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As an important halophyte in the Yellow River Delta, the Amaranthaceae C3Suaeda salsa (L.) Pall. has attracted much attention for the "red carpet" landscape, and could be simply divided into red and green phenotypes according to the betacyanin content in the fleshy leaves. However, S. salsa has not been sequenced yet, which limited people's understanding of this species at the molecular level. We constructed a high‐quality chromosome‐scale reference genome by combining high‐throughput sequencing, PacBio single molecule real‐time sequencing, and Hi‐C sequencing techniques with a genome size of 445.10 Mb and contigs N50 of 2.94 Mb. Through the annotation of the S. salsa genome, 298.76 Mb of the repetitive sequences and 23 965 protein‐coding genes were identified, of which the proportion of long terminal repeats type in the repetitive sequences was the most abundant, about 50.74% of the S. salsa genome. Comparative genomics indicated that S. salsa underwent a whole‐genome duplication event about 146.15 million years ago (Ma), and the estimated divergence time between S. salsa and Suaeda aralocaspica was about 16.9 Ma. A total of four betacyanins including betanidin, celosianin II, amaranthin and 6′‐O‐malonyl‐celosianin II were identified and purified in both phenotypes, while two significantly up‐regulated betacyanins (celosianin II and amaranthin) may be the main reason for the red color in red phenotype. In addition, we also performed transcriptomics and metabolomics in both phenotypes to explore the molecular mechanisms of pigment synthesis, and a series of structural genes and transcription factors concerning with betacyanin production were selected in S. salsa. [ABSTRACT FROM AUTHOR]

Time-dependent failure possibility-based design optimization (T-PBDO) can minimize the general cost while meeting the failure possibility requirement of aircraft structure in the service life. The accuracy of the T-PBDO solution obtained by existing efficient methods may be problematic in the case of nonlinear performance functions or multiple minimum performance target points. To overcome this limitation, this paper proposes a new double-loop method based on the adaptive kriging (AK) model and fuzzy simulation (FS), referred to as DL-AK-FS, is used to efficiently solve T-PBDO. In DL-AK-FS, to replace the real constraint performance function for dealing with the time-dependent failure possibility (TDFP) constraint, the inner loop is to adaptively construct a single-loop kriging model of the constraint performance function in the FS candidate sample pool. The outer loop is to search the optimal design parameters by optimization algorithm. The kriging model is first built in an augmented space that is spanned by design parameters and fuzzy inputs, and then it is adaptively and timely updated during the optimization iteration. Moreover, the strategy of reducing the size of the FS candidate sample pool is adopted to further improve the efficiency of analyzing the inner TDFP while ensuring the accuracy of the optimization solution. The strategy of combining FS with the AK model can extend the engineering applicability of the DL-AK-FS in estimating the inner TDFP, which is not limited by the complexity of the time-dependent performance function. The optimization results show that the proposed DL-AK-FS method in this paper is efficient and accurate for solving T-PBDO. [ABSTRACT FROM AUTHOR]

Background: Birth weight is considered not only to undermine future growth, but also to induce lifelong diseases; the aim of this study is to explore the relationship between birth weight and adult bone mass.Methods: We performed multivariable regression analyses to assess the association of birth weight with bone parameters measured by dual-energy X-ray absorptiometry (DXA) and by quantitative ultrasound (QUS), independently. We also implemented a systemic Mendelian randomization (MR) analysis to explore the causal association between them with both fetal-specific and maternal-specific instrumental variables.Results: In the observational analyses, we found that higher birth weight could increase the adult bone area (lumbar spine, β-coefficient= 0.17, P < 2.00 × 10-16; lateral spine, β-coefficient = 0.02, P = 0.04), decrease bone mineral content-adjusted bone area (BMCadjArea) (lumbar spine, β-coefficient= - 0.01, P = 2.27 × 10-14; lateral spine, β-coefficient = - 0.05, P = 0.001), and decrease adult bone mineral density (BMD) (lumbar spine, β-coefficient = - 0.04, P = 0.007; lateral spine; β-coefficient = - 0.03, P = 0.02; heel, β-coefficient = - 0.06, P < 2.00 × 10-16), and we observed that the effect of birth weight on bone size was larger than that on BMC. In MR analyses, the higher fetal-specific genetically determined birth weight was identified to be associated with higher bone area (lumbar spine; β-coefficient = 0.15, P = 1.26 × 10-6, total hip, β-coefficient = 0.15, P = 0.005; intertrochanteric area, β-coefficient = 0.13, P = 0.0009; trochanter area, β-coefficient = 0.11, P = 0.03) but lower BMD (lumbar spine, β-coefficient = - 0.10, P = 0.01; lateral spine, β-coefficient = - 0.12, P = 0.0003, and heel β-coefficient = - 0.11, P = 3.33 × 10-13). In addition, we found that the higher maternal-specific genetically determined offspring birth weight was associated with lower offspring adult heel BMD (β-coefficient = - 0.001, P = 0.04).Conclusions: The observational analyses suggested that higher birth weight was associated with the increased adult bone area but decreased BMD. By leveraging the genetic instrumental variables with maternal- and fetal-specific effects on birth weight, the observed relationship could be reflected by both the direct fetal and indirect maternal genetic effects. [ABSTRACT FROM AUTHOR]

Meiosis, which produces haploid progeny, is critical to ensuring both faithful genome transmission and genetic diversity. Proteasomes play critical roles at various stages of spermatogenesis, including meiosis, but the underlying mechanisms remain unclear. The atypical proteasomes, which contain the activator PA200, catalyze the acetylationdependent degradation of the core histones in elongated spermatids and DNA repair in somatic cells. We show here that the testis-specific proteasome subunit a4s/PSMA8 is essential for male fertility by promoting proper formation of spermatoproteasomes, which harbor both PA200 and constitutive catalytic subunits. Immunostaining of a spermatocyte marker, SYCP3, indicated that meiosis was halted at the stage of spermatocytes in the a4s-deficient testes. a4s stimulated the in vitro degradation of the acetylated core histones, instead of nonacetylated histones, by the PA200-proteasome. Deletion of a4s blocked degradation of the core histones at DNA damage loci in spermatocytes, leading to meiotic arrest at metaphase I. Thus, a4s is required for histone degradation at meiotic DNA damage loci, proper progression of meiosis, and fertility in males by promoting proper formation of spermatoproteasomes. These results are important for understanding male infertility and might provide potential targets for male contraception or treatment of male infertility. [ABSTRACT FROM AUTHOR]

This study investigated the physiological and ecological changes in P. sepium Bunge and elucidated the physiological regulatory mechanisms underlying the adaptation of P. sepium to drought stress in shell sand. Drought stress led to a significant decrease in the net photosynthesis rate (Pn) and respiration rate of leaves and a decrease in low-intensity light-use efficiency (LUE) and light ecological amplitude. An increase in drought stress led to a considerable decrease in the photosynthetic electron transport rate in the P. sepium leaves and a significant increase in the amount of light energy dissipated as heat. In addition, the photosynthesis process suffered from severe photoinhibition. P. sepium plants counteracted the effects of drought stress primarily by increasing their peroxidase (POD) activity and by regulating membrane lipid peroxidation by secreting greater numbers of osmotic adjustment substances (proline (Pro) and soluble sugars (Ss)) and malondialdehyde (MDA). As drought stress increased, both the stem sap flow rate and the cumulative sap flow of P. sepium decreased considerably. P. sepium Bunge adapts to drought stress through interregulatory activity between photosynthesis, water-related physiological activities, and physiological and biochemical processes, and this species exhibits relatively high adaptive plasticity to drought. [ABSTRACT FROM AUTHOR]

This study aimed to determine whether and how the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide affects the chemoresistance and chemosensitivity of pancreatic cancer cells to gemcitabine in vitro and in vivo. The GLP-1R and protein kinase A (PKA) levels were compared between the human pancreatic cancer cell line PANC-1 and the gemcitabine-resistant cell line PANC-GR. The in vitro effects of liraglutide on the cell proliferation and apoptosis as well as the nuclear factor-kappa B NF-κB expression levels of PANC-GR cells were evaluated. In addition, a mouse xenograft model of human pancreatic cancer was established by s.c. injection of PANC-1 cells, and the effects of liraglutide on the chemosensitivity were evaluated in vitro and in vivo. In contrast to PANC-1 cells, PANC-GR cells exhibited lower expression levels of GLP-1R and PKA. Incubation with liraglutide dose dependently inhibited the growth, promoted the apoptosis, and increased the expression of GLP-1R and PKA of PANC-GR cells. Similar effects of liraglutide were observed in another human pancreatic cancer cell line MiaPaCa-2/MiaPaCa-2-GR. Either the GLP-1R antagonist Ex-9, the PKA inhibitor H89, or the NF-κB activator lipopolysaccharide (LPS) could abolish the antiproliferative and proapoptotic activities of liraglutide. Additionally, each of these agents could reverse the expression of NF-κB and ABCG2, which was decreased by liraglutide treatment. Furthermore, liraglutide treatment increased the chemosensitivity of pancreatic cancer cells to gemcitabine, as evidenced by in vitro and in vivo experiments. Thus, GLP-1R agonists are safe and beneficial for patients complicated with pancreatic cancer and diabetes, especially for gemcitabine-resistant pancreatic cancer. [ABSTRACT FROM AUTHOR]

Objective: We conducted a Mendelian randomization study to investigate the associations of genetically predicted serum 25-hydroxyvitamin D (S-25OHD), calcium (S-Ca), and parathyroid hormone (S-PTH) levels with type 2 diabetes (T2DM).Research Design and Methods: Seven, six, and five single nucleotide polymorphisms (SNPs) associated with S-25OHD, S-Ca, and S-PTH levels, respectively, were used as instrumental variables. Data on T2DM were available for 74,124 case subjects with T2DM and 824,006 control subjects. The inverse variance-weighted method was used for the primary analyses, and the weighted median and Mendelian randomization (MR)-Egger methods were used for supplementary analyses.Results: Genetically predicted S-25OHD but not S-Ca and S-PTH levels were associated with T2DM in the primary analyses. For 1 SD increment of S-25OHD levels, the odds ratio (OR) of T2DM was 0.94 (95% CI 0.88-0.99; P = 0.029) in an analysis based on all seven SNPs and 0.90 (95% CI 0.83-0.98; P = 0.011) in an analysis based on three SNPs within or near genes involved in vitamin D synthesis. Only the association based on the SNPs involved in vitamin D synthesis remained in the weighted median analysis, and no pleiotropy was detected (P = 0.153). Pleiotropy was detected in the analysis of S-Ca (P = 0.013). After correcting for this bias using MR-Egger regression, the OR of T2DM per 1 SD increment of S-Ca levels was 1.41 (95% CI 1.12-1.77; P = 0.003).Conclusions: Modest lifelong higher S-25OHD levels were associated with reduced odds of T2DM, but the association was only robust for SNPs in the vitamin D synthesis pathway. The possible role of S-Ca levels for T2DM development requires further research. [ABSTRACT FROM AUTHOR]

BRUCE/Apollon is a membrane-associated inhibitor of apoptosis protein that is essential for viability and has ubiquitin-conjugating activity. On initiation of apoptosis, the ubiquitin ligase Nrdp1/RNF41 promotes proteasomal degradation of BRUCE. Here we demonstrate that BRUCE together with the proteasome activator PA28γ causes proteasomal degradation of LC3-I and thus inhibits autophagy. LC3-I on the phagophore membrane is conjugated to phosphatidylethanol-amine to form LC3-II, which is required for the formation of autophagosomes and selective recruitment of substrates. SIP/CacyBP is a ubiquitination-related protein that is highly expressed in neurons and various tumors. Under normal conditions, SIP inhibits the ubiquitination and degradation of BRUCE, probably by blocking the binding of Nrdp1 to BRUCE. On DNA damage by topoisomerase inhibitors, Nrdp1 causes monoubiquitination of SIP and thus promotes apoptosis. However, on starvation, SIP together with Rab8 enhances the translocation of BRUCE into the recycling endosome, formation of autophagosomes, and degradation of BRUCE by optineurin-mediated autophagy. Accordingly, deletion of SIP in cultured cells reduces the autophagic degradation of damaged mitochondria and cytosolic protein aggregates. Thus, by stimulating proteasomal degradation of LC3-I, BRUCE also inhibits autophagy. Conversely, SIP promotes autophagy by blocking BRUCE-dependent degradation of LC3-I and by enhancing autophagosome formation and autophagic destruction of BRUCE. These actions of BRUCE and SIP represent mechanisms that link the regulation of autophagy and apoptosis under different conditions. [ABSTRACT FROM AUTHOR]

Abstract The fatigue life prediction of solder joints under random vibration load is one of the most important aspect in design of packaging. A fatigue-life estimation in the frequency domain is proved to have advantages in comparison to the time-domain estimation. This paper presents a comparison of the fatigue life prediction of solder joints under random vibration load by several popular frequency domain methods, including the narrow-band, the Wirsching–Light, the single-moment, the Empirical α 0.75 , the Tovo–Benasciutti, the Zhao–Baker, and the Dirlik methods. The comparison between these selected frequency domain methods and the traditional Steinberg method was investigated with the help of the relative error. Results indicate that most spectral methods are accurate than the Steinberg method, the Tovo–Benasciutti method is proved to be the best method for the life estimation of solder joints suited not only to the BGA package but also to the PoP package. Highlights • Our research shows that most spectral methods are more accurate than the Steinberg method except for the narrow-band. • We find that the majority methods are conservative tend to underestimate the fatigue life of the solder joints. • The Tovo–Benasciutti is found to be the best in dealing with the vibration-fatigue estimation of the solder joints. [ABSTRACT FROM AUTHOR]

Background: This study is to compare the effects of Liraglutide and Metformin alone or combined treatment on the cardiac function in T2DM patients complicated with CAD. Methods: 120 T2DM patients were included at Endocrinology Department of Tianjin First Center Hospital (Tianjin, China) from April 2012 to September 2013. The study contained two sections. Section 1: 30 patients in group 1 was treated with Liraglutide (Novo Nordisk) (1.2 mg/d), and 30 patients in group 2 with Metformin (Shiguibao) (1500 mg/d) for 24 weeks. Section 2: 30 patients in group1 was treated with Liraglutide (1.8 mg/d) and 30 in group 2 with Liraglutide (1.2mg/d) plus Metformin (1500 mg/d) for 24 weeks. Fasting blood glucose (FBG), postprandial glucose (PPG), glycated hemoglobin (HbA1c), body mass index (BMI), blood pressure (BP), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), C reactive protein (CRP), left ventricular end-diastolic diameter (LVEDD), ejection fraction (EF) and the ratio of early (E) to late (A) ventricular filling velocities (E/A ratio) were measured before and after the 24-week treatment. Results: After 24-week treatment, when blood glucose level was controlled in 4 groups, Liraglutide alone treatment showed better improvements than on all measuring except TG in Section 1, however, combined treatment of Liraglutide and Metformin showed better improvements on all measuring except BMI, TG and BP in Section 2. Conclusions: With similar glycemic control, the Liraglutide (1.2 mg/d) monotherapy showed the better effects than either Metformin alone, or combination of Liraglutide and Metformin on lipid metabolism and cardiovascular function. [ABSTRACT FROM AUTHOR]

Paraoxonase 1 gene (PON1) polymorphisms and dietary vegetable and fruit intake are both established determinants of ischemic stroke (IS). However, little is known about whether these factors jointly influence the risk of IS. We analyzed the main effects of PON1, as well as the interactions between PON1 and dietary vegetable or fruit intake with the risk of total IS and its subtypes in a family-based case-control study conducted among 2158 Chinese participants (1007 IS cases and 1151 IS-free controls) from 918 families. Conditional logistic regression models, with each family as a stratum, were used to examine the association between rs662 and IS. Gene-diet interactions were tested by including a cross-product term of dietary vegetable or fruit intake by rs662_G allele count in the models. Each copy of the PON1 rs662_G allele was associated with 28% higher risk of total IS (p = 0.008) and 32% higher risk of large artery atherosclerosis subtype (LAA) (p = 0.01). We observed an interaction between rs662 and vegetable intake for both total IS (p = 0.006) and LAA (p = 0.02) after adjustment for covariates. Individuals who carry the rs662_A allele may benefit to a greater extent from intake of vegetables and thus be more effectively protected from ischemic stroke, whereas carriers of the G allele may still remain at greater risk for ischemic stroke due to their genetic backgrounds even when they consume a high level of vegetables. More studies are needed to replicate our findings among other populations. [ABSTRACT FROM AUTHOR]

The vibration reliability of lead-free solder joints of Package-on-Package (PoP) is investigated by experimental tests and finite element method (FEM) simulations in this paper. A 14 × 14 mm two-tier PoP module was selected for this study. The natural frequencies and modes were determined by FEM and verified by experimental tests. The printed circuit board (PCB) assemblies are tested under harmonic vibration. Vibration test results show that the vibration reliability of top package is better than the bottom package, and the outermost corner solder joints of the bottom package are the critical solder joints for the PoP under vibration loading. The stress characteristics of solder joints obtained by FEM are well correlated with the experimental results. Failure mechanism analysis indicates that the bottom solder joints become the most vulnerable part of the PoP under vibration due to the bigger relative displacements between the PCB and the bottom package. The micro-structural analysis indicates that cracks usually originate in the bottleneck position of the solder balls, extend within bulk solder and then propagate along the interface between the IMC layer and the bulk solder. The influence of bottom solder joints standoff for vibration reliability was analyzed by FEM as well. Results show that the higher the bottom solder joints' standoff, the more difficult the failure for the PoP assembly. [ABSTRACT FROM AUTHOR]

Density functional theory (DFT) and time-dependent DFT calculations were performed to evaluate the influence of substituent effect of (1) R = 4-Me, (2) R = 4-OMe, and (3) R = 2,3-OC6H4 on the phenyl ring of (C∧C*)PtII(acac) (C∧C* = phenylimidazole, acac = acetylacetone), respectively, on absorption and phosphorescent spectra properties, as well as the radiative and nonradiative processes. We found that emissions of complexes 2 and 3 originate from the Kasha-like T1 state, whereas that of complex 1 originates from non-Kasha T2 state. Compared with the emission of complex 1, the emission peaks of 2 and 3 are red-shifted, which is attributed to p-π and π-π conjugation effects resulting from the electron-donating groups -OCH3 and -OC6H4 with ligand C∧C*, respectively. The radiative rate constants (κr) of 2 and 3 are larger than that of 1, namely, κr(1) < κr(2) < κr(3), indicating that κr can be efficiently increased by enlarging π-conjugation at the main ligand of (C∧C*)PtII(acac), which can cause the increase of spin-orbit coupling (SOC) matrix elements. At the same time, the activation energy barriers for the rate-limiting step can be largely raised accompanied by enlarging the ability of electron-donation of the substituent group at the main ligand of (C∧C*)PtII(acac), which can cause the decrease of the nonradiative rate constant (κnr), namely, κnr(1) > κnr(2) > κnr(3). According to ΦP = κr/(κr + κnr), the quantum yields should have the sequence ΦP(1) < ΦP(2) < ΦP(3), which is in accordance with the experiment. In addition, to guide experimental synthesis of highly efficient (C∧C*)PtII(acac), a new complex 4 through extending the π-conjugation in the C∧C* ligand of (C∧C*)PtII(acac) was theoretically designed, which has a larger quantum yield than 1-3. [ABSTRACT FROM AUTHOR]

Infection with hepatitis A virus (HAV) is a major cause of acute hepatitis globally and it is important to identify the mechanisms of HAV replication. Glucose-regulated protein 78 (GRP78) is an endoplasmic reticulum (ER) chaperone and serves a role in unfolded protein response pathways. Previous studies have demonstrated that GRP78 functions as an endogenous antiviral factor. In the present study, two loss-of-function studies using GRP78 were completed to elucidate the role of GRP78 in HAV infection. HAV replication was observed to be enhanced by deficient GRP78 although GRP78-deficiency also led to lower expression of ER stress molecules downstream of GRP78. Therefore, GRP78 appears to be a potential novel defensive molecule against HAV in hepatocytes. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a predominantly male disease in which the androgen receptor (AR) serves an important pathogenic role in hepatocarcinogenesis. Fatty acid metabolism also contributes to hepatocarcinogenesis and is associated with the prognosis of cancer. The present study aimed to investigate the effects of the AR on fatty acid metabolism-associated gene expression in human hepatoma cell lines. AR-expression plasmids or control plasmids were transiently transfected into the human HCC cell lines Huh7 and HepG2. After 48 h, cellular protein and RNA were extracted and the expression of AR was confirmed by western blotting. Complementary DNA was synthesized and subjected to a quantitative polymerase chain reaction-based array to examine the expression of 84 fatty acid metabolism-associated genes. Overexpression of AR significantly downregulated the expression of 11 fatty acid metabolism-associated genes in Huh7 cells and 35 in HepG2 cells. The overexpression of AR also resulted in the upregulation of 6 fatty acid metabolism genes in HepG2 cells; however, it had no effect in Huh7 cells. Acyl-coenzyme A (CoA) thioesterase 7 and acyl-CoA oxidase 3 were downregulated in both cell lines. In conclusion, upregulation of AR via overexpression led to the disturbance of fatty acid metabolism-associated gene expression in human HCC cells. Therefore, the AR may serve a role in hepatocarcinogenesis via the regulation of hepatocellular fatty acid metabolism. [ABSTRACT FROM AUTHOR]

In this study, we developed a rapid, specific, and sensitive loop-mediated isothermal amplification technique combined with a lateral flow dipstick (LAMP-LFD) method to detect Salmonella targeting the siiA gene in powdered infant formula (PIF). The specificity of the detection method (LAMP-LFD) approached 100% using 21 Salmonella and 31 non-Salmonella bacterial strains. This detection method exhibited high sensitivity limits for pure cultures at 3.7 cfu/mL and in PIF at 2.2 cfu/g without enrichment. To evaluate the applicability of the LAMP-LFD method, we detected 60 positive PIF samples and 20 negative PIF samples. The results showed that the method of LAMP-LFD had a high diagnostic specificity of 100% for detection of Salmonella in PIF. To reduce incidence of LAMP contamination, we applied propidium monoazide (PMA) to eliminate carryover contamination of LAMP. At the same time, we found that PMA does not affect observation of LFD for measurement of LAMP signal. The results verified that the method of LAMP-LFD targeting the siiA gene is rapid, accurate, and sensitive for Salmonella detection in PIF, and that PMA shows great potential to be widely used to eliminate the amplicon contamination risk generated by the highly sensitive LAMP reaction in the detection process. [ABSTRACT FROM AUTHOR]

This paper presents a general methodology to predict the fatigue life of the Package-on-Package (PoP) under random vibration loading by means of vibration tests and finite element (FE) simulation. The behavior of the critical solder joints of the PoP under vibration loading was accurately described by FE model using ANSYS software and confirmed by modal analysis and linear sweep tests. The stress-life (S-N) curve of the PoP solder joints was obtained by the sinusoidal fatigue vibration tests and FE simulations to characterize the fatigue properties of the PoP under vibration. The comparison of the S-N curves of the SAC305 solder joints in different structures indicates the S-N curve of the SAC305 solder joints depends on the package structure. With the same fatigue cycles, the stress levels for the current 3D package is the smallest compared with the other 2D package due to the stacked structure of the PoP. Spectrum analysis for the random vibration tests was performed by the FE simulations to acquire the stress response power spectral density (PSD) of the critical solder joint. A specific frequency domain approach based on the Palmgren-Miner's rule was established to predict the fatigue life of the PoP under random vibration. Results show that simulated fatigue life matches well with the random vibration test results, which implies that this approach could be a potential method for the predication of fatigue life of the 3D packaging under random vibration. [ABSTRACT FROM AUTHOR]

Background: This study aimed to analyze quantitative correlation between the posterior malleolus fracture and fixation and the rotational stability of the ankle and to explore supplementary surgical indications for posterior malleolus fracture. Methods: Twenty fresh frozen cadaver specimens were selected and dissected. Based on the tibial insertion of the ligament complex, the model for the supination external rotation stage 3 ankle fracture with a posterior malleolar fragment and syndesmosis diastasis was created. The area threshold of the posterior tibial insertion of posterior malleolus fracture was biomechanically assessed and the difference of the antirotating ability stiffness of the ankle between simple posterior malleolus fixation and simple syndesmotic fixation was analyzed statistically. Results: The tibial insertion of posterior inferior tibiofibular ligament and inferior transverse tibiofibular ligament complex was relatively broad, and its width decreased as the distance from the joint line increased. Biomechanical analysis showed that: the threshold of posterior area of posterior malleolus fracture was 1/4S; posterior malleolus fixation provided better rotational stability than syndesmotic fixation (P < 0.01). Conclusion: The surgical indications for posterior malleolus fracture should consider simultaneously the restoration of the axial and rotational stability of the ankle. Simple posterior malleolus fracture fixation is recommended when the syndesmosis is unstable and the area ratio of posterior tibial insertion of posterior malleolus fracture is greater than or equal to 1/4. Syndesmotic fixation is proposed to restore and maintain the rotational stability of the ankle when the syndesmosis is unstable and the area ratio is less than 1/4. Regardless of the area ratio, the surgical indication only depends on the impact of the posterior malleolus fracture on the axial stability of tibiotalar joint, the involved articular surface area, and the displacement degree of posterior malleolus fragment, when the syndesmosis is stable. [ABSTRACT FROM AUTHOR]

In this paper, the Taguchi method and finite-element analysis (FEA) were used to improve the vibration reliability of the package-on-package (PoP) assembly and to achieve an optimal design of the PoP under random vibration loading. A finite-element model of the PoP assembly was developed, and experimental modal tests were performed to verify the finite-element model. Four geometry parameters of the PoP were chosen as the variable factors, including body size of PoP, bottom solder joint standoffs, thickness of bottom substrate, and top solder joint standoffs. The volume averaged von Mises stress of the critical solder joint obtained by FEA was chosen as the quality factor, and an L9 ( 3^4) orthogonal array was applied for Taguchi experiment to estimate the effects of the four factors and find the optimal design of the PoP on the vibration reliability. It is found that bottom solder joint standoffs have an important effect on the reliability, and more than 36% of the volume averaged Von Mises stress could be reduced by the optimal design. [ABSTRACT FROM PUBLISHER]

The ancient Chinese wild rice (Zizania latifolia (Griseb) Turcz) (CWR) has valuable biological and medicinal functions. To assess the advantages lost in modern cultivated rice after domestication, we compared the composition of bioactive compounds and the results of proteomic analysis with those of Indica rice (N22). We used routine methods to determine the protein, total dietary fiber, amino acid, mineral substance, plant secondary metabolites, and amino acid composition of CWR and N22. The protein and mineral contents of CWR were two times that of N22, and the levels of calcium, potassium, magnesium, chromium, iron, and zinc were significantly higher than those of N22 (P < .05). There was *7.6 times more dietary fiber in CWR than in N22, but fewer carbohydrates (P < .05). Anthocyanins and chlorophyll were detected in CWR, but were absent from N22. Compared with N22, CWR had 53, 19, and 5.4 times higher (P < .05) levels of saponins, flavonoids, and plant sterols, respectively. The amino acid score of CWR was 66.6, which was significantly higher than N22. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) indicated that the main seed proteins of CWR were glutelins, including both acid and alkaline subunits, which were approximately twice those of N22. To investigate the differences in protein profiles between CWR and N22, we conducted two-dimensional electrophoresis (2-DE) analysis of the total proteins in the seeds of the two rice species. 2-DE gels revealed 19 differentially expressed proteins. Information obtained from peptide mass fingerprinting indicates that glutelin precursor caffeoyl coenzyme A (CoA) O-methyltransferase and putative bithoraxoid-like protein can provide good gene sources for improving rice quality. [ABSTRACT FROM AUTHOR]

Background: The problem of learning causal influences from data has recently attracted much attention. Standard statistical methods can have difficulty learning discrete causes, which interacting to affect a target, because the assumptions in these methods often do not model discrete causal relationships well. An important task then is to learn such interactions from data. Motivated by the problem of learning epistatic interactions from datasets developed in genome-wide association studies (GWAS), researchers conceived new methods for learning discrete interactions. However, many of these methods do not differentiate a model representing a true interaction from a model representing non-interacting causes with strong individual affects. The recent algorithm MBS-IGain addresses this difficulty by using Bayesian network learning and information gain to discover interactions from high-dimensional datasets. However, MBS-IGain requires marginal effects to detect interactions containing more than two causes. If the dataset is not high-dimensional, we can avoid this shortcoming by doing an exhaustive search. Results: We develop Exhaustive-IGain, which is like MBS-IGain but does an exhaustive search. We compare the performance of Exhaustive-IGain to MBS-IGain using low-dimensional simulated datasets based on interactions with marginal effects and ones based on interactions without marginal effects. Their performance is similar on the datasets based on marginal effects. However, Exhaustive-IGain compellingly outperforms MBS-IGain on the datasets based on 3 and 4-cause interactions without marginal effects. We apply Exhaustive-IGain to investigate how clinical variables interact to affect breast cancer survival, and obtain results that agree with judgements of a breast cancer oncologist. Conclusions: We conclude that the combined use of information gain and Bayesian network scoring enables us to discover higher order interactions with no marginal effects if we perform an exhaustive search. We further conclude that Exhaustive-IGain can be effective when applied to real data. [ABSTRACT FROM AUTHOR]

Background: Ubiquitination is a very important process in protein post-translational modification, which has been widely investigated by biology scientists and researchers. Different experimental and computational methods have been developed to identify the ubiquitination sites in protein sequences. This paper aims at exploring computational machine learning methods for the prediction of ubiquitination sites using the physicochemical properties (PCPs) of amino acids in the protein sequences. Results: We first establish six different ubiquitination data sets, whose records contain both ubiquitination sites and non-ubiquitination sites in variant numbers of protein sequence segments. In particular, to establish such data sets, protein sequence segments are extracted from the original protein sequences used in four published papers on ubiquitination, while 531 PCP features of each extracted protein sequence segment are calculated based on PCP values from AAindex (Amino Acid index database) by averaging PCP values of all amino acids on each segment. Various computational machine-learning methods, including four Bayesian network methods (i.e., Naïve Bayes (NB), Feature Selection NB (FSNB), Model Averaged NB (MANB), and Efficient Bayesian Multivariate Classifier (EBMC)) and three regression methods (i.e., Support Vector Machine (SVM), Logistic Regression (LR), and Least Absolute Shrinkage and Selection Operator (LASSO)), are then applied to the six established segment-PCP data sets. Five-fold cross-validation and the Area Under Receiver Operating Characteristic Curve (AUROC) are employed to evaluate the ubiquitination prediction performance of each method. Results demonstrate that the PCP data of protein sequences contain information that could be mined by machine learning methods for ubiquitination site prediction. The comparative results show that EBMC, SVM and LR perform better than other methods, and EBMC is the only method that can get AUCs greater than or equal to 0.6 for the six established data sets. Results also show EBMC tends to perform better for larger data. Conclusions: Machine learning methods have been employed for the ubiquitination site prediction based on physicochemical properties of amino acids on protein sequences. Results demonstrate the effectiveness of using machine learning methodology to mine information from PCP data concerning protein sequences, as well as the superiority of EBMC, SVM and LR (especially EBMC) for the ubiquitination prediction compared to other methods. [ABSTRACT FROM AUTHOR]

Objective. To investigate the geneenvironment interaction between smoking and single nucleotide polymorphisms (SNPs), using Immunochip material, on the risk of developing either of two serologically defined subsets of RA. Methods. Interaction between smoking and 133 648 genetic markers from the Immunochip was examined for two RA subsets, defined by the presence or absence of ACPA. A total of 1590 ACPA-positive and 891 ACPA-negative cases were compared with 1856 controls in the Swedish Epidemiological Investigation of RA (EIRA) casecontrol study. Logistic regression models were used to determine the presence of interaction. The proportion attributable to interaction was calculated for each smokingSNP pair. Replication was carried out in an independent dataset from northern Sweden. To further validate and extend the results, interaction analysis was also performed using genome-wide association studies data on EIRA individuals. Results. In ACPA-positive RA, 102 SNPs interacted significantly with smoking, after Bonferroni correction. All 102 SNPs were located in the HLA region, mainly within the HLA class II region, 51 of which were replicated. No additional loci outside chromosome 6 were identified in the genome-wide association studies validation. After adjusting for HLA-DRB1 shared epitope, 15 smokingSNP pairs remained significant for ACPA-positive RA, with 8 of these replicated (loci: BTNL2, HLA-DRA, HLA-DRB5, HLA-DQA1, HLA-DOB and TAP2). For ACPA-negative RA, no smokingSNP pairs passed the threshold for significance. Conclusion. Our study presents extended gene variation patterns involved in genesmoking interaction in ACPA-positive, but not ACPA-negative, RA. Notably, variants in HLA-DRB1 and those in additional genes within the MHC class II region, but not in any other gene regions, showed interaction with smoking. [ABSTRACT FROM AUTHOR]

We are in the era of abundant 'big' or 'high-dimensional' data. These data afford us the opportunity to discover predictors of an event of interest, and to estimate occurrence of the event based on values of these predictors. For example, 'genome-wide association studies' examine millions of single-nucleotide polymorphisms (SNPs), along with disease status. We can learn SNPs that affect disease status from these data sets, and use the knowledge learned to predict disease likelihood. Owing to the large number of features, it is difficult for many prediction methods to use all the features directly. The ReliefF algorithm ranks a set of features in terms of how well they predict a target. It can be used to identify good predictors, which can then be provided to a prediction method. We compared the performance of eight prediction methods when predicting binary outcomes using high-dimensional discrete data sets. We performed two-stage prediction, where ReliefF is used in the first stage to identify good predictors. Bayesian network (BN)-based methods performed best overall. Furthermore, ReliefF did not improve their performance. The BN-based methods use the Bayesian Dirichlet Equivalent Uniform score to evaluate candidate models, and use BN inference algorithms to perform prediction. This score and these algorithms were developed for discrete variables. This perhaps explains why they perform better in this domain. Many prediction methods are available, and researchers have little reason for choosing one over the other in the domain of binary prediction using high-dimensional data sets. Our results indicate that the best choices overall are BN-based methods. [ABSTRACT FROM AUTHOR]

Background: Drowning is common worldwide. Rescue efforts attempted by untrained bystanders often lead to the death of the primary drowning victim (PDV), the rescuer or both. Our study aimed to inform prevention by identifying risk factors in rescuer drowning. Methods: Data on drowning rescue incidents reported online in mainland China, 2013, were reviewed. Information on the drowning incidents, PDVs and rescuers were retrieved for analysis. Results: A total of 225 rescue incidents were identified, of which 14 were victim-rescuer drowning incidents (VRDIs) (6.2 %). A person-to-person rescue by swimming to PDVs was the most commonly used method (58.9 %). Resuscitation was given immediately to 35.5 % of PDVs after rescue. The mortality rate of the rescuers (13.3 %) was similar to that of the PDVs (11.5 %) (X2 = 0.5, p =0.49). Being an adult (OR = 0.2, 95 % CI: 0.1-0.5) and other than the first rescuer (OR = 0.4, 95 % CI: 0.2-0.9) decreased the risk of rescuers drowning. Conclusions: Most of the currently employed life-saving methods are dangerous and even potentially life threatening. The idea of "rescuers' safety first" should be embraced, especially with teenage and child rescuers, who should never be encouraged to rescue others without first guaranteeing their own safety. Promotion of basic rescue skills should be implemented in the general public. [ABSTRACT FROM AUTHOR]

Background: Drowning is common worldwide. Rescue efforts attempted by untrained bystanders often lead to the death of the primary drowning victim (PDV), the rescuer or both. Our study aimed to inform prevention by identifying risk factors in rescuer drowning. Methods: Data on drowning rescue incidents reported online in mainland China, 2013, were reviewed. Information on the drowning incidents, PDVs and rescuers were retrieved for analysis. Results: A total of 225 rescue incidents were identified, of which 14 were victim-rescuer drowning incidents (VRDIs) (6.2 %). A person-to-person rescue by swimming to PDVs was the most commonly used method (58.9 %). Resuscitation was given immediately to 35.5 % of PDVs after rescue. The mortality rate of the rescuers (13.3 %) was similar to that of the PDVs (11.5 %) (χ2 = 0.5, p =0.49). Being an adult (OR = 0.2, 95 % CI: 0.1–0.5) and other than the first rescuer (OR = 0.4, 95 % CI: 0.2–0.9) decreased the risk of rescuers drowning. Conclusions: Most of the currently employed life-saving methods are dangerous and even potentially life threatening. The idea of “rescuers’ safety first” should be embraced, especially with teenage and child rescuers, who should never be encouraged to rescue others without first guaranteeing their own safety. Promotion of basic rescue skills should be implemented in the general public. [ABSTRACT FROM AUTHOR]

A weak interaction was found between the two methyl groups in the complexes of XCH3-CH3BH2 (X=F, CN, NO2, HCO, and SOCH3), where the former methyl group acts as a Lewis acid and the latter one as a Lewis base. This directional interaction has small interaction energy, accompanied with some small changes in geometry and spectroscopy. Stronger Lewis acids FYH3 (Y=Si, Ge, and Sn) as well as Lewis bases CH3BeH and CH3MgH were compared. Dispersion energy is the major source of attraction and electrostatic contribution grows up to exceed dispersion energy for stronger interactions. [ABSTRACT FROM AUTHOR]

Abstract: The boron(B)–nitrogen(N) co-doping ultra-small diameter (5,0) and (4,0) single-walled carbon nanotubes (SWCNTs) have been investigated by using the first-principles pseudopotential plane wave method. The results show that B–N pairs are easy to dope into ultra-small diameter zigzag nanotubes, which have numbers of differences with other large diameter nanotubes, and the B–N co-doping configurations are the energetically stable structures. Furthermore, by introducing B–N pairs, the (5,0) and (4,0) SWCNTs both transform from metal to semiconductor. These ultra-small diameter nanotubes have potential to be applied in semiconductor integrated circuit of extremely small size. [Copyright &y& Elsevier]

The purpose of this investigation is to develop and evaluate a new Bayesian network (BN)-based patient survivorship prediction method. The central hypothesis is that the method predicts patient survivorship well, while having the capability to handle high-dimensional data and be incorporated into a clinical decision support system (CDSS). We have developed EBMC_Survivorship (EBMC_S), which predicts survivorship for each year individu-ally. EBMC_S is based on the EBMC BN algorithm, which has been shown to handle high-dimensional data. BNs have excellent architecture for decision support systems. In this study, we evaluate EBMC_S using the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset, which concerns breast tumors. A 5-fold cross-validation study indicates that EMBC_S performs better than the Cox proportional hazard model and is comparable to the random survival forest method. We show that EBMC_S provides additional information such as sensitivity analyses, which covariates predict each year, and yearly areas under the ROC curve (AUROCs). We conclude that our investigation supports the central hypothesis. [ABSTRACT FROM AUTHOR]

Isogeopyxins A–C (1 – 3), three new diterpenoids with ent -kaurane, ent -pimarane, and ent -abietane scaffolds, respectively, along with six known ent -kauranoids, were isolated from the fermentation culture of Geopyxis sp. XY93 inhabiting the leaves of Isodon parvifolia. Their structures were elucidated by interpretation of spectroscopic data, and single crystal X-ray diffraction. It marks the first time that ent -kauranoids, characteristic metabolites of Isodon species, have been isolated from an associated endophytic fungus. [Display omitted] • Chemical investigation on endophytic Geopyxis sp. XY93 of Isodon parvifolia led to the discovery of 9 diterpenoids. • Characteristic metabolites of Isodon species were isolated from an associated endophytic fungus for the first time. • ent -Kauranoids from Geopyxis sp. XY93 exhibited good cytotoxic effects against liver cancer cells. [ABSTRACT FROM AUTHOR]

Highlights: [•] Small energy gaps exists in both (3,3) and (5,0) tubes after B/N co-doping. [•] In most case the energy gaps increase with increasing the symmetry destruction factor δ. [•] The electronic structures of B/N co-doped SWCNTs with B- or N-rich impurities are converted into metal from semiconductor. [Copyright &y& Elsevier]

Background: Epiretinal implants based on microelectro-mechanical system (MEMS) technology with a polyimide (PI) material are being proposed for application. Many kinds of non-photosensitive PIs have good biocompatibility and stability as typical MEMS materials for implantable electrodes. However, the effects of MEMS microfabrication, sterilization and implantation using a photosensitive polyimide (PSPI) microelectrode array for epiretinal electrical stimulation has not been extensively examined. Methods: A novel PSPI (Durimide 7510) microelectrode array for epiretinal electrical stimulation was designed, fabricated based on MEMS processing and microfabrication techniques. The biocompatibility of our new microelectrode was tested in vitro using an MTT assay and direct contact tests between the microelectrode surface and cells. Electrochemical impedance characteristics were tested based on a three-electrode testing method. The reliability and stability was evaluated by a chronic implantation of a non-functional array within the rabbit eye. Histological examination and SEM were performed to monitor possible damage of the retina and microelectrodes. Electrically evoked potentials (EEPs) were recorded during the acute stimulation of the retina. Results: The substrate was made of PSPI and the electrode material was platinum (Pt). The PSPI microelectrode array showed good biocompatibility and appropriate impedance characteristics for epiretinal stimulation. After a 6-month epiretinal implantation in the eyes of rabbits, we found no local retinal toxicity and no mechanical compression caused by the array. The Pt electrodes adhesion to the PSPI remained stable. A response to electrical stimuli was with recording electrodes lying on the visual cortex. Conclusion: We provide a relevant design and fundamental characteristics of a PSPI microelectrode array. Strong evidences on testing indicate that implantation is safe in terms of mechanical pressure and biocompatibility of PSPI microelectrode arrays on the retina. The dual-layer process we used proffers considerable advantages over the more traditional single-layer approach and can accommodate much many electrode sites. This lays the groundwork for a future, high-resolution retinal prosthesis with many more electrode sites based on the flexible PSPI thin film substrate. [ABSTRACT FROM AUTHOR]

Cell therapies such as CAR−T have demonstrated significant clinical successes, driving the investigation of immune cell surface engineering using natural and synthetic materials to enhance their therapeutic performance. However, many of these materials do not fully replicate the dynamic nature of the extracellular matrix (ECM). This study presents a cell surface engineering strategy that utilizes phase‐separated peptide coacervates to decorate the surface of immune cells. We meticulously designed a tripeptide, Fmoc−Lys−Gly−Dopa−OH (KGdelta; Fmoc=fluorenylmethyloxycarbonyl; delta=Dopa, dihydroxyphenylalanine), that forms coacervates in aqueous solution via phase separation. These coacervates, mirroring the phase separation properties of ECM proteins, coat the natural killer (NK) cell surface with the assistance of Fe3+ ions and create an outer layer capable of encapsulating monoclonal antibodies (mAb), such as Trastuzumab. The antibody‐embedded coacervate layer equips the NK cells with the ability to recognize cancer cells and eliminate them through enhanced antibody‐dependent cellular cytotoxicity (ADCC). This work thus presents a unique strategy of cell surface functionalization and demonstrates its use in displaying cancer‐targeting mAb for cancer therapies, highlighting its potential application in the field of cancer therapy. [ABSTRACT FROM AUTHOR]

Cell therapies such as CAR−T have demonstrated significant clinical successes, driving the investigation of immune cell surface engineering using natural and synthetic materials to enhance their therapeutic performance. However, many of these materials do not fully replicate the dynamic nature of the extracellular matrix (ECM). This study presents a cell surface engineering strategy that utilizes phase‐separated peptide coacervates to decorate the surface of immune cells. We meticulously designed a tripeptide, Fmoc−Lys−Gly−Dopa−OH (KGdelta; Fmoc=fluorenylmethyloxycarbonyl; delta=Dopa, dihydroxyphenylalanine), that forms coacervates in aqueous solution via phase separation. These coacervates, mirroring the phase separation properties of ECM proteins, coat the natural killer (NK) cell surface with the assistance of Fe3+ ions and create an outer layer capable of encapsulating monoclonal antibodies (mAb), such as Trastuzumab. The antibody‐embedded coacervate layer equips the NK cells with the ability to recognize cancer cells and eliminate them through enhanced antibody‐dependent cellular cytotoxicity (ADCC). This work thus presents a unique strategy of cell surface functionalization and demonstrates its use in displaying cancer‐targeting mAb for cancer therapies, highlighting its potential application in the field of cancer therapy. [ABSTRACT FROM AUTHOR]

Background: There is a critical need for a rapid and sensitive pathogen detection method for septic patients. This study aimed to investigate the diagnostic efficacy of Digital droplet polymerase chain reaction (ddPCR) in identifying pathogens among suspected septic patients. Methods: We conducted a prospective pilot diagnostic study to clinically validate the multiplex ddPCR panel in diagnosing suspected septic patients. A total of 100 sepsis episodes of 89 patients were included in the study. Results: In comparison to blood culture, the ddPCR panel exhibited an overall sensitivity of 75.0% and a specificity of 69.7%, ddPCR yielded an additional detection rate of 17.0% for sepsis cases overall, with a turnaround time of 2.5 h. The sensitivity of ddPCR in the empirical antibiotic treatment and the non-empirical antibiotic treatment group were 78.6% versus 80.0% (p > 0.05). Antimicrobial resistance genes were identified in a total of 13 samples. Whenever ddPCR detected the genes beta-lactamase-Klebsiella pneumoniae carbapenemase (blaKPC) or beta-lactamase-New Delhi metallo (blaNDM), these findings corresponded to the cultivation of carbapenem-resistant gram-negative bacteria. Dynamic ddPCR monitoring revealed a consistent alignment between the quantitative ddPCR results and the trends observed in C-reactive protein and procalcitonin levels. Conclusions: Compared to blood culture, ddPCR exhibited higher sensitivity for pathogen diagnosis in suspected septic patients, and it provided pathogen and drug resistance information in a shorter time. The quantitative results of ddPCR generally aligned with the trends seen in C-reactive protein and procalcitonin levels, indicating that ddPCR can serve as a dynamic monitoring tool for pathogen load in septic patients. [ABSTRACT FROM AUTHOR]

Background: The interaction between loci to affect phenotype is called epistasis. It is strict epistasis if no proper subset of the interacting loci exhibits a marginal effect. For many diseases, it is likely that unknown epistatic interactions affect disease susceptibility. A difficulty when mining epistatic interactions from high-dimensional datasets concerns the curse of dimensionality. There are too many combinations of SNPs to perform an exhaustive search. A method that could locate strict epistasis without an exhaustive search can be considered the brass ring of methods for analyzing high-dimensional datasets. Methodology/Findings: A SNP pattern is a Bayesian network representing SNP-disease relationships. The Bayesian score for a SNP pattern is the probability of the data given the pattern, and has been used to learn SNP patterns. We identified a bound for the score of a SNP pattern. The bound provides an upper limit on the Bayesian score of any pattern that could be obtained by expanding a given pattern. We felt that the bound might enable the data to say something about the promise of expanding a 1-SNP pattern even when there are no marginal effects. We tested the bound using simulated datasets and semi-synthetic high-dimensional datasets obtained from GWAS datasets. We found that the bound was able to dramatically reduce the search time for strict epistasis. Using an Alzheimer's dataset, we showed that it is possible to discover an interaction involving the APOE gene based on its score because of its large marginal effect, but that the bound is most effective at discovering interactions without marginal effects. Conclusions/Significance: We conclude that the bound appears to ameliorate the curse of dimensionality in high- dimensional datasets. This is a very consequential result and could be pivotal in our efforts to reveal the dark matter of genetic disease risk from high-dimensional datasets. [ABSTRACT FROM AUTHOR]

Abstract: Subtle changes in the chemical structure or the composition of surface bound ligands on quantum dots (QDs) remain difficult to detect. Here we describe a facile setup for fluorescence detection coupled capillary electrophoresis (CE-FL) and its application in monitoring ligand displacement on QDs through metal-affinity driven assembly. We also describe the use of CE-FL to monitor amide bond cleavage by a specific protease, based on Förster resonance energy transfer (FRET) between Cy5 and QDs spaced by a hexahistidine peptide (H6–Cy5). CE-FL allowed separation of unbound QDs and ligand bound QDs and also revealed an ordered assembly of H6–Cy5 on QDs. In a ligand displacement experiment, unlabeled hexahistidine peptide gradually displaced surface bound H6–Cy5 until finally reaching equilibrium. The displacement intermediates were clearly separated on CE-FL. Proteolytic cleavage of surface bound H6–Cy5 by thrombin was monitored by CE-FL through mobility shift, peak broadening, and FRET changes. Enzymatic parameters thus obtained were comparable with those measured by fluorescence spectroscopy. [Copyright &y& Elsevier]

Extramedullary hematopoiesis (EMH), defined as the presence of hematopoiesis outside bone marrowand peripheral blood, occurs as a compensatory phenomenon in several hematologic disorders and bone marrow dysfunction. EMH predominantly affects reticuloendothelial system including the spleen, liver and lymph nodes. Here, we report a rare case of multiple intracranial meningeal EMH. A 37-year-oldwomanwas anemic with graduallyworsening vision for 8 months. Multiple extra-axial masses were found on imaging and the patient underwent the biopsy for the left frontotemporal lesion. Final diagnosis was multiple intracranial meningeal EMH. Treatment of fractionated external beam radiotherapy resulted in marked symptomatic improvement. This case indicates that although the diagnosis of meningeal EMH is difficult, there is a need to consider EMHin the differential diagnosis of anemic patients with tumor-like mass lesions in extramedullary sites. [ABSTRACT FROM AUTHOR]

Background: A genome-wide association study (GWAS) typically involves examining representative SNPs in individuals from some population. A GWAS data set can concern a million SNPs and may soon concern billions. Researchers investigate the association of each SNP individually with a disease, and it is becoming increasingly commonplace to also analyze multi-SNP associations. Techniques for handling so many hypotheses include the Bonferroni correction and recently developed Bayesian methods. These methods can encounter problems. Most importantly, they are not applicable to a complex multilocus hypothesis which has several competing hypotheses rather than only a null hypothesis. A method that computes the posterior probability of complex hypotheses is a pressing need Methodology/Findings: We introduce the Bayesian network posterior probability (BNPP) method which addresses the difficulties. The method represents the relationship between a disease and SNPs using a directed acyclic graph (DAG) model, and computes the likelihood of such models using a Bayesian network scoring criterion. The posterior probability of a hypothesis is computed based on the likelihoods of all competing hypotheses. The BNPP can not only be used to evaluate a hypothesis that has previously been discovered or suspected, but also to discover new disease loci associations. The results of experiments using simulated and real data sets are presented. Our results concerning simulated data sets indicate that the BNPP exhibits both better evaluation and discovery performance than does a p-value based method. For the real data sets, previous findings in the literature are confirmed and additional findings are found Conclusions/Significance: We conclude that the BNPP resolves a pressing problem by providing a way to compute the posterior probability of complex multi-locus hypotheses. A researcher can use the BNPP to determine the expected utility of investigating a hypothesis further. Furthermore, we conclude that the BNPP is a promising method for discovering disease loci associations [ABSTRACT FROM AUTHOR]

Background: Gene-gene epistatic interactions likely play an important role in the genetic basis of many common diseases. Recently, machine-learning and data mining methods have been developed for learning epistatic relationships from data. A well-known combinatorial method that has been successfully applied for detecting epistasis is Multifactor Dimensionality Reduction (MDR). Jiang et al. created a combinatorial epistasis learning method called BNMBL to learn Bayesian network (BN) epistatic models. They compared BNMBL to MDR using simulated data sets. Each of these data sets was generated from a model that associates two SNPs with a disease and includes 18 unrelated SNPs. For each data set, BNMBL and MDR were used to score all 2-SNP models, and BNMBL learned significantly more correct models. In real data sets, we ordinarily do not know the number of SNPs that influence phenotype. BNMBL may not perform as well if we also scored models containing more than two SNPs. Furthermore, a number of other BN scoring criteria have been developed. They may detect epistatic interactions even better than BNMBL. Although BNs are a promising tool for learning epistatic relationships from data, we cannot confidently use them in this domain until we determine which scoring criteria work best or even well when we try learning the correct model without knowledge of the number of SNPs in that model. Results: We evaluated the performance of 22 BN scoring criteria using 28,000 simulated data sets and a real Alzheimer's GWAS data set. Our results were surprising in that the Bayesian scoring criterion with large values of a hyperparameter called α performed best. This score performed better than other BN scoring criteria and MDR at recall using simulated data sets, at detecting the hardest-to-detect models using simulated data sets, and at substantiating previous results using the real Alzheimer's data set. Conclusions: We conclude that representing epistatic interactions using BN models and scoring them using a BN scoring criterion holds promise for identifying epistatic genetic variants in data. In particular, the Bayesian scoring criterion with large values of a hyperparameter α appears more promising than a number of alternatives. [ABSTRACT FROM AUTHOR]

Escherichia coli play an important ecological role within resistant bacteria populations, and can be used as a bio-indicator of antimicrobial resistance. The aim of the present study was to use this feature of E. coli to investigate the prevalence of antimicrobial resistance and the degree of cross-species transmission of bacteria in pigs and poultry in China. A total of 592 E. coli strains, isolated from pigs and poultry (healthy and diseased animals), were tested for resistance to 22 antimicrobials representing eight antimicrobial drug types. E. coli isolates had high rates of resistance to ampicillin (99.5%), doxycycline (95.6%), tetracycline (93.4%), trimethoprim-sulfamethoxazole (74.3%), amoxicillin (65.1%), streptomycin (54.7%), and chloramphenicol (50.2%). Resistance to cephalosporins, quinolones, and aminoglycosides was also quite prevalent. The majority (81%) of isolates demonstrated multi-antimicrobial resistance, most commonly to 5-6 different antimicrobial types. One isolate was resistant to all 22 antimicrobials. Twenty-two cultures exhibiting multi-antimicrobial resistance were analysed by pulsed-field gel electrophoresis (PFGE) to assess their distribution between farms. Three distinct PFGE types were identified, indicating inter-farm transmission of multi-antimicrobial-resistant bacteria. The study confirmed the presence and transmission of multi-antimicrobial resistant E. coli strains amongst pigs and poultry in China and highlights the urgent need for appropriate monitoring programmes. [ABSTRACT FROM AUTHOR]

In this study, a series of 3-D interconnected porous scaffolds with various pore diameters and porosities was fabricated by freeze-drying with non-toxic biodegradable waterborne polyurethane (WBPU) emulsions of different concentration. The structures of these porous scaffolds were characterized by scanning electron microscopy (SEM), and the pore diameters were calculated using CIAS 3.0 software. The pores obtained were 3-D interconnected in the scaffolds. The scaffolds obtained at different pre-freeze temperatures showed a pore diameter ranging from 2.8 to 99.9 μm with a pre-freezing temperature of -60°C and from 13.1 to 229.1 μm with a pre-freezing temperature of -25°C. The scaffolds fabricated with WBPU emulsions of different concentration at the same pre-freezing temperature (-25°C) had pores with mean pore diameter between 90.8 and 39.6 μm and porosity between 92.0 and 80.0%, depending on the emulsion concentration. The effect of porous structure of the scaffolds on adhesion and proliferation of human umbilical vein endothelial cells (HUVECs) cultured in vitro was evaluated using the MTT assay and environmental scanning electron microscopy (ESEM). It was found that the better adhesion and proliferation of HUVECs on 3-D scaffolds of WBPU with relative smaller pore diameter and lower porosity than those on scaffolds with larger pore and higher porosity and film. Our work suggests that fabricating a scaffold with controllable pore diameter and porosity could be a good method to be used in tissue-engineering applications to obtain carriers for cell culture in vitro. [ABSTRACT FROM AUTHOR]

Escherichia coli isolates from diseased pigs were examined for antimicrobial susceptibility to 12 antimicrobials and possession of virulence genes (VGs), and then grouped according to the phylogenetic background and genetic relatedness. Associations between antimicrobial resistance (AMR) and VGs and between AMR and phylogenetic group were subsequently assessed. The results showed that most isolates (91%) were epidemiologically unrelated. Multiple antimicrobial-resistant phenotypes (≥5 antimicrobials) were observed in 89% of E. coli strains and the most frequent types of resistance were to sulfamethoxazole (95%), tetracycline (94%), chloramphenicol (89%), and streptomycin (84%). The majority of isolates belonged to phylogenetic group A (84%). The most prevalent VG was EAST1 (64%), followed by Stx2e (63%) and eae (47%). Resistance to ceftiofur was associated with the presence of certain VGs, whereas resistance to doxycycline and kanamycin was associated with the absence of certain VGs. These findings suggest that multidrug resistance phenotypes, a variety of VGs, and the clear associations between resistance and VGs are commonly present in E. coli strains from diseased pigs. These results indicate that there is a great need for surveillance programs in China to monitor AMR in pathogenic E. coli strains. [ABSTRACT FROM AUTHOR]

Violacein is a bacteria-originated indolocarbazole pigment with potential applications due to its various bioactivities such as anti-tumor, antiviral, and antifungal activities. However, stable mass production of this pigment is difficult due to its low productivities and the instability of wild-type violacein-producing strains. In order to establish a stable and efficient production system for violacein, the violacein synthesis pathway from a new species of Duganella sp. B2 was reconstructed in different bacterial strains including Escherichia coli, Citrobacter freundii, and Enterobacter aerogenes by using different vectors. The gene cluster that encodes five enzymes involved in the violacein biosynthetic pathway was first isolated from Duganella sp. B2, and three recombinant expression vectors were constructed using the T7 promoter or the alkane-responsive promoter PalkB. Our results showed that violacein could be stably synthesized in E. coli, C. freundii, and E. aerogenes. Interestingly, we found that there were great differences between the different recombinant strains, not only in the protein expression profiles pertaining to violacein biosynthesis but also in the productivity and composition of crude violacein. Among the host strains tested, the crude violacein production by the recombinant C. freundii strain reached 1.68 g L−1 in shake flask cultures, which was 4-fold higher than the highest production previously reported in flask culture by other groups. To the best of our knowledge, this is the first report on the efficient production of violacein by genetically engineered strains. [ABSTRACT FROM AUTHOR]

Dynamic regulation models for voltage-sourced converter (VSC) based flexible ac transmission system (FACTS) controllers are described in this paper. The dynamic models can then be used to analyze these FACTS controller's capability to improve the capability of a power transfer path. The contributions of this paper include showing that the benefits of FACTS controllers are proportional to the MVA ratings and the benefits of multiple FACTS controllers are cumulative. Furthermore, the coupling of dc buses allowing active power circulation between multiple VSC FACTS controllers may offer additional improvement in transfer capability. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are characterized by their hematopoiesis-supporting and immunosuppressive capacity, while osteoclasts are main cell components in the endosteal hematopoietic stem cell niche and pivotal players in osteoimmunology. To clarify the association of these 2 kinds of cells, mouse CD11bmonocytes were cultured onto MSC layers in the presence or absence of macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-B ligand (RANKL). The results showed that MSCs independently supported osteoclast development and this effect was enhanced by M-CSF and RANKL. Interestingly, tumor necrosis factor- (TNF-)–stimulated MSCs turned to inhibit osteoclast formation and protect tusk slices from osteoclastic resorption. Real-time PCR and ELISA assays demonstrated that osteoprotegerin expression at both mRNA and protein levels in TNF-–stimulated MSCs was up-regulated, at least partially by activating the mitogen-activated protein kinase pathway. Furthermore, TNF-–stimulated MSCs maintained their immunophenotypic, multipotential differentiation and immunosuppressive characteristics. Moreover, MSCs treated with synovial fluid from rheumatoid arthritis patients modulated osteoclast generation in close relation with the TNF- levels. This study suggests that MSCs exhibit dual modulatory function on osteoclasts and the result might shed light on understanding the involvement of MSCs in the inflammatory diseases. [ABSTRACT FROM AUTHOR]

An analysis of Hawking radiation about apparent horizon in a FRW universe is performed by using the method developed in the paper (Banerjee, Majhi in JHEP 06:095 2008), in which the Hawking radiation of a black hole is treated as the quantum tunneling by Hamilton-Jacobi method beyond semiclassical approximation and then all the higher order quantum corrections can be given out. In our analysis, the Kodama vector instead of the Killing vector to define the energy of the particle plays a key role. We present our analysis under the Friedmann-Robertson-Walker like coordinate system and the much-like to Painlevé coordinate system respectively. The result show that the formulized procedure can be extended to fully analyse the Hawking radiation of a dynamical system. [ABSTRACT FROM AUTHOR]

Due to their ability to provide reactive power support and control active power flow, voltage-sourced-converter (VSC)-based flexible ac transmission system controllers can be used to improve the power transfer capability of congested transmission lines. A converter-based controller structure has the inherent feature to be used to provide shunt or series compensations. This inherent feature is utilized in the convertible static compensator installed at the New York Power Authority's Marcy substation, which can operate in 11 configurations of shunt and series compensations. Moreover, each configuration can be operated in different control modes. The paper presents a novel approach to model converter-based transmission controllers for load-flow calculations. The paper focuses on modeling converter-based controllers when two or more VSCs are coupled to a dc link (e.g., unified power-flow controller (UPFC), interline power-flow controller, and a generalized unified power-flow controller). This approach also allows efficient implementation of various VSC operating limits, where one or more VSCs are loaded to their rated capacity. A computer program incorporating this approach is developed to illustrate the maximum dispatchability of UPFC and IPFC in a large power system. [ABSTRACT FROM AUTHOR]

Abstract  Functionalized molecular sieve SBA-15 with trimethylchlorosilane was used as an inorganic filler in a poly(ethyleneoxide) (PEO) polymer matrix to synthesize a composite solid-state polymer electrolyte (CSPE) using LiClO4 as the doping salts, which is designated to be used for rechargeable lithium batteries. The methyl group-functionalized SBA-15 (fSBA-15) powder possesses more hydrophobic characters than SBA-15, which improves the miscibility between the fSBA-15 filler and the PEO matrix. The interaction between the fSBA-15 and PEO polymer matrix was investigated by scanning electron microscopy, X-ray diffraction, and differential scanning calorimetry. Linear sweep voltammetry and electrochemical impedance spectroscopy were employed to study the electrochemical stability windows, ionic conductivity, and interfacial stability of the CSPE. The temperature dependence of the change of the PEO polymer matrix in the CSPE from crystallization to amorphous phase was surveyed, for the first time, at different temperature by Fourier transform infrared emission spectroscopy. It has demonstrated that the addition of the fSBA-15 filler has improved significantly the electrochemical compatibility of the CSPE with a lithium metal electrode and enhanced effectively the ion conductivity of the CSPE. [ABSTRACT FROM AUTHOR]