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Recent studies have reported the experimental discovery that nanoscale specimens of even a natural material, such as diamond, can be deformed elastically to as much as 10% tensile elastic strain at room temperature without the onset of permanent damage or fracture. Computational work combining ab initio calculations and machine learning (ML) algorithms has further demonstrated that the bandgap of diamond can be altered significantly purely by reversible elastic straining. These findings open up unprecedented possibilities for designing materials and devices with extreme physical properties and performance characteristics for a variety of technological applications. However, a general scientific framework to guide the design of engineering materials through such elastic strain engineering (ESE) has not yet been developed. By combining first-principles calculations with ML, we present here a general approach to map out the entire phonon stability boundary in six-dimensional strain space, which can guide the ESE of a material without phase transitions. We focus on ESE of vibrational properties, including harmonic phonon dispersions, nonlinear phonon scattering, and thermal conductivity. While the framework presented here can be applied to any material, we show as an example demonstration that the room-temperature lattice thermal conductivity of diamond can be increased by more than 100% or reduced by more than 95% purely by ESE, without triggering phonon instabilities. Such a framework opens the door for tailoring of thermal-barrier, thermoelectric, and electro-optical properties of materials and devices through the purposeful design of homogeneous or inhomogeneous strains. [ABSTRACT FROM AUTHOR]

Experimental discovery of ultralarge elastic deformation in nanoscale diamond and machine learning of its electronic and phonon structures have created opportunities to address new scientific questions. Can diamond, with an ultrawide bandgap of 5.6 eV, be completely metallized, solely under mechanical strain without phonon instability, so that its electronic bandgap fully vanishes? Through first-principles calculations, finite-element simulations validated by experiments, and neural network learning, we show here that metallization/demetallization as well as indirect-to-direct bandgap transitions can be achieved reversibly in diamond below threshold strain levels for phonon instability. We identify the pathway to metallization within six-dimensional strain space for different sample geometries. We also explore phonon-instability conditions that promote phase transition to graphite. These findings offer opportunities for tailoring properties of diamond via strain engineering for electronic, photonic, and quantum applications. [ABSTRACT FROM AUTHOR]

Nanoscale specimens of semiconductor materials as diverse as silicon and diamond are now known to be deformable to large elastic strains without inelastic relaxation. These discoveries harbinger a new age of deep elastic strain engineering of the band structure and device performance of electronic materials. Many possibilities remain to be investigated as to what pure silicon can do as the most versatile electronic material and what an ultrawide bandgap material such as diamond, with many appealing functional figures of merit, can offer after overcoming its present commercial immaturity. Deep elastic strain engineering explores full six-dimensional space of admissible nonlinear elastic strain and its effects on physical properties. Here we present a general method that combines machine learning and ab initio calculations to guide strain engineering whereby material properties and performance could be designed. This method invokes recent advances in the field of artificial intelligence by utilizing a limited amount of ab initio data for the training of a surrogate model, predicting electronic bandgap within an accuracy of 8 meV. Our model is capable of discovering the indirect-to-direct bandgap transition and semiconductor-to-metal transition in silicon by scanning the entire strain space. It is also able to identify the most energy-efficient strain pathways that would transform diamond from an ultrawidebandgap material to a smaller-bandgap semiconductor. A broad framework is presented to tailor any target figure of merit by recourse to deep elastic strain engineering and machine learning for a variety of applications in microelectronics, optoelectronics, photonics, and energy technologies. [ABSTRACT FROM AUTHOR]

The present study aimed to detect early changes in the concentration of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in a rat model of brain injury combined with traumatic heterotopic ossification (HO). A total of 132 male Sprague-Dawley rats were used to establish the experimental and control groups. Anatomy and sample collection were conducted on postoperative days 1, 2, 3, 4, 5, 6 and 7. Hematoxylin and eosin and immunohistochemical staining were performed for local tissues. MMP-9, MMP-2 and TIMP-1 levels and gene expression level were measured by ELISA and reverse transcription-quantitative polymerase chain reaction. Radiological investigation of the rat lower limbs was conducted at weeks 5 and 10 following modeling to observe the occurrence of HO. The incidence of HO for rats in the experimental group was higher compared with the control group. The serum MMP-9 levels of the experimental group were notably higher on postoperative days 5-7 compared with the control group. The MMP-9 gene expression of the experimental group was higher on postoperative days 3-7 compared with the control group. The TIMP-1 gene expression levels were markedly higher compared with the control group at each time point. Thus, an increase in inflammatory response is closely associated with brain injury, in addition to an increase in the number of inflammatory cells with the incidence of HO. The pathological elevation of MMP-9 and the altered dynamic equilibrium between MMP-9 and TIMP-1 contributed to the degradation, remodeling and calcification of the extracellular matrix, resulting in the induction of osteoblast precursor cells in HO. MMP-9 is a predictive marker of HO. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are a class of ubiquitous persistent environmental pollutants which are primarily formed from the incomplete combustion of organic materials. Many potential sources of human exposure to PAHs exist, including daily exposures from the ambient environment or occupational settings. PAHs have been found to cause harmful effects on human health. Here, we evaluated the adverse effects of pyrene, a common PAH, on the liver. The present study demonstrates that pyrene is able to activate mouse constitutive androstane receptor (CAR). CAR protein, as measured by Western blot analysis, was observed to translocate into the nucleus from the cytoplasm in mouse liver after exposure to pyrene. Utilizing CAR null mice, we identified that CAR mediates pyrene-induced hepatotoxicity. Increased relative liver weight, hepatocellular hypertrophy, and elevated serum alanine aminotransferase levels were found in wild-type but not CAR null mice after orally administered pyrene. We further show that pyrene induced the expression of mouse liver metabolism enzymes including CYP2B10, CYP3A11, GSTm1, GSTm3, and SULT1A1, and caused hepatic glutathione depletion in wild-type but not CAR null mice. Moreover, by luciferase reporter assay and quantitative real-time PCR analysis, pyrene was found to be a potential inducer of CYP2B6 expression via activation of human CAR in HepG2 cells and human primary hepatocytes. Our observations suggest that pyrene is a novel CAR activator and that CAR is essential for mediating pyrene-induced liver injury. [ABSTRACT FROM AUTHOR]

The CYP2C subfamily of cytochrome P450 enzymes is an important class of drug metabolizing enzymes in human liver. CYP2C9 is the most abundant member of the human CYP2C subfamily in liver and metabolizes ~15% of the therapeutic drugs as well as other xenobiotics and endogenous compounds. A number of nuclear receptors including xenobiotic-sensing receptors such as the constitutive androstane receptor (CAR), pregnane X receptor (PXR), and glucocorticoid receptor (GR) as well as liver enriched receptors hepatic nuclear factor 4α (HNF4α) and the estrogen receptor α (ERα) regulate CYP2C9 expression. Here, we show that Med25, a variable component of Mediator complex, enhanced ligand dependent ERα-mediated transcriptional activation of CYP2C9 promoter and interacts with activated ERα by 17β-estradiol through its C-terminal LXXLL motif. In conclusion, Med25 is identified as a new coactivator of ERα that is required for ERα-mediated regulation of CYP2C9 expression. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is cooled to 1 K in a seeded Ar supersonic molecular beam. NO molecules are ionized by one-color two-photon resonant enhanced multiphoton ionization (REMPI) process to form an ultracold plasma. The density of the ionized molecules in the illuminated volume approaches to 1.5 × 1013 cm−3. Prompt electrons, plasma electrons and intact NO+ ions are produced during this process. Experimental results confirm that the lifetime of this ultracold plasma is longer than 18.3 μs. This is the first report of NO ultracold plasma with significant lifetime produced by one-color two-photon REMPI process. [ABSTRACT FROM AUTHOR]

Multi-target drugs against selective multiple targets improve therapeutic efficacy, safety and resistance profiles by collective regulations of a primary therapeutic target together with compensatory elements and resistance activities. Efforts have been made to employ in-silico methods for facilitating the search and design of selective multi-target agents. These methods have shown promising potential in facilitating drug discovery directed at selective multiple targets. [ABSTRACT FROM AUTHOR]

Positive, sigmoidal cooperativity is known to occur to a monomeric single-site enzyme with slow conformational fluctuations in its unbound (E) states when the enzyme undergoes steady-state catalytic turnover (mnemonic enzymes, hysteretic enzyme). We show that positive cooperativity occurs even when the E state is a single thermodynamic state, provided that the fluctuation amplitude of the state is sufficiently greater than that of the enzyme−substrate complex ES and the fluctuation times being comparable. This can occur even without mean structural change between E and ES. Slow conformational fluctuations are widely observed in enzymes. Our result suggests that enzymes with substrate association that reduces conformational fluctuations while maintaining fluctuation temporality can exhibit sigmoidal binding inside of living cells. Implications of this result on drug−target interactions are discussed. [ABSTRACT FROM AUTHOR]

Background and objective: COPD is a complex polygenic disease in which gene–environment interactions are very important. The gene encoding microsomal epoxide hydrolase (EPHX1) is one of several candidate loci for COPD pathogenesis and is highly polymorphic. Based χ on the polymorphisms of EPHX1 gene (tyrosine/histidine 113, histidine/arginine 139), the population can be classified into four groups of putative EPHX1 phenotypes (fast, normal, slow and very slow). A number of studies have investigated the association between the genotypes and phenotypes of EPHX1 and COPD susceptibility in different populations, with inconsistent results. A systematic review and meta-analysis of the published data was performed to gain a clearer understanding of this association. Methods: The MEDLINE database was searched for case–control studies published from 1966 to August 2007. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Results: Sixteen eligible studies, comprising 1847 patients with COPD and 2455 controls, were included in the meta-analysis. The pooled result showed that the EPHX1 113 mutant homozygote was significantly associated with an increased risk of COPD (OR 1.59, 95% CI: 1.14–2.21). Subgroup analysis supported the result in the Asian population, but not in the Caucasian population. When the analysis was limited to only the larger-sample-size studies, studies in which controls were in Hardy–Weinberg equilibrium and studies in which controls were smokers/ex-smokers, the pooled results supported the conclusion. The EPHX1 139 heterozygote protected against the development of COPD in the Asian population, but not in the Caucasian population. The other gene types of EPHX1 113 and EPHX1 139 were not associated with an increased risk of COPD. The slow activity phenotype of EPHX1 was associated with an increased risk of COPD. The fast activity phenotype of EPHX1 was a protective factor for developing COPD in the Asian population, but not in the Caucasian population. However, the very slow activity phenotype of EPHX1 was a risk for developing COPD in the Caucasian population, but not in the Asian population. Conclusions: The polymorphisms of EPHX1 113 and EPHX1 139 are genetic contributors to COPD susceptibility in Asian populations. The phenotypes of EPHX1 were contributors to overall COPD susceptibility. [ABSTRACT FROM AUTHOR]

CD8+CD122+ regulatory T cells (CD8+CD122+ Treg) are naturally occurring Treg that effectively suppress the proliferation and IFN-γ production of both CD8+ and CD4+ target cells. This study investigated the molecular mechanisms of the recognition of target cells by CD8+CD122+ Treg using an in vitro culture system that reconstitutes the regulatory action of these cells. Naive CD8+CD122+ Treg co-cultured with pre-activated T cells became active Treg that produced IL-10 and suppressed IFN-γ production from the target T cells. CD8+CD122+ Treg effectively suppressed the IFN-γ production of the target cells of syngeneic mouse strains but not of allogeneic mouse strains with incompatible MHC. By using MHC-congeneic mouse strains, MHC-restricted suppression by CD8+CD122+ Treg was further confirmed. The blockade of cell surface molecules either on the Treg or on the target cells by specific blocking antibodies indicated that H-2K, H-2D, αβTCR and CD8 were involved in the regulatory action but I-A and Qa-1 were not. These results indicate that CD8+CD122+ Treg recognize already-activated T cells via the interaction of conventional MHC class I–αβTCR and become active regulatory cells that produce IL-10 and suppress the target cells. [ABSTRACT FROM PUBLISHER]

CD8+CD122+ regulatory T cells are a newly identified, naturally occurring type of regulatory T cell that produce interleukin-10 (IL-10) and effectively suppress interferon-γ (IFN-γ) production from both CD8+ and CD4+ target cells. Molecular mechanisms responsible for the recognition of target cells by CD8+CD122+ regulatory T cells were investigated in this study by using an in vitro culture system that reconstitutes the regulatory action of these cells. CD8+CD122+ regulatory T cells did not produce IL-10 and did not suppress the IFN-γ production of allogeneic target T cells when they were stimulated by immobilized anti-CD3 antibody alone, but they clearly produced IL-10 and suppressed the IFN-γ production of target cells when stimulated by anti-CD3 plus anti-CD28-coated beads. IFN-γ production by major histocompatibility complex-class I-deficient T cells was also suppressed by CD8+CD122+ regulatory T cells stimulated with anti-CD3 plus anti-CD28 antibody but was not suppressed by cells stimulated by anti-CD3 alone. Experiments examining the blockade of cell surface molecules expressed on either the regulatory cells or the target cells by adding specific neutralizing antibodies in the culture indicated that CD80, CD86, and CD28 molecules were involved in the regulatory action, but cytotoxic T lymphocyte antigen-4, inducible costimulatory molecule (ICOS) and programmed death-1 (PD-1) molecules were not. Finally, CD8+CD122+ cells isolated from CD28-knockout (CD28−/−) mice showed no regulatory activity. These results indicate that CD8+CD122+ regulatory T cells recognize target T cells via the interaction of CD80/CD86–CD28 molecules to become active regulatory cells that produce suppressive factors such as IL-10. [ABSTRACT FROM AUTHOR]

TFEB-altered RCC is a rare entity whose therapeutic implications and long-term survival remain unclear, especially for metastatic cases. In this study, we reported the clinicopathologic and radiological features of eighteen novel TFEB-altered RCC cases and found that TFEB-altered RCC exhibited mixed morphological and radiological characteristics. For metastatic TFEB-altered RCC, immunotherapy-based drug combinations could be a promising treatment strategy. Introduction: TFEB-altered renal cell carcinoma (RCC) is a rare entity characterized by the rearrangement of the TFEB gene or TFEB amplified. The therapeutic implications and long-term survival of TFEB-altered RCC remain unclear, especially for metastatic cases. Materials and Methods: The current study initially enrolled 7604 consecutive RCC patients at our center and a total of 248 patients were selected for FISH and immunohistochemistry (IHC) analysis. Eventually, eighteen TFEB-altered RCC patients were identified. We then reported the clinical, morphological, IHC, and radiological features of these cases. Results: The median age at initial diagnosis was 45 years, ranging from 18 years to 66 years. The majority of the TFEB-altered RCC patients were male (61.1%), with localized disease (T1-2N0M0, 77.8%). The median split TFEB fluorescent signal was 24%, ranging from 15%-80%. The morphological characteristics of TFEB-altered RCC were variable, with acinar, papillary, solid, or nest patterns. IHC and magnetic resonance imaging features of TFEB-altered RCC were nonspecific. Nine patients with localized disease received partial nephrectomy and five patients with localized disease received radical nephrectomy. During the median follow-up of 67 months, no signs of recurrence or metastasis were found in these patients. Two patients had distant metastasis and received axitinib plus PD-1 immunotherapy. One of them died at 40-month follow-up and another still alive at 88-month follow-up. Conclusion: TFEB-altered RCC is an extremely rare variant, exhibited mixed morphological characteristics. The radiological feature lack specificity, resembling clear cell RCC or papillary RCC. Genetic analyses including FISH analysis is crucial in the diagnosis of TFEB-altered RCC. For localized TFEB-altered RCC, both radical nephrectomy and partial nephrectomy conferred satisfactory prognosis. For metastatic TFEB-altered RCC, immunotherapy-based drug combinations could be a promising treatment strategy. [ABSTRACT FROM AUTHOR]

Graphene decorated nanomaterials and nanostructures can potentially be used in military and medical science applications. In this article, we study the optical properties of a graphene wrapping silica core–shell spherical nanoparticle under illumination of external light by using the Mie theory. We find that the nanoparticle can exhibit surface plasmon resonance (SPR) that can be broadly tuned from mid infrared to near infrared via simply changing the geometric parameters. A simplified equivalent dielectric permittivity model is developed to better understand the physics of SPR, and the calculation results agree well qualitatively with the rigorous Mie theory. Both calculations suggest that a small radius of graphene wrapping nanoparticle with high Fermi level could move the SPR wavelength of graphene into the near infrared regime. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide and has a very poor prognosis. Its occurrence has been on the increase in recent years. Surgical resection and liver transplantation are the primary methods of treatment for HCC patients, but can only be applied to 15% of patients. The median survival time of unresectable or metastasizing HCC patients is only a few months. Existing systemic treatment methods are not effective for advanced HCC patients and a new method of treatment is needed for these patients. It has been established that the HCC occurs in multiple stages, however, the pathogenesis at a molecular level is not clear and many key factors are yet to be determined. In the past 30 years, it has become evident that the Ras/Raf/MEK/extracellular signal-regulated k inase (ERK) signaling pathway plays a significant role in the occurrence and development of HCC. This review focused on the association between the Ras/Raf/MEK/ERK signaling pathway and HCC. [ABSTRACT FROM AUTHOR]

We report a 15-year-old male patient with recurrent epileptic seizures for 12 years. Oral multiple drugs do not work well to his condition. MRI FLAIR scans revealed focal cortical dysplasia type II in the right parietal lobe. The diagnosis of the patient was drug-refractory epilepsy, FCD-related secondary epilepsy. According to the shape of the FCD lesion, electrodes were implanted in a tapered pattern along the bottom of the sulcus to completely destroy the focus. Magnetic resonance imaging at 6 months after surgery revealed that the FCD at the sulcus bottom was completely destroyed. After 26 months of follow-up, the patient had undergone no epileptic seizures, reaching Engel class I. For FCD that are located deep in the brain and adjacent to functional areas, craniotomy has a high risk. And stereoelectroencephalography-guided radiofrequency thermocoagulation may be a preferred treatment. [ABSTRACT FROM AUTHOR]

We identified CD8+CD122+ regulatory T cells (Tregs) and demonstrated their importance in the maintenance of immune homeostasis and in the recovery from experimental autoimmune encephalomyelitis. In this paper, we show that CD8+CD122+ Tregs effectively prevent and cure colitis in a mouse model. In our experiments, colitis was induced in lymphocyte-deficient RAG-2-/- mice by transferring CD4+CD45RBhigh cells that were excluded with CD4+ Tregs. Cotransfer of CD8+CD122+ cells clearly suppressed the development of colitis, and this suppressive effect was similar to that of CD4+CD45RBlow cells that were mostly CD4+ Tregs. CD8+CD122+ cells obtained from IL-10-/- mice were unable to suppress colitis, indicating that IL-10 is an important effect-transmitting factor in the suppression of colitis. CD8+CD122+ cells showed a suppressive effect when they were transferred 4 wk after CD4+CD45RBhigh cells, indicating the therapeutic potential of CD8+CD122+ cells. A mixture of CD8+CD122+ cells and CD4+CD45RBlow cells was far more effective than single Tregs, indicating the synergistic effect of these Tregs. These overall findings demonstrate the potential role of CD8+ Tregs, and possibly together with CD4+ Tregs, in the medical care of inflammatory bowel disease patients. [ABSTRACT FROM AUTHOR]

PRMT5 plays important roles in diverse cellular processes and is upregulated in several human malignancies. Besides, PRMT5 has been validated as an anticancer target in mantle cell lymphoma. In this study, we found a potent and selective PRMT5 inhibitor by performing structure-based virtual screening and hit optimization. The identified compound 17 (IC50 = 0.33 μM) exhibited a broad selectivity against a panel of other methyltransferases. The direct binding of 17 to PRMT5 was validated by surface plasmon resonance experiments, with a Kd of 0.987 μM. Kinetic experiments indicated that 17 was a SAM competitive inhibitor other than the substrate. In addition, 17 showed selective antiproliferative effects against MV4-11 cells, and further studies indicated that the mechanism of cellular antitumor activity was due to the inhibition of PRMT5 mediated SmD3 methylation. 17 may represent a promising lead compound to understand more about PRMT5 and potentially assist the development of treatments for leukemia indications. [ABSTRACT FROM AUTHOR]

Impairment of amyloid-ß (Aß) clearance leads to Aß accumulation in the brain during the development of Alzheimer's disease (AD). Strategies that can restore or improve the clearance function hold great promise in delaying or preventing the onset of AD. Here, we show that n-3 polyunsaturated fatty acids (PUFAs), by use of fat-1 transgenic mice and oral administration of fish oil, significantly promote interstitial Aß clearance from the brain and resist Aß injury. Such beneficial effects were abolished in Aqp4-knockout mice, suggesting that the AQP4-dependent glymphatic system is actively involved in the promoting the effects of n-3 PUFAs on the clearance of extracellular Aß. Imaging on clarified brain tissues clearly displayed that n-3 PUFAs markedly inhibit the activation of astrocytes and protect the AQP4 polarization in the affected brain region after Aß injection. The results of the present study prove a novel mechanism by which n-3 PUFAs exert protective roles in reducing Aß accumulation via mediating the glymphatic system function. [ABSTRACT FROM AUTHOR]

Liver injury is a major hindrance to the treatment of tuberculosis (TB) patients due to the primary side effects associated with anti-TB drugs. Several investigations have identified sensitive biomarkers for the early diagnosis of anti-TB drug-induced liver injury (ADLI), including the use of microRNAs (miRNAs/miRs). However, the association between miR-122/155 and ADLI remains unknown. Thus, the present study used reverse transcription-quantitative polymerase chain reaction to observe changes in tissue miR-122/155 expression levels during the course of liver injury in mice. Liver injury was induced by the administration of isoniazid (INH), a first-line anti-TB drug. miR-122/155 expression levels were quantified at seven time points throughout 1 day (0.25, 0.75, 1.5, 6, 12, 18 and 24 h) based on the pharmacokinetics of INH in mice. Notably, over the timecourse of INH-induced liver injury, the tissue miR-122 expression level significantly decreased at 0.25 h, which is the peak concentration time of INH, compared with the control group (P<0.05). The change was more rapid than that of the serum aminotransferase and miR-155, which were significantly increased at 0.75 h. In addition, the pathological score correlated with the ratio of miR-122/miR-155 (r=-0.779; P<0.01). In conclusion, the miR-122/155 ratio may be utilized as a sensitive biomarker for ADLI, which could contribute to the early diagnosis of patients following anti-TB treatment. [ABSTRACT FROM AUTHOR]

Voltage source converter (VSC)-based high voltage direct current (VSC-HVDC) interconnectors can realize accurate and fast control of power transmission among AC networks, and provide emergency power support for AC networks. VSC-HVDC interconnectors bring exclusive fault characteristics to AC networks, thus influencing the performance of traditional protections. Since fault characteristics are related to the control schemes of interconnectors, a fault ride-through (FRT) strategy which is applicable to the interconnector operating characteristic of working in four quadrants and capable of eliminating negative-sequence currents under unbalanced fault conditions is proposed first. Then, the additional terms of measured impedances of distance relays caused by fault resistances are derived using a symmetrical component method. Theoretical analysis shows the output currents of interconnectors are controllable after faults, which may cause malfunctions in distance protections installed on lines emanating from interconnectors under the effect of fault resistances. Pilot protection is also inapplicable to lines emanating from interconnectors. Furthermore, a novel pilot protection principle based on the ratio between phase currents and the ratio between negative-sequence currents flowing through both sides is proposed for lines emanating from the interconnectors whose control scheme aims at eliminating negative-sequence currents. The validity of theoretical analysis and the protection principle is verified by PSCAD/EMTDC simulations. [ABSTRACT FROM AUTHOR]

We experimentally measure the angular distribution of plasma luminescence emission during the filamentation of linearly polarized femtosecond laser pulses. It is found that the luminescence from N2 shares the same intensity in all directions, while that from N+2 is more intense in the direction parallel to that of the laser polarization. The isotropic emission behavior of luminescence from N2 illustrates that the formation of excited N2(C3Πu+) does not result from the dissociative recombination; on the other hand, the linear increase of the strength of 337 nm signal with pressure indicates that the collision plays a negligible role, excluding the collision assisted intersystem crossing scheme. However, the intersystem crossing does not rely on the collision, making it a possible scheme. This study will be helpful to the understanding of mechanism of plasma luminescence emission during femtosecond filamentation. [ABSTRACT FROM AUTHOR]

Two types of 500 MPa anti-seismic rebars were produced by V-Nb microalloyed combined with controlled rolling and cooling technology, the strengthening and toughening mechanism of which were investigated. The complex phase microstructures of specimens consist of ferrite, pearlite and bainite ( 6 -1 0 %). Furthermore, a large number of V(C,N) and Nb(C,N) precipitates with size of 5 - 30 nm formed in the ferrite matrix, grain boundaries and on dislocation lines, promoting the precipitation strengthening and inhibiting grain coarsening to controlled cooling microstructure. The mechanical performance of the steels was improved by solution and grain refinement strengthening, precipitation and microstructure strengthening. And the best strengthening effect was obtained by grain refinement, which increased the yield strength more than 35% strength increment contribution ratio to yield strength. Moreover, about 16.5% microstructure strengthening increment was obtained due to bainite formation. The plasticity and low-temperature toughness enhancement were mainly attributed to ferrite grain refinement improvement. [ABSTRACT FROM AUTHOR]

Due to extensive bioprospecting efforts of the past and technology factors, there have been questions about drug discovery prospect from untapped species. We analyzed recent trends of approved drugs derived from previously untapped species, which show no sign of untapped drug-productive species being near extinction and suggest high probability of deriving new drugs from new species in existing drug-productive species families and clusters. Case histories of recently approved drugs reveal useful strategies for deriving new drugs from the scaffolds and pharmacophores of the natural product leads of these untapped species. New technologies such as cryptic gene-cluster exploration may generate novel natural products with highly anticipated potential impact on drug discovery. [ABSTRACT FROM AUTHOR]

A series of direct smelting reduction experiment has been carried out with high phosphorous iron ore of the different bases by thermogravimetric analyzer. The derivative thermogravimetric (DTG) data have been obtained from the experiments. One- step forward local weighted linear (LWL) method , one of the most suitable ways of predicting chaotic time-series methods which focus on the errors, is used to predict DTG. In the meanwhile, empirical mode decomposition-auto regressive (EMD-AR), a data mining technique in signal processing, is also used to predict DTG. The results show that (1) EMD-AR(4) is the most appropriate and its error is smaller than the former; (2) root mean square error (RMSE) has decreased about two-thirds; (3) standardized root mean square error (NMSE) has decreased in an order of magnitude. Finally in this paper, EMD- AR method has been improved by golden section weighting; its error would be smaller than before. Therefore, the improved EMD-AR model is a promising alternative for apparent reaction rate (DTG). The analytical results have been an important reference in the field of industrial control. [ABSTRACT FROM AUTHOR]

Many drugs are nature derived. Low drug productivity has renewed interest in natural products as drug-discovery sources. Nature-derived drugs are composed of dozens of molecular scaffolds generated by specific secondary-metabolite gene clusters in selected species. It can be hypothesized that drug-like structures probably are distributed in selective groups of species. We compared the species origins of 939 approved and 369 clinical-trial drugs with those of 119 preclinical drugs and 19,721 bioactive natural products. In contrast to the scattered distribution of bioactive natural products, these drugs are clustered into 144 of the 6,763 known species families in nature, with 80% of the approved drugs and 67% of the clinical-trial drugs concentrated in 17 and 30 drug-prolific families, respectively. Four lines of evidence from historical drug data, 13,548 marine natural products, 767 medicinal plants, and 19,721 bioactive natural products suggest that drugs are derived mostly from preexisting drug-productive families. Drug-productive clusters expand slowly by conventional technologies. The lack of drugs outside drug-productive families is not necessarily the result of under-exploration or late exploration by conventional technologies. New technologies that explore cryptic gene clusters, pathways, interspecies crosstalk, and high-throughput fermentation enable the discovery of novel natural products. The potential impact of these technologies on drug productivity and on the distribution patterns of drug-productive families is yet to be revealed. [ABSTRACT FROM AUTHOR]

Abstract  The efficacy of neurolytic coeliac plexus block (NCPB) guided by computerized tomography (CT) was compared with pharmacological therapy in the treatment of pain due to pancreatic cancer. The study involved 56 patients who were placed randomly in either a NCPB group and pharmacological therapy group. At day 1, 7, and 14, the visual analogue scale (VAS) pain scores of the NCPB group were significantly lower than those of the pharmacological therapy group (P [ABSTRACT FROM AUTHOR]

Monosized strontium titanate (SrTiO3) particles with tailored morphologies have been successfully synthesized using ultrasound irradiation. Characterization techniques such as X-ray powder diffraction analysis, scanning electron microscopy, energy-dispersive analysis of X-rays, and laser particle size analysis were used to investigate the products. The results showed that all the as-prepared powders have a cubic SrTiO3 structure. Reaction conditions such as reactant concentrations, sonication time, and sonication power were found to have important effects on the morphology of SrTiO3 particles. [ABSTRACT FROM AUTHOR]

We observed postnecrotic tissue remodeling to examine vascularization in adult rat livers. Livers, bone marrow, and peripheral blood from rats at 24 h to 14 days after an injection of dimethylnitrosamine (DMN) were examined by light microscopic, immunohistochemical, and ultrastructural methods. Numerous ED-1 (a marker for rat monocytes/macrophages)-positive round mononuclear cells infiltrated in the necrotic areas at 36 h after DMN treatment. On day 5, when necrotic tissues were removed, some of the cells were transformed from round to spindle in shape. On day 7, these cells were contacted with residual reticulin fibers and became positive for SE-1, a marker of hepatic sinusoidal endothelial cells and Tie-1, an endothelial cell-specific surface receptor, associated with frequent occurrence of ED-1/SE-1 and ED-1/Tie-1 double-positive spindle cells. Ultrastructurally, the spindle cells simultaneously showed phagocytosis and endothelial cell-like morphology. With time necrotic areas diminished, and on day 14, the necrotic tissues were almost replaced by regenerated liver tissues and thin bundles of central-to-central bridging fibrosis. Bone marrow from 12 h to day 2 showed an increase of BrdU-positive mononuclear cells. Some of them were positive for ED-1. The BrdU-labeled and ED-1-positive cells appeared as early as 12 h after DMN injection and reached a peak in number at 36 h. They were similar in structure to ED-1-positive cells in necrotic liver tissues. These findings suggest that round mononuclear ED-1-positive cells proliferate first in bone marrow after DMN treatment, reach necrotic areas of the liver through the circulation, and differentiate to sinusoidal endothelial cells. Namely, hepatic sinusoids in DMN-induced necrotic areas may partly be reorganized possibly by vasculogenesis. [ABSTRACT FROM AUTHOR]

A self-powered graphene-based photodetector with high performance is particularly useful for device miniaturization and to save energy. Here, we report a graphene/silicon carbide (SiC)-based self-powered ultraviolet photodetector that exhibits a current responsivity of 7.4 mA/W with a response frequency of over a megahertz under 325-nm laser irradiation. The built-in photovoltage of the photodetector is about four orders of magnitude higher than previously reported results for similar devices. These favorable properties are ascribed to the ingenious device design using the combined advantages of graphene and SiC, two terminal electrodes, and asymmetric light irradiation on one of the electrodes. Importantly, the photon energy is larger than the band gap of SiC. This self-powered photodetector is compatible with modern semiconductor technology and shows potential for applications in ultraviolet imaging and graphene-based integrated circuits. [ABSTRACT FROM AUTHOR]

The article focuses on a study which analyzed if community based integrated interventions have an effect on early prevention and management of chronic pulmonary disease (COPD), especially the annual rate of decline in forced expiratory volume in one second (FEV1). Study participants, aged 40-89 with COPD and without COPD, were randomly assigned to integrated intervention or usual care. The study found a significantly lower annual rate decline in FEV1 in the intervention community than the control community.