GTP and Ca2+ Modulate the Inositol 1,4,5-Trisphosphate-Dependent Ca2+ Release in Streptolysin O-Permeabilized Bovine Adrenal Chromaffin Cells

The inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release was studied using streptolysin O-permeabilized bovine adrenal chromaffin cells. The IP3-induced Ca2+ release was followed by Ca2+ reuptake into intracellular compartments. The IP3-induced Ca2+ release diminished after sequential applications of the same amount of IP3. Addition of 20 μM GTP fully restored the sensitivity to IP3. Guanosine 5'-O-(3-thio)triphosphate (GTPγS) could not replace GTP but prevented the action of GTP. The effects of GTP and GTPγS were reversible. Neither GTP nor GTPγS induced release of Ca2+ in the absence of IP3. The amount of Ca2+ whose release was induced by IP3 depended on the free Ca2+ concentration of the medium. At 0.3 μM free Ca2+, a half-maximal Ca2+ release was elicited with ∼0.1 μM IP3. At 1 μM free Ca2+, no Ca2+ release was observed with 0.1 μM IP3; at this Ca2+ concentration, higher concentrations of IP3 (0.25 μM) were required to evoke Ca2+ release. At 8 μM free Ca2+, even 0.25 μM IP3 failed to induce release of Ca2+ from the store. The IP3-induced Ca2+ release at constant low (0.2 μM) free Ca2+ concentrations correlated directly with the amount of stored Ca2+. Depending on the filling state of the intracellular compartment, 1 mol of IP3 induced release of between 5 and 30 mol of Ca2+

Hybrid core-multishell nanowire forests for electrical connector applications

Electrical connectors based on hybrid core-multishell nanowire forests that require low engagement forces are demonstrated. The physical binding and electrical connectivity of the nanowire electrical connectors arise from the van der Waals interactions between the conductive metallic shells of the engaged nanowire forests. Specifically, the nanofibrillar structure of the connectors causes an amplification of the contact area between the interpenetrating nanowire arrays, resulting in strong adhesion with relatively low interfacial resistance. The nanowire electrical connectors may enable the exploration of a wide range of applications involving reversible assembly of micro- and macroscale components with built-in electrical interfacing.open151

Ultrathin compound semiconductor on insulator layers for high performance nanoscale transistors

Over the past several years, the inherent scaling limitations of electron devices have fueled the exploration of high carrier mobility semiconductors as a Si replacement to further enhance the device performance. In particular, compound semiconductors heterogeneously integrated on Si substrates have been actively studied, combining the high mobility of III-V semiconductors and the well-established, low cost processing of Si technology. This integration, however, presents significant challenges. Conventionally, heteroepitaxial growth of complex multilayers on Si has been explored. Besides complexity, high defect densities and junction leakage currents present limitations in the approach. Motivated by this challenge, here we utilize an epitaxial transfer method for the integration of ultrathin layers of single-crystalline InAs on Si/SiO2 substrates. As a parallel to silicon-on-insulator (SOI) technology14,we use the abbreviation "XOI" to represent our compound semiconductor-on-insulator platform. Through experiments and simulation, the electrical properties of InAs XOI transistors are explored, elucidating the critical role of quantum confinement in the transport properties of ultrathin XOI layers. Importantly, a high quality InAs/dielectric interface is obtained by the use of a novel thermally grown interfacial InAsOx layer (~1 nm thick). The fabricated FETs exhibit an impressive peak transconductance of ~1.6 mS/{\mu}m at VDS=0.5V with ON/OFF current ratio of greater than 10,000 and a subthreshold swing of 107-150 mV/decade for a channel length of ~0.5 {\mu}m

Correlating the nanostructure and electronic properties of InAs nanowires

The electronic properties and nanostructure of InAs nanowires are correlated by creating multiple field effect transistors (FETs) on nanowires grown to have low and high defect density segments. 4.2 K carrier mobilities are ~4X larger in the nominally defect-free segments of the wire. We also find that dark field optical intensity is correlated with the mobility, suggesting a simple route for selecting wires with a low defect density. At low temperatures, FETs fabricated on high defect density segments of InAs nanowires showed transport properties consistent with single electron charging, even on devices with low resistance ohmic contacts. The charging energies obtained suggest quantum dot formation at defects in the wires. These results reinforce the importance of controlling the defect density in order to produce high quality electrical and optical devices using InAs nanowires.Comment: Related papers at http://pettagroup.princeton.ed

Protein interactions with piALU RNA indicates putative participation of retroRNA in the cell cycle, DNA repair and chromatin assembly

Recent analyses suggest that transposable element-derived transcripts are processed to yield a variety of small RNA species that play critical functional roles in gene regulation and chromatin organization as well as genome stability and maintenance. Here we report a mass spectrometry analysis of an RNA-affinity complex isolation using a piRNA homologous sequence derived from Alu retrotransposal RNA. Our data point to potential roles for piALU RNAs in DNA repair, cell cycle and chromatin regulations

Do Physicians Know When Their Diagnoses Are Correct?

This study explores the alignment between physicians' confidence in their diagnoses and the “correctness” of these diagnoses, as a function of clinical experience, and whether subjects were prone to over-or underconfidence. Design : Prospective, counterbalanced experimental design. Setting : Laboratory study conducted under controlled conditions at three academic medical centers. Participants : Seventy-two senior medical students, 72 senior medical residents, and 72 faculty internists. Intervention : We created highly detailed, 2-to 4-page synopses of 36 diagnostically challenging medical cases, each with a definitive correct diagnosis. Subjects generated a differential diagnosis for each of 9 assigned cases, and indicated their level of confidence in each diagnosis. Measurements And Main Results : A differential was considered “correct” if the clinically true diagnosis was listed in that subject's hypothesis list. To assess confidence, subjects rated the likelihood that they would, at the time they generated the differential, seek assistance in reaching a diagnosis. Subjects' confidence and correctness were “mildly” aligned (Κ=.314 for all subjects, .285 for faculty, .227 for residents, and .349 for students). Residents were overconfident in 41% of cases where their confidence and correctness were not aligned, whereas faculty were overconfident in 36% of such cases and students in 25%. Conclusions : Even experienced clinicians may be unaware of the correctness of their diagnoses at the time they make them. Medical decision support systems, and other interventions designed to reduce medical errors, cannot rely exclusively on clinicians' perceptions of their needs for such support.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74850/1/j.1525-1497.2005.30145.x.pd

Advantages of dynamic “closed loop” stable isotope flux phenotyping over static “open loop” clamps in detecting silent genetic and dietary phenotypes

In vivo insulin sensitivity can be assessed using “open loop” clamp or “closed loop” methods. Open loop clamp methods are static, and fix plasma glucose independently from plasma insulin. Closed loop methods are dynamic, and assess glucose disposal in response to a stable isotope labeled glucose tolerance test. Using PPARα−/− mice, open and closed loop assessments of insulin sensitivity/glucose disposal were compared. Indirect calorimetry done for the assessment of diurnal substrate utilization/metabolic flexibility showed that chow fed PPARα−/− mice had increased glucose utilization during the light (starved) cycle. Euglycemic clamps showed no differences in insulin stimulated glucose disposal, whether for chow or high fat diets, but did show differences in basal glucose clearance for chow fed PPARα−/− versus SV129J-wt mice. In contrast, the dynamic stable isotope labeled glucose tolerance tests reveal enhanced glucose disposal for PPARα−/− versus SV129J-wt, for chow and high fat diets. Area under the curve for plasma labeled and unlabeled glucose for PPARα−/− was ≈1.7-fold lower, P < 0.01 during the stable isotope labeled glucose tolerance test for both diets. Area under the curve for plasma insulin was 5-fold less for the chow fed SV129J-wt (P < 0.01) but showed no difference on a high fat diet (0.30 ± 0.1 for SV129J-wt vs. 0.13 ± 0.10 for PPARα−/−, P = 0.28). This study demonstrates that dynamic stable isotope labeled glucose tolerance test can assess “silent” metabolic phenotypes, not detectable by the static, “open loop”, euglycemic or hyperglycemic clamps. Both open loop and closed loop methods may describe different aspects of metabolic inflexibility and insulin sensitivity

Effect of defects on reaction of NiO surface with Pb-contained solution

In order to understand the role of defects in chemical reactions, we used two types of samples, which are molecular beam epitaxy (MBE) grown NiO(001) film on Mg(001) substrate as the defect free NiO prototype and NiO grown on Ni(110) single crystal as the one with defects. In-situ observations for oxide-liquid interfacial structure and surface morphology were performed for both samples in water and Pb-contained solution using high-resolution X-ray reflectivity and atomic force microscopy. For the MBE grown NiO, no significant changes were detected in the high-resolution X-ray reflectivity data with monotonic increase in roughness. Meanwhile, in the case of native grown NiO on Ni(110), significant changes in both the morphology and atomistic structure at the interface were observed when immersed in water and Pb-contained solution. Our results provide simple and direct experimental evidence of the role of the defects in chemical reaction of oxide surfaces with both water and Pb-contained solution.ope

The muscarinic receptor antagonist propiverine exhibits α1-adrenoceptor antagonism in human prostate and porcine trigonum

Combination therapy of male lower urinary tract symptoms with α(1)-adrenoceptor and muscarinic receptor antagonists attracts increasing interest. Propiverine is a muscarinic receptor antagonist possessing additional properties, i.e., block of L-type Ca(2+) channels. Here, we have investigated whether propiverine and its metabolites can additionally antagonize α(1)-adrenoceptors. Human prostate and porcine trigone muscle strips were used to explore inhibition of α(1)-adrenoceptor-mediated contractile responses. Chinese hamster ovary (CHO) cells expressing cloned human α(1)-adrenoceptors were used to determine direct interactions with the receptor in radioligand binding and intracellular Ca(2+) elevation assays. Propiverine concentration-dependently reversed contraction of human prostate pre-contracted with 10 μM phenylephrine (-log IC(50) [M] 4.43 ± 0.08). Similar inhibition was observed in porcine trigone (-log IC(50) 5.01 ± 0.05), and in additional experiments consisted mainly of reduced maximum phenylephrine responses. At concentrations ≥1 μM, the propiverine metabolite M-14 also relaxed phenylephrine pre-contracted trigone strips, whereas metabolites M-5 and M-6 were ineffective. In radioligand binding experiments, propiverine and M-14 exhibited similar affinity for the three α(1)-adrenoceptor subtypes with -log K (i) [M] values ranging from 4.72 to 4.94, whereas the M-5 and M-6 did not affect [(3)H]-prazosin binding. In CHO cells, propiverine inhibited α(1)-adrenoceptor-mediated Ca(2+) elevations with similar potency as radioligand binding, again mainly by reducing maximum responses. In contrast to other muscarinic receptor antagonists, propiverine exerts additional L-type Ca(2+)-channel blocking and α(1)-adrenoceptor antagonist effects. It remains to be determined clinically, how these additional properties contribute to the clinical effects of propiverine, particularly in male voiding dysfunctio

Temperature Dependence of Photochemical Degradation of MAPbBr3 Perovskite

The experimental results of X-ray diffraction (XRD), optical absorbance, scanning electron microscopy (SEM), and X-ray photoelectron spectra (XPS) of the core levels and valence bands of MAPbBr3 (MA-CH3NH3+) perovskite before and after exposure to visible light for 700 h at temperatures of 10 and 60 °C are presented. It reveals that the light soaking at 60 °C induces the decomposition of MAPbBr3 perovskite accompanied with the decay of organic cation and the release of a PbBr2 phase as a degradation product whereas the photochemical degradation completely disappears while the aging temperature is decreased to 10 °C. © 2022 by the authors.Russian Foundation for Basic Research, РФФИ: 21-52-52002; Ministry of Education and Science of the Russian Federation, Minobrnauka: AAAA-A18–118020190098-5, FEUZ 2020-0060; Ministry of Science and Technology, Taiwan, MOST: 110-2923-E-002-007-MY3; Russian Science Foundation, RSF: 19-73-30020I.S.Z. and A.I.K. thank the Ministry of Science and Higher Education of the Russian Federation (Ural Federal University Program of Development within the Priority-2030 Program) for support.This work was supported by the Russian Science Foundation (Project 19-73-30020) at IPCP RAS. The XPS measurements were supported by the Ministry of Science and Higher Education of the Russian Federation under the theme “Electron” No. AAAA-A18–118020190098-5 and Project FEUZ 2020-0060 as well as the Russian Foundation for Basic Research (Project No. 21-52-52002). The research fundings from the Ministry of Science and Technology in Taiwan (MOST 110-2923-E-002-007-MY3) are gratefully acknowledged