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Changqiang Chen,1,* Pu Li,1,* Jiuming Chen,1,* Chunxiao Liu,2 Xiaodan Wang,3 Jialin Cai,4 Enfei Xiang,4 Zhidong Gu,1,5 Peizhan Chen4 1Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Neurology & Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Clinical Research Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 5Department of Laboratory Medicine, Ruijin-Hainan Hospital, Shanghai Jiao Tong University School of Medicine (Hainan Boao Research Hospital), Hainan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peizhan Chen, Clinical Research Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201821, People’s Republic of China, Tel +86 13918550745, Email pzchen@me.com Zhidong Gu, Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201821, People’s Republic of China, Tel +86 13801653534, Email guzhidongruijin@163.comPurpose: Vitamin D, an essential nutrient and a pleiotropic steroid hormone, has been reported to be associated with the risk and severity in patients infected with Coronavirus Disease-2019 (COVID-19). The role of vitamin D in predicting clinical outcome for COVID-19 patients is unknown. Here, we aimed to determine the prognostic value of plasma 25(OH)D level in COVID-19 patients.Patients and Methods: A total of 158 patients infected with novel COVID-19 Omicron variants in Shanghai were recruited in this study and were categorized into three groups by the tertile levels of plasma 25(OH)D. Plasma 25(OH)D level was determined along with routine blood tests related to liver and renal functions in newly diagnosed COVID-19 patients at admission. The nucleic acid negative conversion time of throat swab samples was evaluated as the primary clinical outcome. The prognostic value of clinical characteristics and plasma 25(OH)D level was assessed using the Kaplan–Meier plot and Cox proportional hazards regression tests.Results: Higher level of plasma 25(OH)D level in COVID-19 patients was independently associated with shorter nucleic acid negative conversion time from COVID-19 infection (multivariate adjusted HR: 0.54, 95%CI: 0.35– 0.82, P=0.004, tertile 2 vs 1; multivariate adjusted HR: 0.60, 95%CI: 0.39– 0.90, P=0.014, tertile 3 vs 1).Conclusion: Plasma 25(OH)D level may serve as an independent prognostic factor in COVID-19 patient. Our findings indicate the protective roles of vitamin D supplementation in the regiment of patients with COVID-19.Keywords: SARS-CoV-2, COVID-19, plasma 25(OH)D level, nucleic acid negative conversion time

Colloidally prepared core@shell nanoparticles (NPs) were converted to monodisperse high entropy alloy (HEA) NPs by annealing, including quinary, senary, and septenary phases comprised of PdCuPtNi with Co, Ir, Rh, Fe, and/or Ru. Intraparticle heterogeneity, i.e., subdomains within individual NPs with different metal distributions, was observed for NPs containing Ir and Ru, with the phase stabilities of the HEAs studied by atomistic simulations. The quinary HEA NPs were found to be durable catalysts for the oxygen reduction reaction, with all but the PdCuPtNiIr NPs presenting better activities than commercial Pt. Density functional theory (DFT) calculations for PdCuPtNiCo and PdCuPtNiIr surfaces (the two extremes in performance) found agreement with experiment by weighting the adsorption energy contributions by the probabilities of each active site based on their DFT energies. This finding highlights how intraparticle heterogeneity, which we show is likely overlooked in many systems due to analytical limitations, can be leveraged toward efficient catalysis.

Lateral multiheterostructures with spatially modulated bandgaps have great potential for applications in high-performance electronic, optoelectronic and thermoelectric devices. Multiheterostructures based on transition metal tellurides are especially promising due to their tunable bandgap in a wide range and the rich variety of structural phases. However, the synthesis of telluride-based multiheterostructures remains a challenge due to the low activity of tellurium and the poor thermal stability of tellurium alloys. In this work, we synthesized monolayer WSe2−2xTe2x/WSe2−2yTe2y (x > y) multiheterostructures in situ using chemical vapor deposition (CVD). Photoluminescence analysis and Raman mapping confirm the spatial modulation of the bandgap in the radial direction. Furthermore, field-effect transistors with the channels parallel (type I) and perpendicular (type II) to the multiheterostructure rings were fabricated. Type I transistors exhibit enhanced ambipolar transport, due to the low energy bridges between the source and drain. Remarkably, the photocurrents in type I transistors are two orders of magnitude higher than those in type II transistors, which can be attributed to the fact that the photovoltaic photocurrents generated at the two heterojunctions are summed together in type I transistors, but they cancel each other in type II transistors. These multiheterostructures will provide a new platform for novel electronic/photonic devices with potential applications in broadband light sensing, highly sensitive imaging and ultrafast optoelectronic integrated circuits.

Circulating microRNAs (miRNAs) can be used as noninvasive biomarkers and are also found circulating in body fluids such as blood. Dysregulated miRNA expression is associated with many diseases, including non-small cell lung cancer (NSCLC), and the miRNA assay is helpful in cancer diagnosis, prognosis, and monitoring. In this work, a versatile electrochemical biosensing system is developed for miRNA detection by DNAzyme-cleavage cycling amplification and hybridization chain reaction (HCR) amplification. With cleavage by Mn

Milled corn cobs were hydrolyzed with 50 mM H2SO4 resulting in a hydrolysate rich in solubilized pentose sugars and particulate aromatic oligomers from the hemicellulose portion of the corn cobs. Following centrifugation to remove the solids, the acidic supernatant was treated under hydrodeoxygenation conditions of 3.5–7 MPa H2 at 160 °C with supported Rh, Pt, and Pd catalysts. Supports examined were alumina, silica-alumina, and the zeolites ZSM-5 and Beta. All three metals supported on the zeolites were more effective in producing 1-hydroxy-2-pentanone (HPO) than they were when supported on the mesoporous aluminas. Ultimately, 2 wt% Pd/Beta was chosen for further study and development. The selectivity to HPO was 90% and the yield was 10–14% of the starting mass of cob. With repeated use of the catalyst, the selectivity was unchanged but the yield fell as decreased activity allowed pentose dehydration to furfural to increase. It was found that addition of La to the support decreased the loss of activity substantially. The catalysts were characterized by gas sorption analysis, powder XRD, XPS, STEM-EDS, and H2-TPR. The reaction mechanism was probed using 13C-xylose as substrate.

Heterogeneous materials with spatially modulated bandgaps have many unique applications, such as super-broadband nanolasers, color engineered displays, hyperspectral detectors, and full spectrum solar cells. In this work, spatially composition-graded WSe2 − 2xTe2x flakes are synthesized through an in situ chemical vapor deposition method. Furthermore, a monolayer flake topography is confirmed by atomic force microscopy. Photoluminescence and Raman line-scanning characterization indicate the bandgap changes continuously from center (1.46 eV) to edge (∼1.61 eV) within a monolayer flake. Electronic devices based on this spatially composition-graded material exhibit tunable transfer curves. First principal calculation reveals that the electron affinity increases, while the bandgap decreases based on tellurium composition. This is consistent with experimentally observed non-monotonic dependence of the hole current on tellurium composition. This work provides the experimental groundwork for synthesis of the composition-graded transition metal dichalcogenide materials and offers a route toward tailoring their electrical properties by bandgap engineering in the future.

Precipitation pathways in many nickel-based superalloys are highly complex and in some cases proceed very slowly. This behavior has hampered their introduction into some novel application spaces ranging from microelectromechanical systems (MEMS) to protective coatings, wherein their high temperature strength and oxidation resistance would otherwise be highly desirable. In this investigation, the microstructure of Ni-25Mo-8Cr superalloy thin films prepared via direct current magnetron sputtering (DCMS) is shown to be key to manipulating and understanding phase transformations. Specifically, the columnar, highly textured, and nanotwinned grains are shown to facilitate precipitation of the equilibrium DOa (Ni3Mo) phase during a mild heat treatment. Conversely, elimination of the nanotwins through a two-step heat treatment leads to precipitation of metastable Ni2(Mo,Cr) (isomorphous with Pt2Mo and Ni2Cr) precipitates. The straightforward capacity to select one of several possible phase transformation pathways presents an opportunity to create precisely tuned microstructures specific to the desired application, while simultaneously providing unprecedented insight on these complex phase transformations.

Supplemental Digital Content is available in the text, Observational studies have reported that childhood obesity is positively associated with risks of type 2 diabetes (T2D) and coronary artery disease (CAD) in adults; however, whether this association is causal is still unclear. In the present study, we conducted the 2-sample Mendelian randomization (MR) studies to investigate whether childhood obesity is causally associated with T2D and CAD in adults. Seven single-nucleotide polymorphisms (SNPs) that significantly associated with childhood obesity were used as instrumental variables. The 2-sample MR analyses were performed with the summary-level data of large-sample genome-wide association studies to evaluate the causal effects of childhood obesity on adult T2D and CAD and the levels of cardiometabolic traits. The 2-sample MR analyses suggested that each 1-unit increase in the log-odds of having childhood obesity was causally associated with an increased risk of adult T2D (odds ratio [OR] = 1.16, 95% confidential interval [CI] = 1.06–1.28; P = 1.0 × 10–3) and CAD (OR = 1.07, 95% CI = 1.02–1.12; P = 4.0 × 10–3) based on the inverse-variance weighted method. The MR analyses also suggested that childhood obesity was positively associated with the levels of adult body mass index, waist circumference, hip circumference, waist and hip ratio, log-transformed fasting glucose, log-transformed homeostatic model assessment (HOMA) of insulin resistance (%), and triglycerides. The childhood obesity was negatively associated with the adult high-density lipoprotein cholesterol level; however, there was no evidence of a causal association between childhood obesity and the levels of fasting glucose, 2-hour glucose, HbA1c (%), log-transformed HOMA of ß-cell function (%), low-density lipoprotein cholesterol, or total cholesterol in adults. In conclusion, a genetic predisposition to childhood obesity was associated with an increased risk of adult T2D and CAD, providing causal relations between childhood obesity and the risks of T2D and CAD in adults; however, the results need to be validated with larger-scale intervention studies.

Bismuth vanadate (BiVO4) is considered one of the most successful candidates to be used as photoanode for solar-to-hydrogen conversion. However, its relatively high recombination rates and considered low long-term stability limits its applicability. Doping BiVO4 with tungsten and developing heterojunctions with inorganic perovskites has emerged as strategies to overcome these issues. However, the development of these materials requires plenty of time and energy. Here, we reported the development of a new synthetic method to prepare heterojunctions of tungsten-doped bismuth vanadate (using 1, 3 and 5 % in mass of W) and tungsten oxide. The heterojunctions were prepared in a one-pot microwave-assisted method that takes only 24 min. Photocatalytic efficiency was determined through quantification of the amount of hydroxyl radical, generated by the catalysts when they are irradiated with simulated sunlight, and through photoelectrochemical experiments. The heterojunctions showed enhanced photocatalytic activity, which was ascribed to the adequate alignment of the band edges potentials of the semiconductors. Also, the tungsten doping decreases the recombination rates. Both effects increase the photogenerated charges lifetime.

Congenital hypopituitarism (CH) is a relatively rare disease that is characterized by the deficiency of one or more hormones secreted by the pituitary gland, which leads to metabolic disorders, amenorrhea and infertility. However, the underlying molecular mechanisms of CH have not yet been fully elucidated. The present study evaluated the genome‑wide methylation level of whole blood DNA in 12 patients with CH and 12 age‑matched controls using Illumina Human Methylation 450 array, in order to determine the roles of epigenetic regulation in the pathogenesis of CH. The results demonstrated that the methylation levels of 51 CpG sites were significantly different between the patients with CH and the controls. Functional enrichment analysis identified that the aberrant methylated genes were enriched in gene sets associated with metabolic or cellular process, immune system process and reproduction. In addition, two CpG sites on genes LIM domain kinase 2 (LIMK2) and piwi‑like RNA‑mediated gene silencing 2 (PIWIL2), which are involved in spermatogenesis and/or testicular development, were identified to be hypermethylated in male patients with CH. The hypermethylation of these sites was further validated in another 40 patients with CH and 40 matched controls with a quantitative bisulfite pyrosequencing method, and the methylation levels of these two loci demonstrated promising diagnostic capacities for CH. The present results suggested that aberrant methylation of genes may be involved in the pathogenesis of CH, and hypermethylation of LIMK2 and PIWIL2 may contribute to the infertility of male patients with CH. Further studies are required to elucidate the underlying mechanisms of the epigenetic regulation of these genes.

Spinocerebellar ataxia (SCA) is a group of genetic diseases of the nervous system with genetic and clinical heterogeneity. SCA is often caused by an expanded CAG repeat sequence in the encoding protein. Genetic testing is necessary to diagnose and classify the types of SCA. Next‑generation DNA sequencing usually generates a high error rate for insertion or deletion mutations, so it is unhelpful for classifying the types of SCA. In the present study, a Chinese SCA pedigree was preliminarily diagnosed with SCA1 using polymerase chain reaction (PCR) amplification. The propositus and his three younger siblings were diagnosed with SCA1 as a result of the identification of the length of the expanded CAG repeat sequence in the ATXN1 gene performed using Sanger sequencing. The current study presents a convenient and efficient method to identify causative mutations for polyglutamine SCA using PCR amplification followed by Sanger sequencing.

Ultraviolet emission characteristics of cubic (c-) GaN enabled through hexagonal-to-cubic phase transition are reported. Substrate patterning and material growth are shown to affect phase purity and emission characteristics of c-GaN as studied by electron backscatter diffraction, and photo- and cathodoluminescence, respectively. Raman study shows a tensile strain in the c-GaN. Time-resolved photoluminescence reveals c-GaN band edge emission decay time of 11 ps. The ultraviolet emissions from both phases of GaN are linearly polarized in the same direction, which is along the ⟨112̅0⟩ and ⟨110⟩ directions of hexagonal GaN and c-GaN, respectively. Temperature-dependent (5.7 to 280 K) cathodoluminescence studies reveal an internal quantum efficiency of ~29% at room temperature along with intrinsic and extrinsic defect energy levels of ~124 and ~344 meV, respectively, of the phase-transition c-GaN. Using the IQE value and carrier decay lifetime, a radiative lifetime of 38 ps is extracted. Overall, photonic properties of phase-transition c-GaN and their dependence on substrate patterning and material growth are reported.

Here, bioinformatics data from Sirt1 knock-out (KO) and knock-in (KI) mice suggest that Sirt1 inhibits Wnt/βCatenin signaling in the liver. However, it is unclear how this relationship occurs and how it contributes to malignant phenotypes in liver cancer cells. We found that Sirt1 expression promotes phosphorylation of βCatenin at Ser675, which may subsequently decrease expression of total-βCatenin. Mechanistically, Sirt1 expression elevates phosphorylation of the alpha subunit of protein kinase A (PKAα), and this event is essential for Sirt1-induced phosphorylation of βCatenin. The negative effects of Sirt1 on βCatenin stability are also dependent on PKAα. Stimulating PKAα recruits βTrCP, a well-known ubiquitin E3 ligase for βCatenin, to βCatenin. Interestingly, Sirt1 expression is able to up-regulate βTrCP expression. Finally, we found that malignant phenotypes occur in hepatocytes when Sirt1 and βCatenin are co-overexpressed, and such effects are enhanced by simultaneous knockdown of PKAα. In contrast, malignant phenotypes are abrogated upon knockdown of Sirt1, and this phenotype is magnified by knockdown of βCatenin. Collectively, we conclude that suppression of both Sirt1 and Wnt/βCatenin might be effective in treating liver cancer.

Plate impact shock and spall recovery experiments were conducted to study the effects of peak shock stress on the substructure evolution and spall response of fully annealed 1100 aluminum. The substructure of the material evolves substantially with increase in peak shock stress ranging from 4 GPa to 9 GPa with dislocation debris uniformly distributed throughout the interior of the subgrain. Observations from substructure evolution in conjunction with spall failure results suggest that ductile fracture by void nucleation, growth, and coalescence was perhaps the dominant fracture mode for shock stresses up to approximately 8.3 GPa. Whereas, beyond 8.3 GPa the material softened possibly due to dislocation reorganization (dynamic recovery) and brittle intergranular fracture by decohesion with isolated pockets of nanovoids was perhaps the dominant fracture mode. The contributions of nanovoids to the dynamic recovery process, if any, were unresolved. Microhardness measurements show an increase in residual hardness throughout the shock stress range studied implying shock hardening up to approximately 8.3 GPa. This observation also suggests that thermal softening was not operative throughout the shock stress range studied. However, dynamic recovery was thermally influenced during shock loading.

Mechanical twinning has been introduced into a body-centered cubic metal, tantalum, through shear-dominant dynamic loading at a high shear strain rate (up to 3 × 104/s) at 77 K. Direct measurement of shear stress combined with transmission electron microscopy (TEM) confirmed the occurrence of deformation twinning at applied global shear stresses of 520 MPa and above. The TEM characterization was focused on nanometer-sized individual twins that are interspersed and aligned in association with slip bands. These small twins belong to the {1 1 2} 〈 1 1 1 ¯ 〉 twinning system but show unusual morphologies and growth characteristics, and are believed to be incipient twins at the early stages of their development. TEM analysis revealed a multifaceted growth characteristic of the incipient twins following at least two {1 1 2} planes in the 〈 1 1 1 ¯ 〉 zone. While the formation of a macroscopic twin is a result of growth and coalescence of an array of small twins, the early stage growth of an incipient twin is rationalized through a slip-assisted double-cross-slip growth mechanism.

We examine the thermodynamics of phase separation and ordering in the ternary Ca(x)Pb(1-x)S and Sr(x)Pb(1-x)S systems by density-functional theory combined with a cluster expansion and Monte Carlo simulations. Similar to most other ternary III-V or IV-VI semiconductor alloys, we find that bulk phase separation is thermodynamically preferred for PbS-CaS. However, we predict the surprising existence of stable, ordered ternary compounds in the PbS-SrS system. These phases are previously unreported ordered rocksalt-based compounds: SrPb3S4, SrPbS2, and Sr3PbS4. The stability of these predicted ordered phases is confirmed by transmission electron microscopy observations and band gap measurements. We believe this work paves the way for a combined theory-experiment approach to decipher complex phase relations in multicomponent chalcogenide systems.

The influence of hierarchical TiO2 inclusions on electrical and thermal transport properties has been investigated in the Ba-filled skutterudite compound Ba0.3Co4Sb12 synthesized by ball milling followed by hot pressing. The hierarchical TiO2, with the morphology of nanocrystallite aggregates, was prepared using a carbon sphere-templated method. It was found that TiO2 inclusions strongly enhance the Seebeck coefficient while they weakly degrade the electric conductivity. In addition, TiO2 inclusions reduce significantly the lattice thermal conductivity through all-scale length phonon scattering due to the hierarchically-structured TiO2 particles. ZT values up to 1.2 were obtained for Ba0.3Co4Sb12 with an optimal amount and dispersion of TiO2 inclusions. These observations demonstrate an exciting scientific opportunity to raise the figure-of-merit of filled skutterudites via hierarchical dispersion.

Focal adhesion kinase (FAK) regulates cell adhesion, migration, proliferation, and survival. We identified a novel splicing mutant, FAK-Del33 (exon 33 deletion, KF437463), in both breast and thyroid cancers through colony sequencing. Considering the low proportion of mutant transcripts in samples, this mutation was detected by TaqMan-MGB probes based qPCR. In total, three in 21 paired breast tissues were identified with the FAK-Del33 mutation, and no mutations were found in the corresponding normal tissues. When introduced into a breast cell line through lentivirus infection, FAK-Del33 regulated cell motility and migration based on a wound healing assay. We demonstrated that the expression of Tyr397 (main auto-phosphorylation of FAK) was strongly increased in FAK-Del33 overexpressed breast tumor cells compared to wild-type following FAK/Src RTK signaling activation. These results suggest a novel and unique role of the FAK-Del33 mutation in FAK/Src signaling in breast cancer with significant implications for metastatic potential.

Deformation twinning was introduced in Ta through dynamic compression shear and uniaxial compression at high strain rates up to ∼10 4 s −1 at low temperatures. Under dominant shear, the specimens showed continuous strain softening at high rates, and the deformation twins showed anomalous and highly irregular morphologies. Under compression, deformation twins appeared as typical straight and thin plates accompanied by considerable strain hardening in mechanical response. The results are correlated with the interplay of slip and deformation twinning unique for body-centered cubic metals.

PTPRA is reported to be involved in cancer development and progression through activating the Src family kinase (SFK) signaling pathways, however, the roles of PTPRA in the squamous cell lung cancer (SCC) development are unclear. The purpose of this study was to clarify the clinical relevance and biological roles of PTPRA in SCC. We found that PTPRA was upregulated in squamous cell lung cancer compared to matched normal tissues at the mRNA (N=20, P=0.004) and protein expression levels (N=75, P

Uniaxial quasi-static, uniaxial dynamic and confined dynamic compression experiments have been performed to characterize the failure and deformation mechanisms of a sintered polycrystalline aluminum nitride using a servohydraulic machine and a modified Kolsky bar. Scanning electron microscopy and transmission electron microscopy (TEM) are used to identify the fracture and deformation mechanisms under high rate and high pressure loading conditions. These results show that the fracture mechanisms are strong functions of confining stress and strain rate, with transgranular fracture becoming more common at high strain rates. Dynamic fracture mechanics and micromechanical models are used to analyze the observed fracture mechanisms. TEM characterization of fragments from the confined dynamic experiments shows that at higher pressures dislocation motion becomes a common dominant deformation mechanism in AlN. Prismatic slip is dominant, and pronounced microcrack–dislocation interactions are observed, suggesting that the dislocation plasticity affects the macroscopic fracture behavior in this material under high confining stresses.

The dynamic multiaxial response of hot-pressed AlN is characterized through quasi-static uniaxial compression, dynamic uniaxial compression and dynamic confined compression experiments within the strain rate range of 10−3–103 s−1. Real-time visualization shows the failure patterns change from axial splitting under uniaxial dynamic compression to shear faulting under confinement. The compressive strength is moderately sensitive to both the confining stress and the loading rate. Post-mortem fracture surface studies show that the dominant fracture mechanism remains transgranular fracture under all loading conditions.

Nanosized pillars with diameters ranging from 90 to 600 nm of four amorphous alloys, Cu47Ti33Zr11Ni6Sn2Si1, Zr50Ti16.5Cu15Ni18.5, Zr61.8Cu18Ni10.2Al10 and Al86Ni9Y5, were fabricated and tested in situ in a transmission electron microscope. The major consideration when varying the composition was the change in bulk modulus and Poisson's ratio, which may affect the deformation mode and ductility of metallic glasses (MGs) at the nanoscale. Differences between the deformation behavior of tapered (1.5-3 degrees) and taper-free systems were also investigated. The yield stress of all the MGs measured through the in situ experiments is found to be essentially size independent, irrespective of tapering. With increasing size, all the MGs examined show a ductile-to-brittle transition under compression; the transition point, however, depends on the chemical composition of the specific MG investigated. The lower the mu/B ratio, the larger the pillar diameter above which more brittle behavior occurs. Al86Ni9Y5 taper-free MG showed a transition threshold to brittle behavior at the largest pillar diameter of 300 nm. A micromechanical model is presented to explain the various dependencies. (C) 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

CD166/ALCAM plays an important role in tumor aggression and progression as well as protecting cancer cells against apoptosis and autophagy. However, the mechanism by which pro-cell death signals control CD166 expression remains unclear. Here we show that following serum deprivation (SD), upregulation of CD166 protein is shorter than that of CD166 mRNA. Molecular analysis revealed both CD166 and miR-9-1 as two novel NF-κB target genes in hepatoma cells. In vivo activation and translocation of the NF-κB P50/P65 hetero-dimer into the nucleus following the phosphorylation and accompanied degradation of its inhibitor, IκBα, contributes to efficient transcription of both genes following SD. We show that following serum starvation, delayed up-regulation of miR-9 represses translation of CD166 protein through its target sites in the 3′-UTR of CD166 mRNA. We also propose that miR-9 promotes cell migration largely due to inhibition of CD166. Collectively, the study elucidates a novel negative auto-regulatory loop in which NF-κB mediates differential regulation of CD166 after SD.

Both quantitative stress-strain curves and in situ transmission electron microscope observations demonstrate intrinsically strong sample size effects on the deformation mode of taper-free metallic glass pillars. With the pillar diameter gradually decreasing from 640 to 70 nm, the deformation mode evolves from (i) highly localized and catastrophic shear banding to, (ii) initially nonlocalized deformation developing toward stop-and-go shear banding accompanied by softening, (iii) apparently homogeneous and banding-less deformation but with intermittent shear events, and eventually (iv) fully homogeneous and smooth plastic flow.

RAB25 plays an important role in tumor progression and aggressiveness; altered RAB25 expression may cause human cancer. As the underlying mechanism of RAB25-mediated carcinogenesis in various tumor types progressively comes to light, RAB25 is expected to represent a novel therapeutic target. However, the regulation of RAB25 expression per se has not yet been described. Here we have firstly identified and characterized the human RAB25 promoter. Using PCR-based chromatin accessibility and chromatin immunoprecipitation (ChIP) assays, an open chromatin conformation (−173/+17) was detected around the transcription start site of the RAB25 gene. Deletion constructs of the 5′ flanking region were fused to a luciferase reporter gene. After transient transfection in gastric cancer cell line AGS, a CRE (−67/−58) binding CREB was identified in the core promoter region. Electrophoretic mobility shift (EMSA) and ChIP assays demonstrated that CREB binds to the core promoter. Deletion of CREB consensus sequence resulted in the total loss of the promoter activity. Moreover, we have also found forskolin, PKA activator, could enhance open chromatin accessibility, by which to expose the CRE and facilitate phosphorylation of CREB, which in turn recruits co-factor CBP and Brg I and then results in a more open chromatin configuration associated with local histone modification, finally heightening RAB25 expression and strengthening its promoter activity. Therefore, the present study delineates the fundamental elements of a core promoter structure that will be helpful for future studies regarding the regulation of RAB25 gene.

Surface smoothness of diamond-like carbon based thin films becomes a crucial property for developing nearly frictionless protective coatings. Surface roughness and the dynamic growth behaviour of TiC/a-C nanocomposite films, deposited by non-reactive pulsed DC (p-DC) sputtering of graphite targets, were studied using atomic force microscopy and cross-sectional scanning electron microscopy. Upon increasing the intensity of concurrent ion impingement by raising the frequency of p-DC sputtering, a transition from dynamic roughening to dynamic smoothing was revealed, leading to a transition from a strong columnar to a columnar free microstructure. It was shown that smooth films can be deposited on initial rough surfaces at a higher pulse frequency (350 kHz). Also dense, tough, ultrasmooth and ultralow friction TiC/a-C: H nanocomposite films were successfully deposited on industrial polished steel substrates by reactive p-DC sputtering of Ti targets at 350 kHz frequency in an argon/acetylene atmosphere.

Rough TiC/a-C films were intentionally grown on smooth surface to simulate a rough finishing of industrial substrates. Surface roughness and growth dynamics of TiC/a-C nanocomposite films deposited on such rough surfaces by non-reactive pulsed-DC (p-DC) sputtering of graphite targets at 350 kHz pulse frequency were studied using atomic force microscopy, cross-sectional scanning electron microscopy. Intensive concurrent ion impingement during the film growth at higher pulse frequency of p-DC sputtering leads to rapid smoothing of such initial rough surfaces. It was shown that rapid smoothing of initially rough surfaces with RMS roughness ~ 6 nm to The observed dynamic smoothing phenomenon was applied to obtain ultra-smooth and ultra-low friction (μ ~ 0.05) TiC/a-C:H nanocomposite films on industrial polished steel substrates by 200 and 350 kHz p-DC sputtering of Ti-targets in an argon/acetylene atmosphere.

Background Monoclonal free light chains (FLC) commonly exist in monomeric or dimeric forms but rarely as larger molecules. Little is known about whether polymeric molecules can affect urine protein electrophoresis (UPE) results. Methods Urine samples were collected from 72 multiple myeloma (MM) patients with Bence Jones protein (BJP). Urine protein and immunofixation electrophoresis were analyzed on Sebia SDS "agarose" gel electrophoresis system (SDS-AGE), and immunoglobulin free light chains were measured on the BNII nephelometric assay. Results A type of disulfide-bound FLC dimer shows a pattern shift to the position of the "albumin" band in urine protein electrophoresis in multiple myeloma (MM) patients according to the Sebia agarose gel-based detection system, which was validated by immunofixation, SDS-PAGE, and mass spectrometric methods. Similar cases were found in 21 (29.17%) of 72 MM patients with BJP, and 19 (90.5%) of 21 patients were the lambda type. Conclusions These results indicate that BJP with lambda type has a strong tendency to abnormally migrate, which may increase the risk of misinterpretation of protein electrophoresis in clinics. Thus, when the urine protein electrophoresis is inconsistent with the result by nephelometric method, urine protein electrophoresis needs to be repeated on the deduced condition to confirm the essence of the originally identified "albumin."

This paper reports several new findings on the breakdown of dynamic roughening in thin film growth. With increasing energy flux of concurrent ion impingement during pulsed DC sputtering, a transition from dynamic roughening to dynamic smoothening is observed in the growth behavior of TiC/a-C nanocomposite films. The nanocomposite films show a negative growth exponent and ultra-smoothness (RMS roughness similar to 0.2 nm at a film thickness of 1.5 mu m). Based on high-resolution cross-sectional transmission electron microscopy observations we conclude that during growth an amorphous front layer of 2 nm covers the nanocomposite film and suppresses the influence of nanocrystallites on the roughness evolution of the nanocomposite films. We were able to predict the evolution of surface roughness based on a linear equation of surface growth which contains two diffusivity parameters that control the atomic mobility along the growing outer surface. The model is in good agreement with atomic force microscopy measurements of roughness evolution. (C) 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

We have fabricated micro-/nano-pillars of two metallic glasses (MGs), Cu-based Cu(47)Ti(33)Zr(11)Ni(6)Sn(2)Si(1) and Zr-based Zr(50)Ti(16.5)Cu(15)Ni(18.5), respectively, with pillar tip diameters ranging from similar to 650 to similar to 90 nm. These pillars were mechanically tested in situ in transmission electron microscopy as a function of pillar diameters. It turns out that the yield strengths of both MGs are close to those of the bulk glasses and are essentially size independent. Statistical physics description of strength for small size metallic glass is discussed.

This paper concentrates on the deformation behavior of amorphous diamondlike carbon composite materials. Combined nanoindentation and ex situ cross-sectional transmission electron microscopy investigations are carried out on TiC/a-C nanocomposite films, with and without multilayered structures deposited by pulse dc magnetron sputtering. It is shown that by controlling the distribution of nanocrystallites forming nanoscale multilayers, the system can be used as a "microstructural ruler" that is able to distinguish various deformation patterns, which can be hardly detected otherwise in a homogeneous structure. It is shown that rearrangement of nanocrystallites and displacement of a-C matrix occur at length scales from tens of nanometer down to 1 nm. At submicrometer scale homogeneous nucleation of multiple shear bands has been observed within the nanocomposites. The multilayered structure in the TiC/a-C nanocomposite film contributes to an enhanced toughness.

In this paper, we report some striking results on the microstructural control of TiC/a-C nanocomposite coatings with pulsed direct current (DC) magnetron sputtering. The interface morphology and microstructure evolution as a function of pulse frequency and duty cycle were scrutinized using atomic force microscopy, scanning electron microscopy and high-resolution transmission electron microscopy techniques. It is shown that, with increasing pulse frequency, the nanocomposite coatings exhibit evolutions in morphology of the growing interface from rough to smooth and in the microstructure from strongly columnar to fully columnar-free. In addition, the smoothly growing interface favors the formation of a tailor-made multilayered nanocomposite structure. The fundamental mechanisms are analyzed with the assistance of plasma diagnostic experiments. Ion mass/energy spectrometry measurements reveal that, depending on the frequency and duty cycle of DC pulses, pulsing of the magnetrons can control the flux and energy distribution of Ar+ ions over a very broad range for concurrent impingement on the growing interface of deposited coatings, in comparison with DC sputtering. The significantly enhanced energy flux density is thought to be responsible for the "adatom transfer" in interface smoothening and thus the restraint of columnar growth. (C) 2007 Acta Materialia, Inc. Published by Elsevier Ltd. All rights reserved.

The deformation and fracture behaviors of delta hydrides in cyclic strained titanium containing 350, 720 and 930 ppm hydrogen were investigated and compared to that of gamma hydrides in 77 ppm hydrogen specimens. It was found that the gamma and delta hydrides, respectively, in 77 and 350 ppm hydrogen specimens could be plastically deformed readily along with the matrix without fracture, while the delta hydrides at hydrogen contents more than 720 ppm can be either plastically deformed or cleavage fractured, depending on their sizes, orientations. and interactions with localized matrix deformation. The crystallographic, microstructural and micromechanical mechanisms for hydride behavior were discussed. (C) 2004 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The dislocation configurations and their interactions with γ-hydrides were investigated in cyclically strained titanium containing 77 ppm hydrogen. At least three sets of dislocations could be activated in hydride precipitates. To accommodate the inhomogeneous strain between the matrix and the hydrides a crystal rotation, which is a rotation about the [001]γ//[0001]α axis, occurred in both of them. Accordingly cell structures with misorientations up to 10° about the same [0001]α axis formed in the matrix near the interface. A mechanism for the crystal rotation and cell formation was proposed. Also hydride dissolution and strain-induced hydrides were observed at the intersections of slip bands with hydrides, and this was considered to be a process controlled by the hydrogen-transport effect of slipping dislocations.

Two types of gamma hydride precipitates with the same structure were observed in coarse-grained commercially pure titanium containing about 77 ppm hydrogen. The interactions of slipping and twinning with both types of hydrides under cyclic straining were observed using SEM and TEM. It was found that the type-I gamma hydrides can be plastically deformed and even ultimately fragmented by a slip mechanism with no voids formed under cyclic plastic deformation. In contrast type-II gamma hydrides were difficult to be plastically deformed. The crystallographic mechanisms for the plastic deformation of hydrides are discussed. (C) 2002 Acta Materialia Inc. Published by Elsevier Science Ltd. All rights reserved.

Protein tyrosine phosphatase (PTP)‑α regulates the phosphorylation of focal adhesion kinase (FAK), which is important in cellular signal transduction and integration of proteins. It has been demonstrated that a FAK‑Del33 mutation (deletion of exon 33; KF437463) in breast cancer tissues regulates cell migration through FAK/Src signaling activation. However, the detailed pathway for Src activation with FAK‑Del33 remains to be elucidated. The present study used a retroviral expression system to examine changes in PTPα phosphorylation affected by the FAK‑Del33 protein in breast cancer cells. Small interfering (si)RNA targeting PTPα interfered with the phosphorylation of Src. Wound‑healing and migration assays were performed to identify cell morphology and quantitative analysis was performed by examining band color depth in western blot analysis. Significant differences were observed in the phosphorylation level of PTPα at Tyr789 between the FAK‑Del33 and the wild‑type breast cancer cells, suggesting that FAK regulated the phosphorylation level of PTPα at Tyr789 in breast cancer mutant FAK‑Del33 cells. The gene expression profile with FAK siRNA did not alter the levels of phosphorylation in other mutants, including autophosphorylation disability (Y397F), ATP kinase dominant negative (K454R) and protein 4.1, ezrin, radixin, moesin domain attenuate (Δ375). FAK RNAi inhibited the activity of the FAK‑Del33 at the Src site and rescued the elevated cell migration and invasion. The present study demonstrated for the first time, to the best of our knowledge, an increase in the phosphorylation level of PTPα‑Tyr789 by its upstream activator, FAK‑Del33, leading to Src activation in certain breast cancer cells, which has significant implications for metastatic potential.

The existence of new ordered rocksalt-based compounds SrPb3S4, SrPbS2, and Sr3PbS4 in the title system is predicted by DFT calculations, and experimentally confirmed by TEM and band gap measurements.