Glucose regulated protein 78 (GRP78) functions as a sensor of endoplasmic reticulum (ER) stress. The aim of this study was to test the hypothesis that molecules that bind to GRP78 induce the unfolded ...protein response (UPR) and enhance cell death in combination with ER stress inducers.
Differential scanning calorimetry (DSC), measurement of cell death by flow cytometry and the induction of ER stress markers using western blotting.
Epigallocatechin gallate (EGCG), a flavonoid component of Green Tea Camellia sinensis, and honokiol (HNK), a Magnolia grandiflora derivative, bind to unfolded conformations of the GRP78 ATPase domain. Epigallocatechin gallate and HNK induced death in six neuroectodermal tumour cell lines tested. Levels of death to HNK were twice that for EGCG; half-maximal effective doses were similar but EGCG sensitivity varied more widely between cell types. Honokiol induced ER stress and UPR as predicted from its ability to interact with GRP78, but EGCG was less effective. With respect to cell death, HNK had synergistic effects on melanoma and glioblastoma cells with the ER stress inducers fenretinide or bortezomib, but only additive (fenretinide) or inhibitory (bortezomib) effects on neuroblastoma cells.
Honokiol induces apoptosis due to ER stress from an interaction with GRP78. The data are consistent with DSC results that suggest that HNK binds to GRP78 more effectively than EGCG. Therefore, HNK may warrant development as an antitumour drug.
Diagnostic point-of-care ultrasound (PoCUS) has emerged as a powerful tool to help anesthesiologists guide patient care in both the perioperative setting and the subspecialty arenas. Although ...anesthesiologists can turn to guideline statements pertaining to other aspects of ultrasound use, to date there remains little in the way of published guidance regarding diagnostic PoCUS. To this end, in 2018, the American Society of Anesthesiologists chartered an ad hoc committee consisting of 23 American Society of Anesthesiologists members to provide recommendations on this topic. The ad hoc committee convened and developed a committee work product. This work product was updated in 2021 by an expert panel of the ad hoc committee to produce the document presented herein. The document, which represents the consensus opinion of a group of practicing anesthesiologists with established expertise in diagnostic ultrasound, addresses the following issues: (1) affirms the practice of diagnostic PoCUS by adequately trained anesthesiologists, (2) identifies the scope of practice of diagnostic PoCUS relevant to anesthesiologists, (3) suggests the minimum level of training needed to achieve competence, (4) provides recommendations for how diagnostic PoCUS can be used safely and ethically, and (5) provides broad guidance about diagnostic ultrasound billing.
A manufacturing and single-cell fuel cell performance study of stamped, laser welded, and gas nitrided ferritic stainless steel foils in an advanced automotive bipolar plate assembly design was ...performed. Two developmental foil compositions were studied: Fe–20Cr–4V and Fe–23Cr–4V wt.%. Foils 0.1mm thick were stamped and then laser welded together to create single bipolar plate assemblies with cooling channels. The plates were then surface treated by pre-oxidation and nitridation in N2–4H2 based gas mixtures using either a conventional furnace or a short-cycle quartz lamp infrared heating system. Single-cell fuel cell testing was performed at 80°C for 500h at 0.3A/cm2 using 100% humidification and a 100%/40% humidification cycle that stresses the membrane and enhances release of the fluoride ion and promotes a more corrosive environment for the bipolar plates. Periodic high frequency resistance potential-current scans during the 500h fuel cell test and post-test analysis of the membrane indicated no resistance increase of the plates and only trace levels of metal ion contamination.
► FeCrV stainless steels were manufacturable in an automotive bipolar plate design. ► Nitriding in ≤15min at 950–1000°C with a quartz lamp infrared furnace. ► Nitrided plates exhibited stable HFR and low metal ion contamination.
Thermal (gas) nitridation of stainless steel alloys can yield low interfacial contact resistance (ICR), electrically conductive and corrosion-resistant nitride containing surface layers (Cr
2N, CrN, ...TiN, V
2N, VN, etc.) of interest for fuel cells, batteries, and sensors. This paper presents results of scale-up studies to determine the feasibility of extending the nitridation approach to thin 0.1
mm stainless steel alloy foils for proton exchange membrane fuel cell (PEMFC) bipolar plates. Developmental Fe–20Cr–4V alloy and type 2205 stainless steel foils were treated by pre-oxidation and nitridation to form low-ICR, corrosion-resistant surfaces. As-treated Fe–20Cr–4V foil exhibited target (low) ICR values, whereas 2205 foil suffered from run-to-run variation in ICR values, ranging up to 2× the target value. Pre-oxidized and nitrided surface structure examination revealed surface-through-layer-thickness V-nitride particles for the treated Fe–20Cr–4V, but near continuous chromia for treated 2205 stainless steel, which was linked to the variation in ICR values. Promising corrosion resistance was observed under simulated aggressive PEMFC anode- and cathode-side bipolar plate conditions for both materials, although ICR values were observed to increase. The implications of these findings for stamped bipolar plate foils are discussed.
We present the detection of three exoplanets orbiting the early M dwarf TOI-663 (TIC 54962195; V = 13.7 mag, J = 10.4 mag, R ★ = 0.512 ± 0.015 R ⊙ , M ★ = 0.514 ± 0.012 M ⊙ , d = 64 pc). TOI-663 b, ...c, and d, with respective radii of 2.27 ± 0.10 R ⊕ , 2.26 ± 0.10 R ⊕ , and 1.92 ± 0.13 R ⊕ and masses of 4.45 ± 0.65 M ⊕ , 3.65 ± 0.97 M ⊕ , and <5.2 M ⊕ at 99%, are located just above the radius valley that separates rocky and volatile-rich exoplanets. The planet candidates are identified in two TESS sectors and are validated with ground-based photometric follow-up, precise radial-velocity measurements, and high-resolution imaging. We used the software package juliet to jointly model the photometric and radial-velocity datasets, with Gaussian processes applied to correct for systematics. The three planets discovered in the TOI-663 system are low-mass mini-Neptunes with radii significantly larger than those of rocky analogs, implying that volatiles, such as water, must predominate. In addition to this internal structure analysis, we also performed a dynamical analysis that confirmed the stability of the system. The three exoplanets in the TOI-663 system, similarly to other sub-Neptunes orbiting M dwarfs, have been found to have lower densities than planets of similar sizes orbiting stars of different spectral types.
p53 exerts its cell cycle regulatory effects through its ability to function as a sequence-specific DNA binding transcription factor. CREB-binding protein (CBP)/p300, through its interaction with the ...N terminus of p53, acts as a coactivator for p53 and increases the sequence-specific DNA-binding activity of p53 by acetylating its C terminus. The same N-terminal domain of p53 has recently been shown to be phosphorylated at Ser15 in response to γ-irradiation. Remarkably, we now demonstrate that phosphorylation of p53 at Ser15 increases its ability to recruit CBP/p300. The increase in CBP/p300 binding was followed by an increase in the overall level of acetylation of the C terminus of p53. These results provide a mechanism for the activation of p53-regulated genes following DNA damage, through a signaling pathway linking p53 N-terminal kinase and C-terminal acetyltransferase activities.
We perform a statistical standard siren analysis of GW170817. Our analysis does not utilize knowledge of NGC 4993 as the unique host galaxy of the optical counterpart to GW170817. Instead, we ...consider each galaxy within the GW170817 localization region as a potential host; combining the redshifts from all of the galaxies with the distance estimate from GW170817 provides an estimate of the Hubble constant, H0. Considering all galaxies brighter than as equally likely to host a binary neutron star merger, we find km s−1 Mpc−1 (maximum a posteriori and 68.3% highest density posterior interval; assuming a flat H0 prior in the range km s−1 Mpc−1). We explore the dependence of our results on the thresholds by which galaxies are included in our sample, and we show that weighting the host galaxies by stellar mass or star formation rate provides entirely consistent results with potentially tighter constraints. By applying the method to simulated gravitational-wave events and a realistic galaxy catalog we show that, because of the small localization volume, this statistical standard siren analysis of GW170817 provides an unusually informative (top 10%) constraint. Under optimistic assumptions for galaxy completeness and redshift uncertainty, we find that dark binary neutron star measurements of H0 will converge as , where N is the number of sources. While these statistical estimates are inferior to the value from the counterpart standard siren measurement utilizing NGC 4993 as the unique host, km s−1 Mpc−1 (determined from the same publicly available data), our analysis is a proof-of-principle demonstration of the statistical approach first proposed by Bernard Schutz over 30 yr ago.
Tests of General Relativity with GW150914 Aguiar, O D; Arceneaux, C C; Arnaud, N ...
Physical review letters,
2016-Jun-03, Volume:
116, Issue:
22
Journal Article, Web Resource
Peer reviewed
Open access
The LIGO detection of GW150914 provides an unprecedented opportunity to study the two-body motion of a compact-object binary in the large-velocity, highly nonlinear regime, and to witness the final ...merger of the binary and the excitation of uniquely relativistic modes of the gravitational field. We carry out several investigations to determine whether GW150914 is consistent with a binary black-hole merger in general relativity. We find that the final remnant's mass and spin, as determined from the low-frequency (inspiral) and high-frequency (postinspiral) phases of the signal, are mutually consistent with the binary black-hole solution in general relativity. Furthermore, the data following the peak of GW150914 are consistent with the least-damped quasinormal mode inferred from the mass and spin of the remnant black hole. By using waveform models that allow for parametrized general-relativity violations during the inspiral and merger phases, we perform quantitative tests on the gravitational-wave phase in the dynamical regime and we determine the first empirical bounds on several high-order post-Newtonian coefficients. We constrain the graviton Compton wavelength, assuming that gravitons are dispersed in vacuum in the same way as particles with mass, obtaining a 90%-confidence lower bound of 10^{13} km. In conclusion, within our statistical uncertainties, we find no evidence for violations of general relativity in the genuinely strong-field regime of gravity.
Gas nitridation has shown excellent promise to form dense, electrically conductive and corrosion-resistant Cr-nitride surface layers on Ni–Cr base alloys for use as proton exchange membrane fuel cell ...(PEMFC) bipolar plates. Due to the high cost of nickel, Fe-base bipolar plate alloys are needed to meet the cost targets for many PEMFC applications. Unfortunately, nitridation of Fe-base stainless steel alloys typically leads to internal Cr-nitride precipitation rather than the desired protective surface nitride layer formation, due to the high permeability of nitrogen in these alloys. This paper reports the finding that it is possible to form a continuous, protective Cr-nitride (CrN and Cr
2N) surface layer through nitridation of Fe-base stainless steel alloys. The key to form a protective Cr-nitride surface layer was found to be the initial formation of oxide during nitridation, which prevented the internal nitridation typically observed for these alloys, and resulted in external Cr-nitride layer formation. The addition of V to the alloy, which resulted in the initial formation of V
2O
3–Cr
2O
3, was found to enhance this effect, by making the initially formed oxide more amenable to subsequent nitridation. The Cr-nitride surface layer formed on model V-modified Fe–27Cr alloys exhibited excellent corrosion resistance and low interfacial contact resistance under simulated PEMFC bipolar plate conditions.
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