Publications

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

In the version of the article initially published, the x axes in Figs. 2b,d and 5a,b originally read “T<sup>-1</sup> (K<sup>-1</sup>)” and have now been amended to “1000 T<sup>-1</sup> (K<sup>-1</sup>)” in the HTML and PDF versions of the article.

Summary Reduced cell wall recalcitrance and increased C6 monosaccharide content are desirable traits for future biofuel crops, as long as these biomass modifications do not significantly alter normal growth and development. Mixed‐linkage glucan ( MLG ), a cell wall polysaccharide only present in grasses and related species among flowering plants, is comprised of glucose monomers linked by both β‐1,3 and β‐1,4 bonds. Previous data have shown that constitutive production of MLG in barley ( Hordeum vulgare ) severely compromises growth and development. Here, we used spatio‐temporal strategies to engineer Arabidopsis thaliana plants to accumulate significant amounts of MLG in the cell wall by expressing the rice CslF6 MLG synthase using secondary cell wall and senescence‐associated promoters. Results using secondary wall promoters were suboptimal. When the rice MLG synthase was expressed under the control of a senescence‐associated promoter, we obtained up to four times more glucose in the matrix cell wall fraction and up to a 42% increase in saccharification compared to control lines. Importantly, these plants grew and developed normally. The induction of MLG deposition at senescence correlated with an increase of gluconic acid in cell wall extracts of transgenic plants in contrast to the other approaches presented in this study. MLG produced in Arabidopsis has an altered structure compared to the grass glucan, which likely affects its solubility, while its molecular size is unaffected. The induction of cell wall polysaccharide biosynthesis in senescing tissues offers a novel engineering alternative to enhance cell wall properties of lignocellulosic biofuel crops.

Epilepsy constitutes a clinically-manifest excitability disorder that is characterized by aberrant electrophysiological activity in the electroencephalogram (EEG). The correct identification of the seizure onset zone relies on the visual detection of pathological waveforms and the assessment of their morphology, rhythmicity, and density. Recent advances in quantitative EEG analyses indicated that aperiodic EEG background activity might provide complementary information to traditional qualitative methods. Importantly, aperiodic activity, and specifically the slope of the 1/ƒ χ decay function of the power spectrum, might constitute a biomarker of the underlying population excitability dynamics. Hence, in the context of epileptic activity, an altered spectral slope is often considered as a signature of pathological excitability. To date, it remained unclear if this straightforward interpretation also applies to states of manifest seizure activity. To address this question, we recorded intracranial electroencephalography (iEEG) during focal seizures from patients diagnosed with pharmacoresistant epilepsy (18 patients, 11 females). The results demonstrate that the spectral slope successfully delineates seizure activity. However, the spectral slope was sensitive to the presence and waveform shape of distinct epileptic components. By combining iEEG recordings with simulations, we demonstrate that epileptic spiking activity and associated slow-wave components differentially impact spectral slope estimates. These results offer a more parsimonious explanation for the biophysical origins of aperiodic activity as compared to the concept of an underlying balance between excitation and inhibition. Significance Statement It is under debate whether the non-oscillatory EEG background (aperiodic) component of electrophysiological brain activity provides diagnostic insights into clinical disorders such as epilepsy. Seizure-related changes in aperiodic activity have mostly been ascribed to pathological excitability. Yet, epileptic waveform shapes could potentially modulate spectral estimates of aperiodic activity. Heidiri et al. demonstrate that aperiodic activity tracks ictal activity, wherein the morphology and density of epileptic activity systematically distort spectral estimates and associated aperiodic estimates. These findings show that aperiodic activity is directly modulated by the presence of waveform shapes, and may not necessarily reflect pathologic aberrations in the underlying population excitability.

We report a spectroscopic search for hypervelocity white dwarfs (WDs) that are runaways from Type Ia supernovae (SNe Ia) and related thermonuclear explosions. Candidates are selected from Gaia data with high tangential velocities and blue colors. We find six new runaways, including four stars with radial velocities (RVs) $>1000\,\rm km\,s^{-1}$ and total space velocities $\gtrsim 1300\,\rm km\,s^{-1}$. These are most likely the surviving donors from double-degenerate binaries in which the other WD exploded. The other two objects have lower minimum velocities, $\gtrsim 600\,\rm km\,s^{-1}$, and may have formed through a different mechanism, such as pure deflagration of a WD in a Type Iax supernova. The four fastest stars are hotter and smaller than the previously known "D$^6$ stars," with effective temperatures ranging from $\sim$20,000 to $\sim$130,000 K and radii of $\sim 0.02-0.10\,R_{\odot}$. Three of these have carbon-dominated atmospheres, and one has a helium-dominated atmosphere. Two stars have RVs of $-1694$ and $-2285\rm \,km\,s^{-1}$ -- the fastest systemic stellar RVs ever measured. Their inferred birth velocities, $\sim 2200-2500\,\rm km\,s^{-1}$, imply that both WDs in the progenitor binary had masses $>1.0\,M_{\odot}$. The high observed velocities suggest that a dominant fraction of the observed hypervelocity WD population comes from double-degenerate binaries whose total mass significantly exceeds the Chandrasekhar limit. However, the two nearest and faintest D$^6$ stars have the lowest velocities and masses, suggesting that observational selection effects favor rarer, higher-mass stars. A significant population of fainter low-mass runaways may still await discovery. We infer a birth rate of D$^6$ stars that is consistent with the SN Ia rate. The birth rate is poorly constrained, however, because the luminosities and lifetimes of $\rm D^6$ stars are uncertain.

Abstract Background: Despite evidence that low muscle increases the risk of chemotoxicity, most chemotherapies are dosed on body surface area without considering body composition. Among 178 patients with colon cancer, we assessed muscle and adipose tissue with multiple techniques and examined their associations with relative dose intensity (RDI) and adverse events. Methods: We estimated (i) cross-sectional skeletal muscle area (SMA) and total adipose tissue (TAT) area at L3 from computed tomography (CT); (ii) appendicular lean mass (ALM) and total body fat (TBF) mass from dual-energy X-ray absorptiometry (DXA); and (iii) total body skeletal muscle mass using D3-creatine (D3Cr) dilution. We standardized each measurement by its sex-specific standard deviation (SD). The primary outcome was reduced RDI (RDI <85%). The secondary outcome was the number of moderate and severe adverse events during each cycle of chemotherapy. We estimated the associations of muscle and adipose tissue measurements (per SD increase) with reduced RDI using logistic regression and adverse events using generalized estimating equations for repeated measures. Results: Higher CT SMA and DXA ALM were significantly associated with a lower risk of reduced RDI [odds ratios: 0.56 (0.38–0.81) for CT SMA; 0.56 (0.37–0.84) for DXA ALM]. No measurements of muscle or adipose tissue were associated with adverse events. Conclusions: More muscle was associated with improved chemotherapy completion among patients with colon cancer, whereas muscle and adipose tissue were not associated with adverse events. Impact: Considering body composition may help personalize dosing for colon cancer chemotherapy by identifying patients at risk for poor chemotherapy outcomes.

Surface-immobilized poly(N-isopropyl acrylamide) (pNIPAM) is currently used for a wide variety of biosensor and biomaterial applications. A thorough characterization of the surface properties of pNIPAM thin films will benefit those applications. In this work, we present analysis of a plasma-polymerized NIPAM (ppNIPAM) coating by multiple surface analytical techniques, including time-of-flight secondary-ion mass spectrometry (ToF-SIMS), contact angle measurement, atomic force microscopy (AFM), and sum frequency generation (SFG) vibrational spectroscopy. ToF-SIMS data show that the plasma-deposited NIPAM polymer on the substrate is cross-linked with a good retention of the monomer integrity. Contact angle results confirm the thermoresponsive nature of the film as observed by a change of surface wettability as a function of temperature. Topographic and force-distance curve measurements by AFM further demonstrate that the grafted film shrinks or swells depending on the temperature of the aqueous environment. A clear transition of the elastic modulus is observed at 31-32 degrees C. The change of the surface wettability and mechanical properties vs temperature are attributed to different conformations taken by the polymer, which is reflected on the outmost surface as distinct side chain groups orienting outward at different temperatures as measured by SFG. The results suggest that a ppNIPAM thin film on a substrate experiences similar mechanical and chemical changes to pNIPAM bulk polymers in solution. The SFG result provides evidence supporting the current theory of the lower critical solution temperature (LCST) behavior of pNIPAM.

<p>Gene expression levels of Fatp5, and Fasn were measured using qPCR in AAV-shSCR and AAV-shFatp5 ICC tumors.</p>