In situ observation of austenite coarsening induced by massive-like transformation during solidification in Fe–C alloys

MCWASP XV: International Conference on Modelling of Casting, Welding and Advanced Solidification Processes 22-23 June 2020, Jönköping, Sweden.A massive-like transformation, in which δ-ferrite massively transforms to γ-austenite in the solid state, was examined by time-resolved X-ray imaging and X-ray diffractometry on a four-dimensional–computed tomography setup. In the unidirectional solidification of a hyperperitectic steel (0.3 mass% C) at 50 μm/s, δ dendrites, fine γ grains that are produced through the massive-like transformation, and coarse γ grains grow together in the steady state. The massive-like transformation occurred commonly in Fe-based alloys with a peritectic reaction in equilibrium. Time-resolved X-ray diffraction measurements for a peritectic steel (0.18 mass% C) showed that the massive-like transformation induced strains in the γ grains. The fine γ grains coarsened and/or vanished and new γ grains formed. The induced strains were released during coarsening. The results obtained by the observations contribute to building of a physical model for γ grain coarsening

Effect of intracellular free calcium mobilization on aggregation of umbilical cord blood platelets.

&#60;P&#62;Aggregation activity of platelets in umbilical blood is lower than that in adult blood, but the reason for this is not well understood. It has recently been clarified that calcium plays a role as a second messenger of platelet aggregation, and that glycoproteins of platelet surface membrane such as glycoprotein I b and IIb/IIIa are receptors for agonists inducing aggregation. We examined the concentrations of intracellular calcium and the membrane glycoproteins of platelets in umbilical and adult blood. The increase of intracellular calcium in umbilical platelets was lower than that in adult platelets when the aggregation was induced by ADP, collagen, thrombin and epinephrine. Only calcium ionophore A23187 induced aggregation of both umbilical and adult platelets. On the other hand, there were no qualitative differences between glycoproteins I b and IIb/IIIa of these two groups. Therefore, the low aggregation activity of umbilical platelets seems to be due to low responsiveness of the intracellular calcium system, not to the disorder of functional surface membrane glycoprotein.&#60;/P&#62;</p

Prediction of Opioid-Induced Respiratory Depression on Inpatient Wards Using Continuous Capnography and Oximetry: An International Prospective, Observational Trial.

BACKGROUND: Opioid-related adverse events are a serious problem in hospitalized patients. Little is known about patients who are likely to experience opioid-induced respiratory depression events on the general care floor and may benefit from improved monitoring and early intervention. The trial objective was to derive and validate a risk prediction tool for respiratory depression in patients receiving opioids, as detected by continuous pulse oximetry and capnography monitoring. METHODS: PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) was a prospective, observational trial of blinded continuous capnography and oximetry conducted at 16 sites in the United States, Europe, and Asia. Vital signs were intermittently monitored per standard of care. A total of 1335 patients receiving parenteral opioids and continuously monitored on the general care floor were included in the analysis. A respiratory depression episode was defined as respiratory rate ≤5 breaths/min (bpm), oxygen saturation ≤85%, or end-tidal carbon dioxide ≤15 or ≥60 mm Hg for ≥3 minutes; apnea episode lasting \u3e30 seconds; or any respiratory opioid-related adverse event. A risk prediction tool was derived using a multivariable logistic regression model of 46 a priori defined risk factors with stepwise selection and was internally validated by bootstrapping. RESULTS: One or more respiratory depression episodes were detected in 614 (46%) of 1335 general care floor patients (43% male; mean age, 58 ± 14 years) continuously monitored for a median of 24 hours (interquartile range [IQR], 17-26). A multivariable respiratory depression prediction model with area under the curve of 0.740 was developed using 5 independent variables: age ≥60 (in decades), sex, opioid naivety, sleep disorders, and chronic heart failure. The PRODIGY risk prediction tool showed significant separation between patients with and without respiratory depression (P \u3c .001) and an odds ratio of 6.07 (95% confidence interval [CI], 4.44-8.30; P \u3c .001) between the high- and low-risk groups. Compared to patients without respiratory depression episodes, mean hospital length of stay was 3 days longer in patients with ≥1 respiratory depression episode (10.5 ± 10.8 vs 7.7 ± 7.8 days; P \u3c .0001) identified using continuous oximetry and capnography monitoring. CONCLUSIONS: A PRODIGY risk prediction model, derived from continuous oximetry and capnography, accurately predicts respiratory depression episodes in patients receiving opioids on the general care floor. Implementation of the PRODIGY score to determine the need for continuous monitoring may be a first step to reduce the incidence and consequences of respiratory compromise in patients receiving opioids on the general care floor

Ribosomal Synthesis of an Amphotericin‑B Inspired Macrocycle

Here we report in vitro ribosomal synthesis of a natural product-like macrocyclic peptide, inspired by the structure of amphotericin B (AmB), an amphiphilic and membrane-interacting antifungal natural product. This AmB-inspired macrocyclic peptide (AmP), one side of which is composed of hydrophobic terpene, and the other side comprises a peptidic chain, was synthesized utilizing flexizyme-assisted in vitro translation via an unusual but successful initiation with a d-cysteine derivative. The established method for the synthesis of AmPs is applicable to the generation of a diverse AmP library coupled with an in vitro display format, with the potential to lead to the discovery of artificial bioactive amphiphilic macrocycles

Exercise training increases CISD family protein expression in murine skeletal muscle and white adipose tissue

Mitochondrial function in skeletal muscle and white adipose tissue (WAT) declines with aging and the progression of type 2 diabetes and insulin resistance. Although exercise increases mitochondrial biogenesis and function in both tissues, the molecular mechanisms are not fully understood. CDGSH iron sulfur domain-containing proteins (CISDs) are a novel family of proteins that regulate mitochondrial activity and biogenesis. However, the relationship between exercise and CISD expression is unclear. We addressed this in the present study by examining changes in the expression of CISDs and mitochondrial proteins in skeletal muscle and WAT of mice subjected to chronic exercise training. Mice were randomly assigned to either the sedentary or exercise group and were housed for 4 weeks in a standard cage without or with a running wheel, respectively. CISD and mitochondrial protein levels in the plantaris and soleus muscles and epididymal WAT were evaluated by western blotting. Chronic exercise increased CISD1 and CISD2 as well as mitochondrial protein expression in plantaris muscle and WAT but not soleus muscle. Moreover, this exercise-induced adaptation was strongly correlated with mitochondrial protein expression. Thus, mitochondrial biogenesis induced by chronic exercise coincides with the expression of CISDs in specific tissues, which may be critical for the maintenance of mitochondrial integrity

Ionic Liquid-Triggered Redox Molecule Placement in Block Copolymer Nanotemplates toward an Organic Resistive Memory

The integration of functional components such as metal nanoparticles, metal salts, or ionic liquids with well-defined block copolymer (BCP) nanotemplates via noncovalent bond interactions has afforded hybrid functional materials. Here, we designed an ionic liquid (IL)-functionalized redox-active TEMPO (2,2,6,6-tetramethylpiperidine-<i>N</i>-oxy) radical (<i>guest</i>), investigated phase-selective incorporation/placement into <i>host</i> BCP nanostructured matrices, and established a rational approach to functionalize BCP templates. On-demand domain functionalization of poly­(styrene-<i>b</i>-ethylene oxide) (PS-<i>b</i>-PEO) was triggered by ion–ionophore interaction, as verified by the suppression of PEO melting transition in DSC, and the swelling behavior of the PEO spherical domain in AFM, TEM, and X-ray scattering characterizations. The obtained BCP layer containing the redox-active TEMPO and IL was utilized as an active layer in the diode-structured memory device, which exhibited on/off resistive switching (on/off ratio >10³). Systematic placement of TEMPO and IL in the BCP spherical domain allowed for tuning of the switching characteristics and revealed that the formation of a discontinuous redox-active domain was critical for rewritable resistive switching

Exercise-induced mitochondrial biogenesis coincides with the expression of mitochondrial translation factors in murine skeletal muscle

The process of mitochondrial translation, in which mitochondrial (mt)DNA‐encoded genes are translated into proteins, is crucial for mitochondrial function and biogenesis. In each phase, a series of mitochondrial translation factors is required for the synthesis of mtDNA‐encoded mitochondrial proteins. Two mitochondrial initiation factors (mtIF2 and mtIF3), three mitochondrial elongation factors (mtEFTu, mtEFTs, and mtEFG1), one mitochondrial release factor (mtRF1L), and two mitochondrial recycling factors (mtRRF1 and mtRRF2) are mitochondrial translation factors that coordinate each translational phase. Exercise increases both nuclear DNA‐ and mtDNA‐encoded mitochondrial proteins, resulting in mitochondrial biogenesis in skeletal muscles. Therefore, mitochondrial translation factors are likely regulated by exercise; however, it is unclear whether exercise affects mitochondrial translation factors in the skeletal muscles. We investigated whether exercise training comprehensively increases this series of mitochondrial translation factors, as well as mtDNA‐encoded proteins, in the skeletal muscle. Mice were randomly assigned to either the sedentary or exercise group and housed in standard cages with or without a running wheel for 1 and 8 weeks. The expression levels of mitochondrial translation factors in the plantaris and soleus muscles were then measured. Exercise training concomitantly upregulated mitochondrial translation factors and mitochondrial proteins in the plantaris muscle. However, in the soleus muscle, these comprehensive upregulations were not detected. These results indicate that exercise‐induced mitochondrial biogenesis coincides with the upregulation of mitochondrial translation factors