CsV3 Sb5 is a newly discovered Z2 topological kagome metal showing the coexistence of a charge-density-wave (CDW)-like order at T* = 94 K and superconductivity (SC) at Tc = 2.5 K at ambient pressure. ...Here, we study the interplay between CDW and SC in CsV3 Sb5 via measurements of resistivity, dc and ac magnetic susceptibility under various pressures up to 6.6 GPa. We find that the CDW transition decreases with pressure and experience a subtle modification at Pc1 ≈ 0.6 – 0.9 GPa before it vanishes completely at Pc2 ≈ 2 GPa . Correspondingly, Tc(P) displays an unusual M -shaped double dome with two maxima around Pc1 and Pc2 , respectively, leading to a tripled enhancement of Tc to about 8 K at 2 GPa. The obtained temperature-pressure phase diagram resembles those of unconventional superconductors, illustrating an intimated competition between CDW-like order and SC. The competition is found to be particularly strong for the intermediate pressure range Pc1 ≤ P ≤ Pc2 as evidenced by the broad superconducting transition and reduced superconducting volume fraction. The modification of CDW order around Pc1 has been discussed based on the band structure calculations. This work not only demonstrates the potential to raise Tc of the V-based kagome superconductors, but also offers more insights into the rich physics related to the electron correlations in this novel family of topological kagome metals.
Based on new insights from crystallography, this study aims to establish the relationship between prior austenite grain size and mechanical properties and enhance our understanding of Hall-Petch ...relationship. The refinement of prior austenite grains was achieved by decreasing the austenitizing temperature (from 920 ℃ to 880 ℃) and quenching. In addition, samples subjected to 880 ℃ heat treatment and quenching produced a significantly higher percentage of martensite. Electron backscattered diffraction (EBSD) used to characterize the crystallographic characteristics indicated that the steel subjected to 920 ℃ heat treatment and quenched had larger prior austenite grains, belonging to the transformation of Bain group. After 880 ℃ heat treatment and quenching, the prior austenite grains were smaller and more uniform, which belonged to the transformation dominated by CP (close-packed plane) group. The transformation from Bain group to CP group was related to transformation driving force, and resulted in increase in the density of high angle grain boundaries (DHAGBs). Using thermal expansion approach to measure the initial martensite transformation temperature (Ms temperature), the samples heat treated and quenched at 920 ℃ and 880 ℃ showed Ms temperature of 400 ℃ and 427 ℃, respectively, implying that the phase transformation driving force was increased by refining the prior austenite grain. Charpy impact energy test at −40 ℃ suggested that after 880 ℃ heat treatment and quenching, the Charpy energy increased from 46 J to 92 J, consistent with the results of EBSD.
The aim was to compare viscoelastic properties of Achilles tendons between legs in elite athletes with unilateral tendinosis, and to investigate relationships between the properties and explosive ...performance and clinical severity. Seventeen male athletes (mean ± standard deviation age, 27.3 ± 2.0 years) who had unilateral, chronic middle‐portion tendinopathy of the Achilles tendon were assessed by the Victorian Institute of Sport Assessment questionnaire, measurements of tendon viscoelastic properties, voluntary electromechanical delay (EMD), normalized rate of force development (RFD), and one‐leg hopping distance. Compared with the non‐injured leg, the tendinopathic leg showed reduced tendon stiffness (−19.2%. P < 0.001), greater mechanical hysteresis (+21.2%, P = 0.004), lower elastic energy storage and release (−14.2%, P = 0.002 and −19.1%, P < 0.001), lower normalized RFD at one‐fourth (−16.3%, P = 0.02), 2/4 (−17.3%, P = 0.006), and three‐fourths maximal voluntary contraction (−13.7%, P = 0.02), longer soleus and medial gastrocnemius voluntary EMD (+26.9%, P = 0.009 and +24.0%, P = 0.004), and shorter hopping distances (−34.1%, P < 0.001). Tendon stiffness was correlated with normalized RFD, voluntary EMD in the medial gastrocnemius, and hopping distances (r ranged from −0.35 to 0.64, P < 0.05). Hysteresis was correlated to the soleus voluntary EMD and hopping distances (r = 0.42 and −0.39, P < 0.05). We concluded that altered tendon viscoelastic properties in Achilles tendinosis affect explosive performance in athletes.
Purpose
In LOTUS (NCT02162719), adding the oral AKT inhibitor ipatasertib to first-line paclitaxel for locally advanced/metastatic triple-negative breast cancer (aTNBC) improved progression-free ...survival (PFS; primary endpoint), with an enhanced effect in patients with
PIK3CA/AKT1/PTEN
-altered tumors (FoundationOne next-generation sequencing NGS assay). We report final overall survival (OS) results.
Methods
Eligible patients had measurable previously untreated aTNBC. Patients were stratified by prior (neo)adjuvant therapy, chemotherapy-free interval, and tumor immunohistochemistry PTEN status, and were randomized 1:1 to paclitaxel 80 mg/m
2
(days 1, 8, 15) plus ipatasertib 400 mg or placebo (days 1–21) every 28 days until disease progression or unacceptable toxicity. OS (intent-to-treat ITT, immunohistochemistry PTEN-low, and PI3K/AKT pathway-activated NGS
PIK3CA/AKT1/PTEN
-altered populations) was a secondary endpoint.
Results
Median follow-up was 19.0 versus 16.0 months in the ipatasertib–paclitaxel versus placebo–paclitaxel arms, respectively. In the ITT population (
n
= 124), median OS was numerically longer with ipatasertib–paclitaxel than placebo–paclitaxel (hazard ratio 0.80, 95% CI 0.50–1.28; median 25.8 vs 16.9 months, respectively; 1-year OS 83% vs 68%). Likewise, median OS favored ipatasertib–paclitaxel in the PTEN-low (
n
= 48; 23.1 vs 15.8 months; hazard ratio 0.83) and
PIK3CA/AKT1/PTEN
-altered (
n
= 42; 25.8 vs 22.1 months; hazard ratio 1.13) subgroups. The ipatasertib–paclitaxel safety profile was unchanged.
Conclusions
Final OS results show a numerical trend favoring ipatasertib–paclitaxel and median OS exceeding 2 years with ipatasertib–paclitaxel. Overall, results are consistent with the reported PFS benefit; interpretation within biomarker-defined subgroups is complicated by small sample sizes and TNBC heterogeneity.
Lung cancer is one of the most common deadly diseases worldwide, most of which is non-small cell lung cancer (NSCLC). The epidermal growth factor receptor (EGFR) mutant NSCLCs frequently respond to ...the EGFR tyrosine kinase inhibitors (EGFR-TKIs) treatment, such as Gefitinib and Erlotinib, but the development of acquired resistance limits the utility. Multiple resistance mechanisms have been explored, e.g., the activation of alternative tyrosine kinase receptors (TKRs) sharing similar downstream pathways to EGFR. MicroRNAs (miRNAs) are short, endogenous and non-coding RNA molecules, regulating the target gene expression. In this study, we explored the potential of miR-30a-5p in targeting the EGFR and insulin-like growth factor receptor-1 (IGF-1R) signaling pathways to overcome the drug resistance. IGF-1R is one of the tyrosine kinase receptors that share the same EGFR downstream molecules, including phosphatidylinositol 3 kinase (PI3K) and protein kinase B (AKT). In this work, an
study was designed using EGFR inhibitor (Gefitinib), IGF-1R inhibitor (NVP-AEW541), and miRNA mimics in two Gefitinib-resistant NSCLC cell lines, H460 and H1975. We found that the combination of EGFR and IGF-1R inhibitors significantly decreased the phosphorylated AKT (p-AKT) expression levels compared to the control group in these two cell lines. Knockdown of phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2) had the same effect with the dual inhibition of EGFR and IGF-1R to reduce the expression of p-AKT in the signaling pathway. Overexpression of miR-30a-5p significantly reduced the expression of the PI3K regulatory subunit (PIK3R2) to further induce cell apoptosis, and inhibit cell invasion and migration properties. Hence, miR-30a-5p may play vital roles in overcoming the acquired resistance to EGFR-TKIs, and provide useful information for establishing novel cancer treatment.
The metabolic syndrome may cause disease progression in patients with chronic hepatitis B (CHB). However, the interactions between hepatitis B virus (HBV) infection and metabolic factors remain ...unknown. We investigated the association of HBV infection with metabolic profiles in HBV‐infected and noninfected subjects. In addition, the impacts of serum HBV DNA level on metabolic profiles were studied. Initially, a case–control analysis of patients with and without chronic HBV infection was performed. The HBV group consisted of 322 patients with chronic HBV infection, and the control group consisted of 870 matched subjects without HBV infection. Fasting blood glucose, lipid profiles and adiponectin levels were compared. The results were then confirmed in a second retrospective cohort study in 122 CHB patients with serum HBV DNA levels and HOMA‐IR index values. In the case–control analysis, the HBV group had significantly higher serum adiponectin, but lower triglyceride (TG) and high‐density lipoprotein cholesterol (HDL) levels than the control group. These relationships already existed in subjects younger than 45 years of age and were modified by serum alanine aminotransferase (ALT) levels. In the retrospective cohort, serum HBV DNA levels were negatively proportional to TG levels, but not to other metabolic parameters. Moreover, this relationship was significant only in subjects with higher ALT levels. Compared with healthy adults, patients with chronic HBV infection have significantly higher serum adiponectin, but lower TG and HDL levels. These relationships are modified by ALT levels and already exist in middle‐age patients with chronic HBV infection, implying HBV may interact with host metabolism.
A detailed three-dimensional thermal model has been developed to examine the thermal behaviour of a lithium-ion battery. This model precisely considers the layered-structure of the cell stacks, the ...case of a battery pack, and the gap between both elements to achieve a comprehensive analysis. Both location-dependent convection and radiation are adopted at boundaries to reflect different heat dissipation performances on all surfaces. Furthermore, a simplified thermal model is proposed according to the examination of various simplification strategies and validation from the detailed thermal model. Based on the examination, the calculation speed of the simplified model is comparable with that of a one-dimensional model with a maximum error less than 0.54
K. These models successfully describe asymmetric temperature distribution inside a battery, and they predict an anomaly of temperature distribution on the surface if a metal case is used. Based on the simulation results from the detailed thermal model, radiation could contribute 43–63% at most to the overall heat dissipation under natural convection. Forced convection is effective in depressing the maximum temperature, and the temperature uniformity does not necessarily decrease infinitely when the extent of forced convection is enhanced. The metal battery case serves as a heat spreader, and the contact layer provides extra thermal resistance and heat capacity for the system. These factors are important and should be considered seriously in the design of battery systems.
The present study contains a critical review of work on the formation of precipitates and intermetallic phases in dilute precipitation hardening Al-Cu-Mg based alloys with and without Li additions. ...Although many suggestions for the existence of pre-precipitates in Al-Cu-Mg alloys with a Cu/Mg atomic ratio close to 1 have been made, a critical review reveals that evidence exists for only two truly distinct ones. The precipitation sequence is best represented as: supersaturated solid solution→co-clusters→GPB2/S"→S where clusters are predominantly Cu-Mg co-clusters (also termed GPB or GPB I zones), GPB2/S" is an orthorhombic phase that is coherent with the matrix (probable composition Al
10
Cu
3
Mg
3
) for which both the term GPB2 and S" have been used, and S phase is the equilibrium Al
2
CuMg phase. GPB2/S" can co-exist with S phase before the completion of the formation of S phase. It is further mostly accepted that the crystal structure of S' (Al
2
CuMg) is identical to the equilibrium S phase (Al
2
CuMg). The Perlitz and Westgren model for S phase is viewed to be the most accepted structure. 3DAP analysis showed that Cu-Mg clusters form within a short time of natural and artificial aging. Cu-Mg clusters and S phase contribute to the first and second stage hardening during aging. In Al-Cu alloys, the θ phase (Al
2
Cu) has I4/mcm structure with a=0.607 nm and c=0.487 nm, and θ' phase has a tetragonal structure and a=0.404 nm, c=0.58 nm, the space group is I4m2. Gerold's model for θ" (or GPII) appears to be favourable in terms of free energy, and is consistent with most experimental data. The transformation from GPI to GPII (or θ") seems continuous, and as Cu atoms will not tend to cluster together or cluster with vacancies, the precipitation sequence can thus be captured as: supersaturated solid solution→θ" (Al
3
Cu)→θ' (Al
2
Cu)→θ(Al
2
Cu). The Ω phase (Al
2
Cu) has been variously proposed as monoclinic, orthorhombic, hexagonal and tetragonal distorted θphase structures. It has been shown that Ω phase forms initially on {111}
Al
with c=0.935 nm and on further aging, the c lattice parameter changes continuously to 0.848 nm, to become identical to the orthorhombic structure proposed by Knowles and Stobbs (a=0.496 nm, b=0.858 nm and c=0.848 nm). Other models are either wrong (for example, monoclinic and hexagonal) or refer to a transition phase (for example, the Garg and Howe model with c=0.858 in a converted orthorhombic structure). For Al-Li-Cu-Mg alloys, the L1
2
ordered metastable δ' (Al
3
Li) phase has been observed by many researchers. The Huang and Ardell model for T
1
phase (space group P6/mmm, a=0.496 nm and c=0.935 nm), appears more likely than other proposed structures. Other proposed structures are perhaps due to the T
1
phase forming by the dissociation of ½ dislocations into ⅙ Shockley partials bounding a region of intrinsic stacking fault, in which copper and lithium enrichment of the fault produces a thin layer of the T
1
phase.
Objectives
To evaluate the negative effect of physical restraint use on the hospital outcomes of older patients.
Design
A retrospective cohort study.
Setting
Internal medicine wards of a tertiary ...medical center in Taiwan.
Participants
Subjects aged 65 years and over who were admitted during April to Dec 2017 were recruited for study.
Measurements
Demographic data, geriatric assessments (polypharmacy, visual impairment, hearing impairment, activities of daily living before and after admission, risk of pressure sores, change in consciousness level, mood condition, history of falls in the previous year, risk of malnutrition and pain) and hospital conditions (admission route, department of admission, length of hospital stay and mortality) were collected for analysis.
Results
Overall, 4,352 participants (mean age 78.7±8.7 years, 60.2% = male) were enrolled and 8.3% had physical restraint. Results of multivariate logistic regression showed that subjects with physical restraints were at greater risk of functional decline (adjusted odds ratio 2.136, 95% confidence interval 1.322–3.451, p=0.002), longer hospital stays (adjusted odds ratio 5.360, 95% confidence interval 3.627–7.923, p<0.001) and mortality (adjusted odds ratio 4.472, 95% confidence interval 2.794–7.160, p<0.001) after adjustment for covariates.
Conclusion
The use of physical restraints during hospitalization increased the risk of adverse hospital outcomes, such as functional decline, longer length of hospital stay and mortality.
The retina is a specialized neural tissue that senses light and initiates image processing. Although the functional organization of specific retina cells has been well studied, the molecular profile ...of many cell types remains unclear in humans. To comprehensively profile the human retina, we performed single‐cell RNA sequencing on 20,009 cells from three donors and compiled a reference transcriptome atlas. Using unsupervised clustering analysis, we identified 18 transcriptionally distinct cell populations representing all known neural retinal cells: rod photoreceptors, cone photoreceptors, Müller glia, bipolar cells, amacrine cells, retinal ganglion cells, horizontal cells, astrocytes, and microglia. Our data captured molecular profiles for healthy and putative early degenerating rod photoreceptors, and revealed the loss of MALAT1 expression with longer post‐mortem time, which potentially suggested a novel role of MALAT1 in rod photoreceptor degeneration. We have demonstrated the use of this retina transcriptome atlas to benchmark pluripotent stem cell‐derived cone photoreceptors and an adult Müller glia cell line. This work provides an important reference with unprecedented insights into the transcriptional landscape of human retinal cells, which is fundamental to understanding retinal biology and disease.
Synopsis
The transcriptome of human neural retina at a single‐cell level defines the gene expression profile in major cell types in the neural retina and can be used as a benchmark to assess the quality of stem cell‐derived cells or primary retinal cells.
The presented transcriptome atlas of human neural retina comprises single‐cell RNA‐sequencing data from 20,009 human retinal cells.
Unsupervised cell clustering analysis allows identification of 18 transcriptionally distinct cell populations that represent all known neural retinal cell types.
Reduced expression of the long non‐coding RNA MALAT1 correlates with longer post‐mortem time in putative early degenerating rod photoreceptors.
The retina transcriptome atlas can be used to benchmark pluripotent stem cell‐derived cone photoreceptors and an adult Müller glia cell line.
A comprehensive analysis of the human retinal transcriptome at a single‐cell level defines gene expression profiles of all major retinal cell types.
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