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Atmosphere aerosol nucleation contributes to climate change, air pollution, and human health, however the mechanisms are complex and elusive. Here the authors propose a general workflow based on deep neural network-based force field, paving the way towards fully ab initio simulation of atmospheric aerosol nucleation.

BackgroundSecondary hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disease of immune hyperactivation that arises in the context of infectious, inflammatory, or neoplastic triggers. The aim of this study was to establish a predictive model for the timely differential diagnosis of the original disease resulting in HLH by validating clinical and laboratory findings to further improve the efficacy of therapeutics for HLH.MethodsWe retrospectively enrolled 175 secondary HLH patients in this study, including 92 patients with hematologic disease and 83 patients with rheumatic disease. The medical records of all identified patients were retrospectively reviewed and used to generate the predictive model. We also developed an early risk score using multivariate analysis weighted points proportional to the β regression coefficient values and calculated its sensitivity and specificity for the diagnosis of the original disease resulting in HLH.ResultsThe multivariate logistic analysis revealed that lower levels of hemoglobin and platelets (PLT), lower levels of ferritin, splenomegaly and Epstein−Barr virus (EBV) positivity were associated with hematologic disease, but young age and female sex were associated with rheumatic disease. The risk factors for HLH secondary to rheumatic diseases were female sex [OR 4.434 (95% CI, 1.889-10.407), P =0.001], younger age [OR 6.773 (95% CI, 2.706-16.952), P

Rapidly finding low-energy structures on high-dimensional potential energy surfaces remains a challenging problem for cluster science. We present a fast optimization method for structure prediction named mirror-rotation searching, which is inspired by the idea of symmetry and conservation. Our search algorithm can quickly converge to the minima of energy valley by continuously performing mirror-rotation transformation on the cluster, and we introduce the term vaminima to describe these minima. For the selected Lennard-Jones cluster of size N≤150, convergence to a vaminima on average takes 413 relaxations, and finding fullerene C_{60} from a random initial structure is 49-fold faster than the traditional genetic algorithm. The approach is general and flexible and can greatly improve the search efficiency of unbiased global optimization algorithms and be applied to different kinds of problems, such as molecular structure search, crystal structure prediction, and protein folding.

Abstract Background Common and rare variants of guanosine triphosphate cyclohydrolase 1 (GCH1) gene may play important roles in Parkinson’s disease (PD). However, there is a lack of comprehensive analysis of GCH1 genotypes, especially in non-coding regions. The aim of this study was to explore the genetic characteristics of GCH1, including rare and common variants in coding and non-coding regions, in a large population of PD patients in Chinese mainland, as well as the phenotypic characteristics of GCH1 variant carriers. Methods In the first cohort of this case-control study, we performed whole-exome sequencing in 1555 patients with early-onset or familial PD and 2234 healthy controls; then in the second cohort, whole-genome sequencing was performed in sporadic late-onset PD samples (1962 patients), as well as 1279 controls. Variants at target GCH1 regions were extracted, and then genetic and detailed phenotypic data were analyzed using regression models and the sequence kernel association test. We also performed a meta-analysis to correlate deleterious GCH1 variants with age at onset (AAO) in PD patients. Results For coding variants, we identified a significant burden of GCH1 deleterious variants in early-onset or familial PD cases compared to controls (1.2% vs 0.1%, P

Abstract A low‐profile metasurface antenna with circularly polarized radiation and tailored anisotropic reflection is proposed in this letter. The metasurface antenna composed of excitation structure (microstrip line with coupling slot) and a metasurface layer. The metasurface functions for two goals, generating circularly polarized wave for radiation and tailoring reflection phase for scattering, respectively. The overall structure of the metasurface antenna is compact with a dimension of 0.67λ × 0.67λ × 0.05λ at 5 GHz. Numerical and measured results confirm that the metasurface antenna exhibits 11.1% −10 dB S11 bandwidth from 4.68 to 5.23 GHz, 10.8% 3 dB axial ratio bandwidth from 4.782 to 5.37 GHz and a maximum gain of 6.83 dBic. Besides, the metasurface antenna achieves anti‐phase reflection under orthogonal polarized incident waves at around 5 GHz. To demonstrate a potential application, 16 identical metasurface antennas are put in a 4 × 4 array. The metasurface antenna array achieves directive circularly polarized radiation with a maximum gain of 15 dBic. On the other hand, when under normal illumination, the scattering field of metasurface antenna array is redistributed due to phase cancelation, so that the backward radar cross section of the array is significantly reduced, which is applicable for military platform.

Starch is the most important component in endosperm of sorghum grain. Usually, two types of starch are present: amylose (AM) and amylopectin (AP). The levels of AM and AP contents play a significant role in the appearance, structure, and quality of sorghum grains and in marketing applications. In the present study, a panel of 634 sorghum (Sorghum bicolor (L.) Moench) accessions were evaluated for starch, AM, and AP contents of grain, which included a mini core collection of 242 accessions from the International Crops Research Institute for the Semi-Arid Tropics (ICRISAT) in India, and 252 landraces and 140 cultivars from China. The average starch content was 67.64% and the average AM and AP contents were 20.19 and 79.81%, respectively. We developed a total of 260 000 high-confidence single nucleotide polymorphism (SNP) markers in the panel of 634 accessions of S. bicolor using specific locus amplified fragment sequencing (SLAF-seq). We performed genome-wide association studies (GWAS) of starch, AM, and AM/AP of grain and SNP markers based on a mixed linear model (MLM). In total, 70 significant association signals were detected for starch, AM, and AM/AP ratio of grain with P

Bone-related malignancies, such as osteosarcoma, Ewing’s sarcoma, multiple myeloma, and cancer bone metastases have similar histological context, but they are distinct in origin and biological behavior. We hypothesize that a distinct immune infiltrative microenvironment exists in these four most common malignant bone-associated tumors and can be used for tumor diagnosis and patient prognosis. After sample cleaning, data integration, and batch effect removal, we used 22 publicly available datasets to draw out the tumor immune microenvironment using the ssGSEA algorithm. The diagnostic model was developed using the random forest. Further statistical analysis of the immune microenvironment and clinical data of patients with osteosarcoma and Ewing’s sarcoma was carried out. The results suggested significant differences in the microenvironment of bone-related tumors, and the diagnostic accuracy of the model was higher than 97%. Also, high infiltration of multiple immune cells in Ewing’s sarcoma was suggestive of poor patient prognosis. Meanwhile, increased infiltration of macrophages and B cells suggested a better prognosis for patients with osteosarcoma, and effector memory CD8 T cells and type 2 T helper cells correlated with patients’ chemotherapy responsiveness and tumor metastasis. Our study revealed that the random forest diagnostic model based on immune infiltration can accurately perform the differential diagnosis of bone-related malignancies. The immune microenvironment of osteosarcoma and Ewing’s sarcoma has an important impact on patient prognosis. Suppressing the highly inflammatory environment of Ewing’s sarcoma and promoting macrophage and B cell infiltration may have good potential to be a novel adjuvant treatment option for osteosarcoma and Ewing’s sarcoma.

This paper incorporates the Bingham rheology model with the Navier–Stokes solver to simulate the tsunamis excited by a slump-type landslide. The slump is modeled as the Bingham material, in which the rheological properties changing from the un-yield phase to yield phase is taken into account. The volume of fluid method is used to track the interfaces between three materials: air, water, and slump. The developed model is validated by the laboratory data of the benchmark landslide tsunami problem. A series of rheological properties analyses is performed to identify the parameter sensitivity to the tsunami generation. The results show that the yield stress plays a more important role than the yield viscosity in terms of the slump kinematics and tsunami generation. Moreover, the scale effect is investigated under the criterion of Froude number similarity and Bingham number similarity. With the same Froude number and Bingham number, the result from the laboratory scale can be applied to the field scale. If the slump material collected in the field is used in the laboratory experiments, only the result of the maximum wave height can be used, and significant errors in slump shape and moving speed are expected.

This paper incorperates Bingham and bi-viscosity rheology models with the Navier–Stokes solver to simulate the dynamics and kinematics processes of slumps for tsunami generation. The rheology models are integrated into a computational fluid dynamics code, Splash3D, to solve the incompressible Navier–Stokes equations with volume of fluid surface tracking algorithm. The change between un-yield and yield phases of the slide material is controlled by the yield stress and yield strain rate in Bingham and bi-viscosity models, respectively. The integrated model is carefully validated by the theoretical results and laboratory data with good agreements. This validated model is then used to simulate the benchmark problem of the failure of the gypsum tailings dam in East Texas in 1966. The accuracy of predicted flood distances simulated by both models is about 73% of the observation data. To improve the prediction, a fixed large viscosity is introduced to describe the un-yield behavior of tailings material. The yield strain rate is obtained by comparing the simulated inundation boundary to the field data. This modified bi-viscosity model improves not only the accuracy of the spreading distance to about 97% but also the accuracy of the spreading width. The un-yield region in the modified bi-viscosity model is sturdier than that described in the Bingham model. However, once the tailing material yields, the material returns to the Bingham property. This model can be used to simulate landslide tsunamis.

Sheep is an important livestock in the world providing meat, milk and wool for human beings. With increasing human population, the worldwide needs of production of sheep have elevated. To meet the needs, the assistant reproductive technology including ovine in vitro embryo production (ovine IVP) is urgently required to enhance the effective production of sheep in the world. To learn the status of ovine IVP, we collected some publications related to ovine IVP through PubMed and analyzed the progress in ovine IVP made in the last five years (2012–2017). We made comparisons of these data and found that the recent advances in ovine IVP has been made slowly comparable to that of ovine IVP two decades ago. Therefore, we suggested two strategies or approaches to tackle the main problems in ovine IVP and expect that the efficiency of ovine IVP could be improved significantly when the approaches would be implemented. Keywords: Embryos, IVF, IVM, IVP, Oocyte, Sheep

Objective: To summarize the clinical presentation, pathogenesis, neuroimaging, treatment, and outcome of stroke-like migraine attacks after radiation therapy (SMART) syndrome, and to propose diagnostic criteria for this disorder. Data Sources: We searched the PubMed database for articles in English published from 1995 to 2015 using the terms of "stroke-like AND migraine AND radiation." Reference lists of the identified articles and reviews were used to retrieve additional articles. Study Selection: Data and articles related to late-onset effects of cerebral radiation were selected and reviewed. Results: SMART is a rare condition that involves complex migraines with focal neurologic deficits following cranial irradiation for central nervous system malignancies. The recovery, which ranges from hours to days to weeks, can be partial or complete. We propose the following diagnostic criteria for SMART: (1) Remote history of therapeutic external beam cranial irradiation for malignancy; (2) prolonged, reversible clinical manifestations mostly years after irradiation, which may include migraine, seizures, hemiparesis, hemisensory deficits, visuospatial defect, aphasia, confusion and so on; (3) reversible, transient, unilateral cortical gadolinium enhancement correlative abnormal T2 and fluid-attenuated inversion recovery signal of the affected cerebral region; (4) eventual complete or partial recovery, the length of duration of recovery ranging from hours to days to weeks; (5) no evidence of residual or recurrent tumor; (6) not attributable to another disease. To date, no specific treatment has been identified for this syndrome. Conclusions: SMART is an extremely rare delayed complication of brain irradiation. However, improvements in cancer survival rates have resulted in a rise in its frequency. Hence, awareness and recognition of the syndrome is important to make a rapid diagnosis and avoid aggressive interventions such as brain biopsy and cerebral angiography.

Objective: To investigate the influence of edaravone on the expression of growth arrest and DNA damage-inducible protein 34 (GADD34). Methods: A total of 108 healthy male Sprague-Dawley rats were randomly divided into sham operation group, model group and edaravone group (36 cases for each group). Transient focal cerebral ischemia was induced by middle cerebral artery occlusion for 2 h followed by reperfusion in Sprague-Dawley rats. Then, GADD34 expression was measured with immunohistochemistry at different time-points after reperfusion in the peri-infarct regions of all rats. Results: The GADD34 expression was detected in the peri-infarct regions of rats 1 h after reperfusion, which reached its peak 24 h after reperfusion. And edaravone could significantly down-regulate the GADD34 expression. Conclusions: Edaravon could down-regulate GADD34 expression, which suggests that edaravone may exert an important function in inhibiting endoplasmic reticulum stress reaction by scavenging free radicals in the upper stream.

Radiation is a widely used therapeutic method for treating breast cancer. N-dihydrogalactochitosan (GC), a biocompatible immunostimulant, is known to enhance the effects of various treatment modalities in different tumor types. However, whether GC can enhance the radiosensitivity of cancer cells remains to be explored. In this study, triple-negative murine 4T1 breast cancer cells transduced with multi-reporter genes were implanted in immunocompetent Balb/C mice to track, dissect, and identify liver-metastatic 4T1 cells. These cells expressed cancer stem cell (CSC) -related characteristics, including the ability to form spheroids, the expression of the CD44 marker, and the increase of protein stability. We then ex vivo investigated the potential effect of GC on the radiosensitivity of the liver-metastatic 4T1 breast cancer cells and compared the results to those of parental 4T1 cells subjected to the same treatment. The cells were irradiated with increased doses of X-rays with or without GC treatment. Colony formation assays were then performed to determine the survival fractions and radiosensitivity of these cells. We found that GC preferably increased the radiosensitivity of liver-metastatic 4T1 breast cancer cells rather than that of the parental cells. Additionally, the single-cell DNA electrophoresis assay (SCDEA) and γ-H2AX foci assay were performed to assess the level of double-stranded DNA breaks (DSBs). Compared to the parental cells, DNA damage was significantly increased in liver-metastatic 4T1 cells after they were treated with GC plus radiation. Further studies on apoptosis showed that this combination treatment increased the sub-G1 population of cells, but not caspase-3 cleavage, in liver-metastatic breast cancer cells. Taken together, the current data suggest that the synergistic effects of GC and irradiation might be used to enhance the efficacy of radiotherapy in treating metastatic tumors.

Ammonia and amines are important common trace atmospheric species that can enhance new particle formation (NPF) in the Earth's atmosphere. However, the synergistic effect of these two bases involving nucleation is still lacking. We studied the most stable geometric structures and thermodynamics of quaternary (NH3)(CH3NH2)(H2SO4)m(H2O)n (m = 1-3, n = 0-4) clusters at the PW91PW91/6-311++G(3df,3pd) level of theory for the first time. We find that the proton transfer from H2SO4 molecule to CH3NH2 molecule is easier than to NH3 molecule in the free or hydrated H2SO4-base clusters, and thus leads to the stability. The energetically favorable formation of the (NH3)(CH3NH2)(H2SO4)m(H2O)n (n = 0-4) clusters, by hydration or attachment of base or substitution of ammonia by methylamine at 298.15 K, indicate that ammonia and methylamine together could enhance the stabilization of small binary clusters. At low RH and an ambient temperature of 298.15 K, the concentration of total hydrated (NH3)(CH3NH2)(H2SO4)2 clusters could reach that of total hydrated (NH3)(H2SO4)2 clusters, which is the most stable ammonia-containing cluster. These results indicate that the synergistic effect of NH3 and CH3NH2 might be important in forming the initial cluster with sulfuric acid and subsequently growth process. In addition, the evaporation rates of (NH3)(CH3NH2)(H2SO4)(H2O), (NH3)(CH3NH2)(H2SO4)2 and (NH3)(CH3NH2)(H2SO4)3 clusters, three relative abundant clusters in (NH3)(CH3NH2)(H2SO4)m(H2O)n system, were calculated. We find the stability increases with the increasing number of H2SO4 molecules. [ABSTRACT FROM AUTHOR]

The core-shell oil absorption material (OAM) with fumed silica shell was achieved from Pickering polymerization. The modified fumed silica wall could well stabilize both Pickering emulsion and Pickering polymerization. The particle size of encapsulated OAMs decreased with the increasing concentration of fumed silica and remained unchanged when the concentration was more than 1 wt.%. This fumed silica shell had little effect on the oil absorption rate of OAM. The importance was that the shell reversed the surface property and improved the alkali resistance of OAM. We believe that our core-shell OAMs could reach the self-healing ability of the oil well cement. [ABSTRACT FROM AUTHOR]

Amino acids are recognized as important components of atmospheric aerosols, which impact on the Earth's climate directly and indirectly. However, much remains unknown about the initial events of nucleation. In this work, the interaction of alanine [NH2CH(CH3)COOH or Ala], one of the most abundant amino acids in the atmosphere, with sulfuric acid (SA) and water (W) has been investigated at the M06-2X/6-311++G(3df, 3pd) level of theory. We have studied thermodynamics of the hydrated (Ala)(SA) core system with up to four water molecules. We found that Ala, with one amino group and one carboxyl group, can interact with H2SO4 and H2O in two directions and that it has a high cluster stabilizing effect similar to that of ammonia, which is one of the key nucleation precursor. The corresponding Gibbs free energies of the (Ala)(SA)(W)n (n = 0-4) clusters formation at 298.15 K predicted that Ala can contribute to the stabilization of small binary clusters. Our results showed that the hydrate distribution is temperature-dependent and that a higher humidity and temperature can contribute to the formation of hydrated clusters. [ABSTRACT FROM AUTHOR]

Ditopic pillarene-based fluorescence enhancement material induced by [c2]daisy chain formation has been successfully fabricated. The highly fluorescent smart material exhibits great adaptivity and can act as a multi-responsive supramolecular sensor. [ABSTRACT FROM AUTHOR]

P bodies are cytoplasmic RNA granules containing the Dcp1-Dcp2 decapping enzymes where mRNA decay can occur. Here, we describe the characterization of P bodies in the fission yeast Schizosaccharomyces pombe. Most information on the property and function of P bodies stems from studies in the distantly related budding yeast Saccharomyces cerevisiae, and Edc3 was identified as a scaffold protein required for P-body assembly. However, we found that, unlike in S. cerevisiae, fission yeast Edc3 was dispensable for P-body formation. Pdc1, a novel partner of the fission yeast decapping enzyme, with a limited similarity to plant Edc4/Varicose that is required for the assembly of P bodies, was identified (tandem affinity purification--matrix-assisted laser desorption ionization tandem mass spectrometry [TAP-MALDI MS/MS]). Pdc1 interacts with Dcp2 through its C terminus and contains a coiled-coil region for self-interaction to mediate P-body formation. In line with the model that Pdc1 cross-bridges different proteins, additional interactions can be demonstrated with components such as Edc3 and Ste13. Although Pdc1 is not required for the interaction between Dcp1 and Dcp2, our data suggest that Pdc1 acts as a functional homologue of Edc4, a third component of the decapping enzymes that is thought to be absent from fungi. Together, these results highlight the diverse P-body protein compositions between different species and might help to provide insight into their evolutionary paths. [ABSTRACT FROM AUTHOR]

Background: Polypharmacy is common in outpatients and has been identified as a major risk factor for drug-drug interactions (DDIs), which are an important cause of adverse drug reactions. There has been a rapid increase in the number of elderly patients worldwide. However, there have been few studies quantifying the impact of both patient age and the number of concomitant drugs prescribed on the probability of potential DDIs per person in general outpatients. Objective: To assess the extent to which polypharmacy and aging are associated with potential DDIs in outpatients at a medical centre in Taiwan. Methods: The medications of 81 650 outpatients who visited a medical centre in Taiwan between January 2004 and March 2004 were retrospectively screened for potential DDIs using a computerized drug-interaction program. The main inclusion criteria were a minimum of two drug prescriptions and duration of use of 14 or more days. We also analysed the DDI pattern, which included severity, level of documentation and onset of potential DDIs, and assessed the impact of the number of drugs prescribed and of aging on the prevalence of potential DDIs per person. Results: The prevalence of potential DDIs was 25.6% (20 902 of 81 650). The mean±SD age of the 20902 patients with potential DDIs was 57.5±16.5 years, and 47.6% of these patients were male. The mean±SD number of prescribed drugs in patients with potential DDIs was 5.8 ±2.4, and 67.7% of these patients were prescribed more than four drugs. The majority (55.7%) of DDIs were of the C2 pattern (severity: moderate; documentation: probable). The prevalence of potential DDIs increased in a linear mode with increasing age (p<0.001) and with the number of drugs prescribed (p<0.001); furthermore, in addition to being independently associated with potential DDIs, these two factors interacted to increase the risk further. Conclusions: This study showed that approximately one-quarter of 81 650 outpatients who visited a medical centre in Taiwan over a period of 3 months in 2004 had potential DDIs. We observed independent increases in potential DDIs per person in association with aging and increasing number of prescribed drugs. Furthermore, a significant interaction between these two factors was observed: the effect of aging on the prevalence of potential DDIs increased as the number of prescribed drugs increased. Potential DDIs in outpatients can be reduced by minimizing the number of drugs prescribed following careful consideration of both their benefits and risks, particularly in the aging population. [ABSTRACT FROM AUTHOR]

Abstract  TagSNP selection, which aims to select a small subset of informative single nucleotide polymorphisms (SNPs) to represent the whole large SNP set, has played an important role in current genomic research. Not only can this cut down the cost of genotyping by filtering a large number of redundant SNPs, but also it can accelerate the study of genome-wide disease association. In this paper, we propose a new hybrid method called CMDStagger that combines the ideas of the clustering and the graph algorithm, to find the minimum set of tagSNPs. The proposed algorithm uses the information of the linkage disequilibrium association and the haplotype diversity to reduce the information loss in tagSNP selection, and has no limit of block partition. The approach is tested on eight benchmark datasets from Hapmap and chromosome 5q31. Experimental results show that the algorithm in this paper can reduce the selection time and obtain less tagSNPs with high prediction accuracy. It indicates that this method has better performance than previous ones. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown genetic variation is the basis of the genome-wide disease association research. However, due to the high cost on genotyping large number of single nucleotide polymorphisms (SNPs), it is essential to choose a small subset of informative SNPs (tagSNPs), which are able to capture most variation in a population, to represent the rest SNPs. Several methods have been proposed to find the minimum set of tagSNPs, but most of them still have some disadvantages such as information loss and block-partition limit. Results: This paper proposes a new hybrid method named CGTS which combines the ideas of the clustering and the graph algorithms to select tagSNPs on genotype data. This method aims to maximize the number of the discarding nontagSNPs in the given set. CGTS integrates the information of the LD association and the genotype diversity using the site graphs, discards redundant SNPs using the algorithm based on these graph structures. The clustering algorithm is used to reduce the running time of CGTS. The efficiency of the algorithm and quality of solutions are evaluated on biological data and the comparisons with three popular selecting methods are shown in the paper. Conclusion: Our theoretical analysis and experimental results show that our algorithm CGTS is not only more efficient than other methods but also can be get higher accuracy in tagSNP selection. [ABSTRACT FROM AUTHOR]

Arsenic and lead can induce genetic injuries and epigenetic signaling pathways in cultured mammalian cells. To test whether signaling pathways affect the extent of genetic injuries, we explored the impacts of extracellular signal-regulated kinase 1 and 2 (ERK) on nucleotide excision repair (NER), cytotoxicity, and genotoxicity following sodium arsenite [As(III)] and lead acetate [Pb(II)]. Sustained ERK activation was observed in human cells exposed to As(III) and Pb(II). As(III) inhibited the cellular NER synthesis capability; conversely, Pb(II) stimulated it. ERK activation contributed to the As(III)-induced NER inhibition and micronucleus formation. In contrast, this signal was required for inducing cellular NER activity and preventing mutagenesis following Pb(II). ERK activation by Pb(II) was dependent on protein kinase C (PKCα) that also exhibited anti-mutagenicity. Enforced expression of ERK signaling markedly elevated the cellular NER activity, which was suppressed by As(III). Nonetheless, ERK activation could counteract the cytotoxicity caused by these two metals. Together, the results indicate that pro-survival ERK signaling exhibits dual and opposing impacts on NER process following As(III) and Pb(II) exposures. The findings also suggest that ERK is an important epigenetic signaling in the determination of metal genotoxicity. [ABSTRACT FROM AUTHOR]

OBJECTIVE To characterize a paracrine effect of prostatic epithelial cells in the presence or absence of oestradiol on the differentiation and proliferation of prostatic stromal cells. MATERIALS AND METHODS Conditioned media (CM) collected from a prostatic epithelial cell line (BPH-1), which was pre-treated with different concentration of oestradiol, were added to cultures of primary prostatic stromal cells. The proliferation rates of stromal cells were determined using a tetrazolium assay. The mRNA level was analysed by real-time reverse transcription-polymerase chain reaction (RT-PCR), and the protein level of smooth muscle myosin heavy chain (SM-MHC), fibronectin and collagen IV were determined with Western blotting, enzyme- linked immunosorbent assay and radioimmunoassay, respectively. The expression of transforming growth factor β1 (TGFβ1) in the BPH-1 cell line was analysed. RESULTS The rate of proliferation of stromal cells increased when they were cultured with CM harvested from oestradiol-treated BPH-1 cells, but there was no remarkable change when they were cultured with CM from untreated cells. The level of smoothelin mRNA and SM-MHC protein increased after treatment with CM from BPH-1. The CM from BPH-1 with oestradiol stimulation was more effective in stimulating smoothelin mRNA and SM-MHC protein level. The protein level of collagen type IV, but not fibronectin, was up-regulated in the supernatants and cell extracts of CM-treated stromal cells. Oestradiol enhanced the expression and secretion of TGFβ1 in BPH-1 cells. TGFβ1-neutralizing antibody abrogated the effect of BPH-1 CM on the synthesis of collagen IV and SM-MHC in stromal cells. CONCLUSION These results suggest that oestradiol-stimulated proliferation and differentiation of prostatic stromal cells could be regulated by factors secreted from prostatic epithelial cells. [ABSTRACT FROM AUTHOR]

OBJECTIVE To separate smooth muscle cells (SMCs) from fibroblasts in cultured human prostatic stromal cells (PrSCs) by characterizing the SM22 promoter as a prostatic SMC-specific gene promoter, and to investigate its use for a promoter-based cell-sorting method, as SMCs are critical for stromal function and the pathological changes in the development of benign prostatic hyperplasia. MATERIALS AND METHODS Human PrSCs were cultured in SMC-selective medium or standard medium, respectively, to obtain typical cultures of SMCs and fibroblasts. SM22 promoter activity and specificity were analysed by luciferase reporter-gene assay. A dual-colour vector was constructed with the expression of the red fluorescent protein (RFP) under the control of the 1.4 kb SMC-specific SM22 promoter, and the expression of the green fluorescent protein (GFP) under cytomegalovirus promoter. Fluorescence-activated cell sorting (FACS) was used to isolate and enrich GFP+/RFP+ and GFP+/RFP– cells. Cell phenotype was confirmed by reverse transcription-polymerase chain reaction and immunofluorescence. RESULTS The 1.4 kb SM22 promoter activity was much higher in PrSCs cultured in SMC-selective medium. Immunofluorescence staining and merged fluorescence microscopy ensured that SM22 promoter-driven GFP positive cells were SMCs. After transfection of the dual-colour vector into PrSCs, GFP+/RFP+ cells (SMCs) and GFP+/RFP– cells (fibroblasts) were isolated by FACS. The phenotype of FACS-enriched SMCs and fibroblasts was confirmed. CONCLUSION These results indicate that the 1.4 kb SM22 promoter is specific for prostatic SMCs. This dual-colour vector could be a useful tool for separating living SMCs from fibroblasts using FACS. [ABSTRACT FROM AUTHOR]

We present results of the electro-optical effect in 90° twisted nematic cells of pristine and doped liquid crystals under an applied dc voltage. The doped cells were fabricated with a minute addition of either buckminsterfullerene C60 or multiwalled carbon nanotubes (CNTs). Investigated were the switching behaviors as well as the hystereses and time evolutions of both the optical transmittance and electrical capacitance of the display samples. It is shown that doping with nanotubes can effectively reduce the dc driving voltage and improve the switching behavior. [ABSTRACT FROM AUTHOR]

Assembly of the adenovirus capsid protein hexon depends on the assistance of the molecular chaperone L4-100K. However, the chaperone mechanisms remain unclear. In this study, we found that L4-100K was involved in the hexon translation process and could prevent hexon degradation by the proteasome in cotransfected human cells. Two nonadjacent domains, 84-133 and 656-697, at the N-terminal and C-terminal regions of human adenovirus type 5 L4-100K, respectively, were found to be crucial and cooperatively responsible for hexon trimer expression and assembly. These two chaperone-related domains were conserved in the sequence of L4-100K and in the function of hexon assembly across different adenovirus serotypes. Different degrees of cross-activity of hexon trimerization with different serotypes were detected in subgroups B, C, and D, which were proven to be controlled by the interaction between the C-terminal chaperone-related domain of L4-100K and hypervariable regions (HVR) of hexon. Additionally, HVR-chimeric hexon mutants were successfully assembled with the assistance of the 1- 697 mutant. Structural analysis of 656-697 by nuclear magnetic resonance and structural prediction of L4-100K using Robetta showed that the two conserved domains are mainly composed of a-helices and are located on the surface of the highly folded core region. Our research provides a more complete understanding of hexon assembly and guidance for the development of hexon-chimeric adenovirus vectors that will be safer, smarter, and more efficient. IMPORTANCE Adenovirus vectors have been widely used in clinical trials of vaccines and gene therapy, although some deficiencies remain. Chimeric modification of the hexon was expected to improve the potency of preexisting immune evasion and targeting, but in many cases, viral packaging is prevented by the inability of the chimeric hexon to assemble correctly. So far, few studies have examined the mechanisms of hexon trimer assembly. Here, we show how the chaperone protein L4-100K contributes to the assembly of the adenovirus capsid protein hexon, and these data will provide a guide for novel adenovirus vector design and development, as we desired. [ABSTRACT FROM AUTHOR]

The nuclear factor κB (NF-κB)/Rel family of transcription factors participates in a wide range of biological activities including inflammation, immunity, and apoptosis. NF-κB is kept inactive in the cytoplasm in unstimulated cells by virtue of the masking of its nuclear localization sequence by bound IκB protein. Cellular stimuli trigger the destruction of IκB proteins and the liberation of NF-κB to enter the nucleus and activate gene expression. A multisubunit IκB kinase complex (IKK) phosphorylates IκB proteins and mediates the activation of NF-κB by proinflammatory stimuli such as tumor necrosis factor α. Phosphorylation of IκB proteins triggers their polyubiquitination and their subsequent recognition and degradation by the proteasome. The IKK complex contains two catalytic subunits, IKKα and IKKβ, and a noncatalytic subunit, NF-κB essential modifier/IKKγ. IKK activation depends upon the phosphorylation of residues in the activation loop of IKKβ and the subsequent activation of IKKβ kinase activity. However, the events contributing to IKKβ phosphorylation are not well understood. Here, we present evidence that the activation of IKKβ depends on its ability to form homotypic interactions and to transautophosphorylate. We find that an intact leucine zipper in IKKβ is necessary for homotypic interactions, kinase activation, and phosphorylation on its activation loop. Enforced oligomerization of an IKKβ mutant defective in forming homotypic interactions restores kinase activation. Homotypic interactions allow IKKβ molecules to transautophosphorylate one another on their activation loops. Finally, the oligomerization of IKKβ is stimulated by tumor necrosis factor α in cultured cells. Our findings support a model whereby ligand-induced homotypic interactions between IKKβ molecules result in IKKβ phosphorylation and consequently IKK activation. [ABSTRACT FROM AUTHOR]

The article discusses manipulating orientation of organic emitters remains a formidable challenge in organic light-emitting diodes. Topics include expansion of the acceptor plane of thermally activated delayed fluorescence emitters has demonstrated to selectively modulate emitting dipole orientation; and the expanded acceptor plane of PXZPyPM and PXZTAZPM resulted in a 15 to 18% increase in horizontal ratios of emitting dipole orientation.