mode of $c$-C$_6$H$_{12}$. By modulating the $c$-C$_6$H$_{12}$:CHCl$_3$ ratio, we explore how solvent complexation and hydrogen (H)-abstraction processes proceed under collective cavity coupling strengths ranging from 55$-$85 cm$^{-1}$. Reaction rates remain unchanged for all extracavity, on resonance, and off-resonance cavity coupling conditions, regardless of coupling strength. These results suggest that insufficient vibrational cavity coupling strength may not be the determining factor for the negligible cavity effects observed previously in H-abstraction reactions of CN with CHCl$_3$

TGF-Beta suppresses VEGFA-mediated angiogenesis in colon cancer metastasis.

The FET cell line, derived from an early stage colon carcinoma, is non-tumorigenic in athymic nude mice. Engineered FET cells that express TGF-α (FETα) display constitutively active EGFR/ErbB signaling. These cells readily formed xenograft tumors in athymic nude mice. Importantly, FETα cells retained their response to TGF-beta-mediated growth inhibition, and, like the parental FET cells, expression of a dominant negative TGF-beta type II receptor (DNRII) in FETα cells (FETα/DNRII) abrogated responsiveness to TGF-beta-induced growth inhibition and apoptosis under stress conditions in vitro and increased metastatic potential in an orthotopic model in vivo, which indicates metastasis suppressor activity of TGF-beta signaling in this model. Cancer angiogenesis is widely regarded as a key attribute for tumor formation and progression. Here we show that TGF-beta signaling inhibits expression of vascular endothelial growth factor A (VEGFA) and that loss of autocrine TGF-beta in FETα/DNRII cells resulted in increased expression of VEGFA. Regulation of VEGFA expression by TGF-beta is not at the transcriptional level but at the post-transcriptional level. Our results indicate that TGF-beta decreases VEGFA protein stability through ubiquitination and degradation in a PKA- and Smad3-dependent and Smad2-independent pathway. Immunohistochemical (IHC) analyses of orthotopic tumors showed significantly reduced TGF-beta signaling, increased CD31 and VEGFA staining in tumors of FETα/DNRII cells as compared to those of vector control cells. These results indicate that inhibition of TGF-beta signaling increases VEGFA expression and angiogenesis, which could potentially contribute to enhanced metastasis of those cells in vivo. IHC studies performed on human colon adenocarcinoma specimens showed that TGF-beta signaling is inversely correlated with VEGFA expression, indicating that TGF-beta-mediated suppression of VEGFA expression exists in colon cancer patients

Ultrafast dynamics of CN radical reactions with chloroform solvent under vibrational strong coupling

Polariton chemistry may provide a new means to control molecular reactivity, permitting remote, reversible modification of reaction energetics, kinetics, and product yields. A considerable body of experimental and theoretical work has already demonstrated that strong coupling between a molecular vibrational mode and the confined electromagnetic field of an optical cavity can alter chemical reactivity without external illumination. However, the mechanisms underlying cavity-altered chemistry remain unclear in large part because the experimental systems examined previously are too complex for detailed analysis of their reaction dynamics. Here, we experimentally investigate photolysis-induced reactions of cyanide (CN) radicals with strongly-coupled chloroform (CHCl$_3$) solvent molecules and examine the intracavity rates of photofragment recombination, solvent complexation, and hydrogen abstraction. We use a microfluidic optical cavity fitted with dichroic mirrors to facilitate vibrational strong coupling (VSC) of the C-H stretching mode of CHCl$_3$ while simultaneously permitting optical access at visible wavelengths. Ultrafast transient absorption experiments performed with cavities tuned on- and off-resonance reveal that VSC of the CHCl$_3$ C-H stretching transition does not significantly modify any measured rate constants, including those associated with the hydrogen abstraction reaction. This work represents, to the best of our knowledge, the first experimental study of an elementary bimolecular reaction under VSC. We discuss how the conspicuous absence of cavity-altered effects in this system may provide insights into the mechanisms of modified ground state reactivity under VSC and help bridge the divide between experimental results and theoretical predictions in vibrational polariton chemistry

Semicontinuous Bioreactor Production of Recombinant Butyrylcholinesterase in Transgenic Rice Cell Suspension Cultures.

An active and tetrameric form of recombinant butyrylcholinesterase (BChE), a large and complex human enzyme, was produced via semicontinuous operation in a transgenic rice cell suspension culture. After transformation of rice callus and screening of transformants, the cultures were scaled up from culture flask to a lab scale bioreactor. The bioreactor was operated through two phases each of growth and expression. The cells were able to produce BChE during both expression phases, with a maximum yield of 1.6 mg BChE/L of culture during the second expression phase. Cells successfully regrew during a 5-day growth phase. A combination of activity assays and Western blot analysis indicated production of an active and fully assembled tetramer of BChE

R.A.P.I.D. (Root Aggregated Prioritized Information Display): A single screen display for efficient digital triaging of medical reports

AbstractObjectiveThe timely acknowledgement of critical patient clinical reports is vital for the delivery of safe patient care. With current EHR systems, critical reports reside on different screens. This leads to treatment delays and inefficient work flows. As a remedy, the R.A.P.I.D. (Root Aggregated Prioritized Information Display) system represents all data on a single screen, and its simple and intuitive “button” array structure allows triaged sign-off/sign-out of critical and non-critical reports.Materials and methodsWith 100 hematology and chemistry reports from each of two EHR systems Meditech (Westwood, MA) and Orchard Labs, Inc. (Carmel, IN), we generated files of the reports in their individual standard display formats (enhanced Meditech-EM and enhanced Orchard-EO). We also displayed the same 200 reports in the R.A.P.I.D. format. We then conducted a randomized trial to compare the time and accuracy of acknowledgement of critical and non-critical results.ResultsThe sign-off times for reviewing the results for physician and non-physician providers, respectively, in seconds (with 95% confidence intervals) were for EM 1.78 (1.40–2.26) and 1.99 (1.72–2.30), for EO 2.69 (2.12–3.42) and 2.78 (2.40–3.21), and for R.A.P.I.D. 0.83 (0.70–0.98) and 1.58 (1.43–1.76). Non-physician providers reassigned system-defined non-critical results as critical with a frequency of 15.2% for EM, 18.4% for EO, and 7.83% for R.A.P.I.D., and critical results as non-critical with a frequency of 14.7%, 5.6%, and 5.8% respectively.DiscussionThe new display system was superior to two standard EHR systems that were significantly enhanced by first collecting the reports from their usual distributed locations and then by creating for each of the two standard EHRs a single file of reports for acknowledgement.ConclusionsFrom a single screen display of all reports, the new display system enables timely acknowledgement of critical reports for patient safety and non-critical report triage for improved provider work flows

Interactions between planets and evolved stars

Searching for planetary companions to evolved stars (e.g., white dwarfs (WD) and Cataclysmic Variables (CV)) can provide insight into the interaction between planets and evolved stars as well as on the ultimate fate of planets. We have monitored decades of CVs and their progenitors including some detached WD binaries since 2006 to search for planets orbiting these systems. In the present paper, we will show some observational results of circumbinary planets in orbits around CVs and their progenitors. Some of our findings include planets with the shortest distance to the central evolved binaries and a few multiple planetary systems orbiting binary stars. Finally, by comparing the observational properties of planetary companions to single WDs and WD binaries, the interaction between planets and evolved stars and the ultimate fate of planets are discussed.Facultad de Ciencias Astronómicas y GeofísicasInstituto de Astrofísica de La Plat

Rapid assessment of sustainability in Mainland China

This paper presents an approach for rapid assessment of sustainability for Mainland China based on a multilayer index system. Efficient assessment is conducted with the basic mapping units at county and city levels. After evaluating a comprehensive sustainable development index, SDI, for each unit, five rankings of sustainability are determined, and a zonation map produced. Regional characteristics and differences are interpreted through macro-analysis of the spatial variation in SDI. A sensitivity analysis is performed by which the weights of the sub-indices are altered by +/- 20%, and SDI re-evaluated; the resulting grades remain the same, thus confirming the robustness of the technique. Moreover, the accuracy of the proposed approach is indirectly validated by comparison with assessment results from an alternative systems analysis method. It is found that major conurbations such as Beijing have relatively high levels of sustainability, whereas provinces in central and western China require investment to improve their sustainability. (C) 2009 Elsevier Ltd. All rights reserved

Examining the mechanistic relationship of APC/CCDH1 and its interphase inhibitor EMI1

Proper protein destruction by the ubiquitin (Ub)-proteasome system is vital for a faithful cell cycle. Hence, the activity of Ub ligases is tightly controlled. The Anaphase-Promoting Complex/Cyclosome (APC/C) is a 1.2MDa Ub ligase responsible for mitotic progression and G1 maintenance. At the G1/S transition, the APC/C is inhibited by EMI1 to prevent APC/C-dependent polyubiquitination of cell cycle effectors. EMI1 uses several interaction motifs to block the recruitment of APC/C substrates as well as the APC/C-associated E2s, UBE2C, and UBE2S. Paradoxically, EMI1 is also an APC/C substrate during G1. Using a comprehensive set of enzyme assays, we determined the context-dependent involvement of the EMI1 motifs in APC/C-dependent ubiquitination of EMI1 and other substrates. Furthermore, we demonstrated that an isolated C-terminal peptide fragment of EMI1 activates APC/C-dependent substrate priming by UBE2C. Together, these findings reveal the multiple roles of the EMI1 C-terminus for G1 maintenance and the G1/S transition