Search

Based on the laser flash method, the selection of experimental parameters on the accuracy of measurement results for measuring thermal diffusivity is investigated in this paper. High purity graphite is employed as the experimental material. Three experimental parameters are taken into consideration, including specimen thickness, laser pulse power, and laser pulse width. Firstly, the principle of the laser flash method is introduced. Then, a numerical simulation model is established and independence tests are performed. In order to investigate the impact of different experimental parameters to the precision of the measurement results using the laser flash method, six thicknesses of the specimens, five laser pulse powers, and five laser pulse widths are selected for numerical simulation and LFA 427 measurement experiments. Finally, an orthogonal design method with three-factor and three-level is constructed to investigate the influence degree of these three factors on the measurement results. It is found that the laser pulse width has the most significant influence, while the laser pulse power has the least impact. For high purity graphite specimens, it is required to choose a thicker specimen, a lower laser pulse power, and a smaller laser pulse width to ensure better measurement accuracy. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia and dyslipidemia. Carvacrol (CAR) has demonstrated the potential to mitigate dyslipidemia. This study aims to investigate whether CAR can modulate blood glucose and lipid levels in a T2DM rat model by regulating short-chain fatty acids (SCFAs) and the GPR41/43 pathway. The T2DM rat model was induced by a high-fat diet combined with low-dose streptozocin injection and treated with oral CAR and/or mixed antibiotics. Fasting blood glucose, oral glucose tolerance, and insulin tolerance tests were assessed. Serum lipid parameters, hepatic and renal function indicators, tissue morphology, and SCFAs were measured. In vitro, high glucose (HG)-induced IEC-6 cells were treated with CAR, and optimal CAR concentration was determined. HG-induced IEC-6 cells were treated with SCFAs or/and GPR41/43 agonists. CAR significantly reduced blood lipid and glucose levels, improved tissue damage, and increased SCFA levels in feces and GPR41/43 expression in colonic tissues of T2DM rats. CAR also attenuated HG-induced apoptosis of IEC-6 cells and enhanced GPR41/43 expression. Overall, these findings suggest that CAR alleviates blood lipid and glucose abnormalities in T2DM rats by modulating SCFAs and the GPR41/43 pathway. [ABSTRACT FROM AUTHOR]

Amyloidogenic deposition of β-amyloid (Aβ) peptides in human brain involves not only the wild-type Aβ (wt-Aβ) sequences, but also posttranslationally modified Aβ (PTM-Aβ) variants. Recent studies hypothesizes that the PTM-Aβ variants may trigger the deposition of wt-Aβ, which underlies the pathology of Sporadic Alzheimer's disease. Among PTM-Aβ variants, the pyroglutamate-3-Aβ (pyroE3-Aβ) has attracted much attention becauseof their significant abundances and broad distributions in senile plaques and dispersible and soluble oligomers. pyroE3-specific antibodies are being tested as potential anti-Aβ drugs in clinical trials. However, evidence that support the triggering effect of pyroE3-Aβ on wt-Aβ in cells remain lacking, which diminishes its pathological relevance. We show here that cross-seeding with pyroE3-Aβ40 leads to accelerated extracellular and intracellular aggregation of wt-Aβ40 in different neuronal cells. Cytotoxicity levels are elevated through the cross-seeded aggregation, comparing with the self-seeded aggregation of wt-Aβ40 or the static presence of pyroE3-Aβ40 seeds. For the extracellular deposition in mouse neuroblastoma Neuro2a (N2a) cells, the cytotoxicity elevation correlates positively with the seeding efficiency. Besides aggregation rates, cross-seeding with pyroE3-Aβ40 also modulates the molecular level structural polymorphisms of the resultant wt-Aβ40 fibrils. Using solid-state nuclear magnetic resonance (ssNMR) spectroscopy, we identified key structural differences between the parent pyroE3/?E3 and wt-Aβ40 fibrils within their fibrillar cores. Structural propagation from seeds to daughter fibrils is demonstrated to be more pronounced in the extracellular seeding in N2a cells by comparing the ssNMR spectra from different seeded wt-Aβ40 fibrils, but less significant in the intracellular seeding process in human neuroblastoma SHSY5Y cells. [ABSTRACT FROM AUTHOR]

To enhance the accuracy of mechanical simulation in the directional solidification process of turbine blades for heavy-duty gas turbines, a new constitutive model that employs machine learning methods was developed. This model incorporates incremental learning and transfer learning, thus improves the predictive accuracy and generalization performance. To account for the anisotropy of the directionally solidified alloy, a deformation direction parameter is added to the model, enabling prediction of the stress-strain relationship of the alloy under different deformation directions. The predictive capabilities of both models are evaluated using correlation coefficient (R), average relative error (δ), and value of relative error (RE). Compared to the traditional model, the machine learning constitutive model achieves higher prediction accuracy and better generalization performance. This offers a new approach for the establishment of flow constitutive models for other directionally solidified and single-crystal superalloys. [ABSTRACT FROM AUTHOR]

Malaria kills more than 500,000 people yearly, mainly affecting Africa and Southeast Asia. The disease is caused by the protozoan parasite from the genus Plasmodium, with Plasmodium vivax and Plasmodium falciparum being the main species that cause the disease in humans. Although substantial progress has been observed in malaria research in the last years, the threat of the spread of Plasmodium parasites persists. Artemisinin-resistant strains of this parasite have been reported mainly in Southeast Asia, highlighting the urgent need to develop more effective and safe antimalarial drugs. In this context, natural sources, mainly from flora, remain underexplored antimalarial spaces. The present mini-review explores this space focusing on plant extracts and some of their isolated natural products with at least in vitro antiplasmodial effects reported in the literature comprising the last five years (2018–2022). [ABSTRACT FROM AUTHOR]

Responses to sedatives, analgesics and muscle relaxants vary among patients under general anesthesia, which could be ascribed to the disparities of clinical characteristics and genetic factors of individuals. Accumulating researches have indicated that gene polymorphisms of the receptors, transporters and metabolizing enzymes associated with anesthetics play a considerable role in their efficacy. However, a systematically summarized study on the mechanisms of gene polymorphisms on pharmacodynamics and pharmacokinetics of anesthetics is still lacking. In this paper, the recent researches on pharmacogenomics of sedatives, analgesics and muscle relaxants are comprehensively reviewed, and the contributions and mechanisms of polymorphisms to the differences of individual efficacy of these drugs are discussed, so as to provide guidance for the formulation of a rational anesthesia regimen for patients with various genotypes. [ABSTRACT FROM AUTHOR]

About 10% of children with congenital heart disease (CHD) have pulmonary arterial hypertension (PAH). In this study, we explored the diagnostic values of neutrophil-to-lymphocyte ratio (NLR) and Tei index for CHD-PAH in children. In order to complete the study, two hundred CHD children treated in our hospital from January 2015 to January 2017 were enrolled and divided into postoperative-PAH group (n=29) and no postoperative-PAH group (n=171) according to follow-up results. The peripheral blood was drawn after surgery, neutrophils and lymphocytes were measured by routine blood test, and NLR was calculated. Ventricular Tei index was determined by pulse Doppler, and the other basic data were compared. Factors affecting postoperative PAH were explored by multivariate analysis. The correlations of NLR and Tei index with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac output/pulmonary blood flow (CO/Qp), were analyzed. The structural equation model of PAH was constructed. According to receiver operating characteristic (ROC) curves, the optimal cutoff values of NLR and Tei index for evaluating postoperative PAH were investigated. It has been found that NLR and Tei index are closely related to CHD-PAH in children, which indirectly reflect the severity and have high diagnostic values. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of modified Wenyang Buxin decoction and routine therapy on cardiac function and serum levels of heart-type fatty acid binding protein (H-FABP), cardiac troponin-1 (cTnI) and angiopoietin-2 (Ang-2) in chronic heart failure (CHF) patients. Methods: A total of 120 CHF patients admitted to Zhejiang Province Rongjun Hospital (from January 2019 - January 2020) were selected for this study. They were randomly but equally distributed into groups A and B. All patients were given routine therapy such as diuretic treatment and detumescence, while those in group A received 150 mL of modified Wenyang Buxin decoction daily, in addition to routine therapy. At 2 months after therapy, cardiac function indices, serum H-FABP, cTnI and Ang-2 levels, hemorheology indices, traditional Chinese medicine (TCM) syndrome scores, and Chinese questionnaire of quality of life in cardiovascular patients (CQQC) scores of the two groups were evaluated. Results: After therapy, cardiac function indices, serum H-FABP, cTnI and Ang-2 levels, hemorheology indices as well as TCM syndrome score and CQQC score were significantly improved in group A, when compared with corresponding values in group B (p < 0.05). Conclusion: Modified Wenyang Buxin decoction and routine therapy improves serum biomarker levels, cardiac function and quality of life, and relieves clinical symptoms of CHF in patients. Therefore, this treatment approach may be useful in the management of CHF patients. [ABSTRACT FROM AUTHOR]

It is well known that chemical compositions and structural arrangements of materials have a great influence on their resultant properties. Diverse functional materials have been constructed by using either biomolecules (peptides, DNA, and RNA) in nature or artificially synthesized molecules (polymers and pillararenes). The relationships between traditional building blocks (such as peptides) have been widely investigated, for example how hydrogen bonds work in the peptide multistage assembly process. However, in contrast to traditional covalent bond-based building blocks-based assembly, suprastructures formed by noncovalent bonds are more influenced by specific bond features, but to date only a few results have been reported based on noncovalent bond-based building block multistage assembly. Here, three metal-organic cycles (MOCs) were used to show how coordination bonds influence the bimetallacycle conformation then lead to the topology differences of MOC multilevel ordered materials. It was found that the coordination linker (isophthalate-Pt-pyridine) is an important factor to tune the shape and size of the MOC-derived suprastructures. [ABSTRACT FROM AUTHOR]

In this paper, we study on the fractional nonlocal equation with the logarithmic nonlinearity formed by... [ABSTRACT FROM AUTHOR]

The article presents a study that explores the loss of activating transcription factor 4 (ATF4) leads to functional aging-like attrition of adult hematopoietic stem cells . It mentions that aging of hematopoietic stem cells (HSCs) directly contributes to dysfunction of hematopoietic and immune systems due to aging-associated alterations in HSC features.

Netrin-1, a secreted protein recently characterized as a relevant cancer therapeutic target, is the antiapoptotic ligand of the dependence receptors deleted in colorectal carcinoma and members of the UNC5H family. Netrin-1 is overexpressed in several aggressive cancers where it promotes cancer progression by inhibiting cell death induced by its receptors. Interference of its binding to its receptors has been shown, through the development of a monoclonal neutralizing antinetrin-1 antibody (currently in phase II of clinical trial), to actively induce apoptosis and tumor growth inhibition. The transcription factor p53 was shown to positively regulate netrin-1 gene expression. We show here that netrin-1 could be a target gene of the N-terminal p53 isoform Δ40p53, independent of full-length p53 activity. Using stable cell lines, harboring wild-type or null-p53, in which Δ40p53 expression could be finely tuned, we prove that Δ40p53 binds to and activates the netrin-1 promoter. In addition, we show that forcing immortalized human skeletal myoblasts to produce the Δ40p53 isoform, instead of full-length p53, leads to the up-regulation of netrin-1 and its receptor UNC5B and promotes cell survival. Indeed, we demonstrate that netrin-1 interference, in the presence of Δ40p53, triggers apoptosis in cancer and primary cells, leading to tumor growth inhibition in preclinical in vivo models. Finally, we show a positive correlation between netrin-1 and Δ40p53 gene expression in human melanoma and colorectal cancer biopsies. Hence, we propose that inhibition of netrin-1 binding to its receptors should be a promising therapeutic strategy in human tumors expressing high levels of Δ40p53. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) continue to attract increasing interest with respect to their applications as luminescent materials. The ordered structure of the metal-organic complex facilitates the selective integration of PAHs that can be tuned to function cooperatively. Here, a unique highly twisted anthracene-based organoplatinum metallacycle was prepared via coordination-driven selfassembly. Single-crystal X-ray diffraction analysis revealed that the metallacycle was twisted through the cooperation of strong π···π stacking interactions and steric hindrance between two anthracenebased ligands. Notably, the intramolecular twist and aggregation behavior introduced restrictions to the conformational change of anthracenes, which resulted in increased emission intensity of the metallacycle in solution. The emission behaviors and suprastructures based on the highly twisted metallacycle can be modulated by the introduction of different solvents. This study demonstrates that this metallacycle with highly twisted structure is a promising candidate for sensing and bioimaging applications. [ABSTRACT FROM AUTHOR]

The spectroscopic characteristics of Er-doped lead silicate glasses were investigated with respect to the effects of glass modifiers (Li+, Na+, K+, Mg2+, Ca2+, Sr2+, and Ba2+)with various optical basicities. Using the absorption spectra of the glasses, the Judd--Ofelt parameters of the glasses were calculated and examined, with an emphasis on the glass emission intensity ratio at 1572 nm. The spectra of the samples at low temperatures were examined, and the Stark splitting of Er3+ was investigated. The McCumber method was used to determine the emission cross sections of glasses. The SPM glass exhibited high values of full width at half maximum (51.24 nm) and the emission cross section at 1572 nm (1.908 x 10-21 cm²), with potential applications for guiding component design of 1.5-μm fiber lasers and amplifiers. [ABSTRACT FROM AUTHOR]

Since the advent of the microscope, it has been mainly used in the field of material science, and then it has been gradually applied to biomedical field with excellent results. As a cell analysis instrument rising in 1980s, microscope is also one of the most advanced scientific and technological achievements. Up to now, it is still one of the most reliable tools in biomedical image analysis. Based on the above advantages, the simulation video of midwifery suture wound is developed with the help of microscope. 50 primiparas in our hospital were selected as the experimental objects and were divided into observation group (n = 25) and control group (n = 25) according to the principle of random distribution. The observation group was sutured by traditional midwifery wound, while the control group was sutured by midwifery wound with the help of simulation video. The results showed that the two groups were compared from operation time, hospitalization time, wound healing time and the incidence of wound adverse reactions (wound bleeding, wound infection, imperfect suture and slow recovery, etc.), and 50 primiparas and experts were investigated by questionnaire respectively. The results showed that the healing rate of 100% of the wounds in the observation group was significantly higher than that in the control group, while the control group was only The healing rate was 84.28%, the operation time and hospitalization time were greatly reduced, and the difference between the groups was statistically significant (P < 0.05); experts and patients also highly appraised the simulation video system. Combined with the development of the simulation video system of the midwifery suture under the electron microscope, it is beneficial to the wound suture, accelerate the wound healing rate, reduce the occurrence of adverse events, and improve the discharge rate, which is worthy of wide application. [ABSTRACT FROM AUTHOR]

The availability of phosphorus (P) and nitrogen (N) constrain the ability of ecosystems to use resources such as light, water and carbon. In turn, nutrients impact the distribution of productivity, ecosystem carbon turnovers and their net exchange of CO2 with the atmosphere in response to variation of environmental conditions both in space and in time. In this study, we evaluated the performance of the global version of the land surface model ORCHIDEE-CNP (v1.2) which explicitly simulates N and P biogeochemistry in terrestrial ecosystems coupled with carbon, water and energy transfers. We used data from remote-sensing, ground-based measurement networks and ecological databases. Components of the N and P cycle at different levels of aggregation (from local to global) are in good agreement with data-driven estimates. When integrated for the period 1850 to 2017 forced with variable climate, rising CO2 and land use change, we show that ORCHIDEE-CNP underestimates the land carbon sink in the North Hemisphere (NH) during the recent decades, despite an a priori realistic GPP response to rising CO2. This result suggests either that other processes than CO2 fertilization which are omitted in ORCHIDEE-CNP, such as changes in biomass turnover, are predominant drivers of the northern land sink, and/or that the model parameterizations produce too strict emerging nutrient limitations on biomass growth in northern areas. In line with the latter, we identified biases in the simulated large-scale patterns of leaf and soil stoichiometry and plant P use efficiency pointing towards a too severe P limitations towards the poles. Based on our analysis of ecosystem resource use efficiencies and nutrient cycling, we propose ways to address the model biases by giving priority to better representing processes of soil organic P mineralization and soil inorganic P transformation, followed by refining the biomass production efficiency under increasing atmospheric CO2, phenology dynamics and canopy light absorption. [ABSTRACT FROM AUTHOR]

Background: Cutaneous wound healing is a complex, dynamic physiological process. Traditional methods of promoting wound healing are not always effective. Consequently, alternative modalities, such as photodynamic therapy (PDT), are needed. We examined the effectiveness and underlying mechanisms of PDT in a murine model of acute wound healing.///Methods: Two excisional wounds were produced, one on each side of the midline, in C57bL/6J mice. Methyl 5-aminolevulinate hydrochloride (MAL) was applied to the right-side wound. After 1 to 3 hours of incubation, the wound was irradiated with red light. The left-side wound was not treated with MAL or red light. On Day 14, the wounds were excised and subjected to histological and immunohistochemical analysis.///Results: During the first week, no difference was seen between the two sides. However, at week 2, PDT-treated wounds exhibited delayed re-epithelialization. On Day 14, hematoxylin and eosin (HE) staining showed a continuous epithelial lining in untreated wounds. In contrast, PDT-treated wounds partially lacked epithelium in the wound bed. Masson's Trichrome (MTC) staining showed a thicker dermis and more collagen fibers and inflammatory cells in PDT-treated wounds than in untreated wounds. Immunohistochemical analyses showed significantly fewer CD31+ blood vessels and greater collagen III density in PDT-treated wounds than in untreated wounds. However, treated and untreated wounds did not differ in collagen I density.///Conclusions: PDT delayed acute wound healing in a murine model of secondary intention wound healing. [ABSTRACT FROM AUTHOR]

Energy levels and E1, E2, M1, and M2 transitions rates are reported for the low-lying 41 levels of Ge(XVIII), belonging to the n = 3 states (1s22s22p6)3s23p3, 3s3p4, and 3s23p23d. High-accuracy calculations have been performed as benchmarks for accurate treatments of relativity, electron correlations, and QED effects in multivalence- electron systems. The calculated energy levels are in excellent agreement with the experimental results and the experimentally compiled energy values from the National Institute for Standards and Technology wherever available. The calculated values, including core-valence corrections, are found to be in a good agreement with other theoretical and experimental values. The present results are reported as benchmarks for future calculations and measurements. [ABSTRACT FROM AUTHOR]

Androgen insensitivity syndrome (AIS; OMIM 300068) is the most frequent cause of 46, XY disorders of sex development (DSD). However, the correlation between genotype and phenotype has not been determined. We conducted a systematic analysis of the clinical characteristics, hormone levels, ultrasonography data and histopathology of a 46, XY Chinese patient with AIS. The family was followed up for nearly 8 years. We applied whole-exome sequencing (WES) for genetic analysis of the pedigree and performed bioinformatic analysis of the identified variants. Human embryonic kidney 293T/17 (HEK293T/17) cells were transiently transfected with wild-type or mutant AR and MAP3K1 plasmid. Cell lysates were used to analyze androgen receptor (AR) production. A novel hemizygous AR variant (c.2070C>A, p. His690Glu) and a rare heterozygous MAP3K1 variant (c.778C>T, p. Arg260Cys) were identified by WES in the proband and her mother. Bioinformatic analysis predicted these two variants to be pathogenic. Multiple amino acid sequence alignments showed that p. His690 and p. Arg260 are conserved among various species. His690Glu is a mutation that decreased the AR production, whereas the Arg260Cys mutation increased the AR production. The novel compound variants of the AR and MAP3K1 genes also increased the production of AR protein. Thus, the phenotype of the patient may be caused by defects in both the AR and MAP3K1 signaling pathways. Compound variants of the AR and MAP3K1 genes resulted in a specific phenotype in this patient with AIS. WES might reveal genetic variants that explain the heterogeneity of AIS. [ABSTRACT FROM AUTHOR]

In recent years, medical imaging technology has rapidly spread in the modern medical industry, producing a large amount of medical image information. The purpose of this paper is how to combine the key means of image processing with medical images, providing doctors with efficient and convenient means of medical image search. This paper studies medical image segmentation, extraction and representation of feature, index and related retrieval techniques. Aiming at image segmentation, a PCNN image segmentation method based on canny edge detection is proposed. Based on the traditional gray histogram feature extraction technique, an adaptive weighted improved gray histogram method is proposed, and it is proved by experiments that this method can enhance some important features of the image. It is easier to calculate the similarity and help the doctor to find the image features of interest in the complex learning image. For the image indexing technology, used the artificial neural network BP algorithm to classify the image, proposed a diffusion matching algorithm based on image segmentation. In the corresponding feedback, the rough set and the support vector set can be better combined, and introduced corresponding feedback techniques to retrieve the image. Make full use of the rough set of big data processing, the benefits of redundant data's reduction, which can reduce SVM training data, can not only improve SVM classification efficiency, but also improve retrieval efficiency. Experimental results show that the improved corresponding feedback method has certain advantages in feedback accuracy and feedback speed. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore the effect of the treatment through autologous fibula graft and hollow needle fixation to treat femoral head cutting after dynamic hip screw (DHS) fixation. Methods: A total of 41 patients were admitted to the department of orthopedic trauma and received DHS fixation. Preoperative and postoperative harris score of hip function, limb shortening length and collodiaphysial angle between operation group (n = 11) and non-operation group (n = 13) were compared. Results: There was no difference between the two groups before surgery (P > 0.05). There was a difference between the preoperative and postoperative in the operation group (P < 0.05). The excellent and good rate of the hip function score in patients 6 months after the operation was 55.6%. In the operation group, the hip function score increased after surgery (P < 0.001). Except for two groups of patients before operation, there was a difference in the limb shortening length and collodiaphysial angle between the operation group and non-operation group in other time points after surgery (P < 0.001). Conclusion: The application of the autogenous fibula graft and hollow nail fixation was effective in treating femoral head cutting after DHS fixation, and patients’ subjective evaluation and objective indicators’ outcomes of follow up were satisfactory, which was worthy of clinical application. [ABSTRACT FROM AUTHOR]

Multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a multigene family with isoform-specific regulation of vascular smooth muscle (VSM) functions. In previous studies, we found that vascular injury resulted in VSM dedifferentiation and reduced expression of the CaMKII-γ isoform in medial wall VSM. Smooth muscle knockout of CaMKII-γ enhanced injury-induced VSM neointimal hyperplasia, whereas CaMKII-γ overexpression inhibited VSM proliferation and neointimal formation. In this study, we evaluated DNA cytosine methylation/demethylation as a mechanism for regulating CaMKII isoform expression in VSM. Inhibition of cytosine methylation with 5-Aza-2=-deoxycytidine significantly upregulated CaMKII-γ expression in cultured VSM cells and inhibited CaMKII-γ downregulation in organ-cultured aorta ex vivo. With the use of methylated cytosine immunoprecipitation, the rat Camk2g promoter was found hypomethylated in differentiated VSM, whereas injury- or cell culture-induced VSM dedifferentiation coincided with Camk2g promoter methylation and decreased expression. We report for the first time that VSM cell phenotype switching is accompanied by marked induction of thymine DNA glycosylase (TDG) protein and mRNA expression in injured arteries in vivo and in cultured VSM synthetic phenotype cells. Silencing Tdg in VSM promoted expression of CaMKII-γ and differentiation markers, including myocardin, and inhibited VSM cell proliferation and injury-induced neointima formation. This study indicates that CaMKII-γ expression in VSM is regulated by cytosine methylation/demethylation and that TDG is an important determinant of this process and, more broadly, VSM phenotype switching and function. [ABSTRACT FROM AUTHOR]

Anxiety is presumably driven by fear memory. Molecular profiles in the amygdala of mice with fear memory induced by psychological and physical stresses remain to be elucidated. Fear memory in mice was induced by a paradigm of social defeat. Physical and psychological stresses (PPS) to an intruder were given by attacks from an aggressive resident. Psychological stress (PS) to an observer was given by the witnessing of aggressor attacks. Amygdala tissues from these mice showing fear memory and anxiety vs. tissues from control mice were harvested to analyze mRNA and microRNA profiles by high-throughput sequencing. In the amygdala of intruders and observers with fear memory, the genes encoding 5-HTR1b, 5-HTR2a, DAR2, AChRM3, and IP3R1 are upregulated, whereas genes encoding GPγ11, GPγ13, GPγT2, RasC3, and P450 are downregulated, indicating that these molecules are involved in fear memory induced by physical/psychological stresses. In the comparison of intruders with observers, the upregulation of genes encoding 5-HTR6, GPγ8, P2R7, NFκ2, CREB3/1, and Itgα9 as well as the downregulation of genes encoding DAR5, 5-HTR1a, and HSP1a are involved in fear memory induced by physical stress. The upregulation of genes encoding DAR1, 5-HTR5a and SSR2/3 as well as the downregulation of AdRα1, CREB3/1, GPγ13 and GPγ8 are involved in fear memory induced by psychological stress. Results obtained by sequencing mRNA and microRNA profiles are consistent with results of quantitative RT-PCR analysis and dual-luciferase reporter assays performed for validation. In conclusion, fear memories and anxiety induced by PPS vs. PS are caused by the imbalanced regulation of different synapses and signaling pathways in the amygdala.NEW & NOTEWORTHY The current study identifies the molecular mechanism underlying fear memory and anxiety induced by psychological stress vs. physical stress, in which the imbalanced expression of microRNA-regulated mRNAs relevant to dopaminergic, adrenergic, and serotonergic synapses in the amygdala plays an important role. This result reveals different molecular profiles for psychological and physical stresses. [ABSTRACT FROM AUTHOR]

• The postbuckling response of rings under external pressure is analyzed theoretically. • The problem is studied by three strain-hardening ring models step by step. • Each strain-hardening model is solved by different analytical methods. • Analytical results correlate well with FEM results. The large deflection postbuckling behavior of rings under external pressure was studied theoretically and numerically. Rigid linear strain-hardening property was adopted to approximate the plastic behavior of the rings. Analytical models based on different theories were derived to describe the large deflection properties of postbuckling behavior. The influence of material properties and geometric parameter on the postbuckling response was investigated based on the proposed analytical models. Besides, finite element analyses were carried out to verify the validity of the proposed analytical models and the numerical results showed good agreement with the theoretical ones. [ABSTRACT FROM AUTHOR]

Highlights • Analytical analysis is presented for imperfect non-uniform shallow arch. • Criteria of occurrence of snap-through are derived by L'Hospital's rule for imperfect case. • Equal potential energy load is shown to coincide with buckle propation load of 3D shallow panel. • Asymptotical analysis reveals an interesting asymptotical structure for rigid end case when size of center region is small. Abstract This paper deals with analytical investigation of non-uniform circular shallow arch under a concentrated load considering imperfection effect under pinned-pinned boundary conditions. After characterizing the non-uniformity by three piecewise constant stiffness segments, governing equilibrium equations including imperfection effect are derived via least potential energy principle and criteria for possible occurrence of symmetric snap-through are explicitly presented by using L'Hospital's rule after identifying two modified slenderness parameters. The existence of an equal potential energy load is rigorously shown in a straightforward manner and its parametric dependence on imperfection and non-uniformity is discussed. The relationship between equal potential energy load and buckle propagation load is studied by 3D FEA of buckle propagation of corresponding non-uniform shallow panel. Moreover, two limiting cases including rigid end case and rigid center case are analyzed by employing augmented potential energy with Lagrangian multipliers. An asymptotical solution shows that a finite modified slenderness (independent of imperfection) is sufficient to ensure the occurrence of symmetric snap-through when dimension of center segment is approaching to zero in rigid end case and this conclusion holds when there is some rotational restraint at ends. For rigid center case, the closed-form criterion considering imperfection for symmetric snap-through occurrence is presented. Equal potential energy load for two limiting cases is derived and analyzed in detail. This paper is expected to enhance the understanding of stability of imperfect non-uniform shallow arch. Graphical abstract Image, graphical abstract [ABSTRACT FROM AUTHOR]

Background/Aims: Endoplasmic reticulum (ER) stress is an important event in atherosclerosis. Recent studies have shown that ER stress deregulates cholesterol metabolism via multiple pathways. This study aimed to determine the relationship between ER stress and lipid metabolism and to verify that upregulation of miR-33 is involved in this process. Methods: An atherosclerosis model was established in apolipoprotein E-deficient (ApoE-/-) mice fed a Western diet, and THP-1 derived macrophages were used in this study. Hematoxylin-eosin and Oil Red O staining were used to quantify the atherosclerotic plaques. 1,1'-Dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate labeled oxidized low-density lipoprotein binding assay and a Cholesterol Efflux Fluorometric Assay Kit were used to observe cholesterol uptake and efflux. The mRNA and protein levels of biomarkers associated with ER stress and cholesterol metabolism in atherosclerotic plaques and macrophages were evaluated by real-time PCR and western blotting, respectively. Immunofluorescence was used to observe alterations of ABCA1 localization. Small interfering RNAs were used to knock down CHOP and miR-33 in macrophages to alter CHOP and miR-33 expression. Results: Atherosclerotic lesions and systemic lipid levels were ameliorated after inhibition of ER stress (tauroursodeoxycholic acid) in vivo. In vitro studies confirmed that ER stress regulated the lipid catabolism of macrophages by promoting cholesterol uptake, inhibiting cholesterol efflux, and modulating the expression of related transporters. CHOP contributed to lipid metabolism disorder following ER stress. Furthermore, over-expression of miR-33 was involved in ER stress that induced lipid metabolism disorder in macrophages. These findings support a model of ER stress induction by oxidized low-density lipoprotein that affects macrophage lipid catabolism disorder. Conclusion: Our data shed new light on the relationship between ER stress and lipid metabolism in vivo and in vitro, and confirm that upregulation of miR-33 is involved in this process. The relationship between ER stress and miR-33 represents a novel target for the treatment of atherosclerosis. [ABSTRACT FROM AUTHOR]

In some forms of gait analysis, it is important to be able to capture when the heel strikes occur. In addition, in terms of video analysis of gait, it is important to be able to localise the heel where it strikes on the floor. In this study, a new motion descriptor, acceleration flow, is introduced for detecting heel strikes. The key frame of heel strike can be determined by the quantity of acceleration flow within the region of interest, and positions of the strike can be found from the centre of rotation caused by radial acceleration. Our approach has been tested on a number of databases which were recorded indoors and outdoors with multiple views and walking directions for evaluating the detection rate under various environments. Experiments show the ability of our approach for both temporal detection and spatial positioning. The immunity of this new approach to three anticipated types of noises in real CCTV footage is also evaluated in our experiments. The authors acceleration flow detector is shown to be less sensitive to Gaussian white noise, whilst being effective with images of low-resolution and with incomplete body position information when compared with other techniques. [ABSTRACT FROM AUTHOR]

Analytical investigation of collapse of a pinned non-uniform shallow circular arch under uniform radial pressure is presented in this paper. The non-uniformity is introduced by dividing the arch into three regions of constant stiffness. The equilibrium equations are obtained by using least potential energy principle. By proper nondimensionalization, the presented solution is independent of total length of the arch. And two modified slenderness parameters are identified which enables the result to be valid for any symmetric cross-section shape. Parametric study on different geometric parameters has been carried out on the snap-through buckling load and anti-symmetric bifurcation load. The validity of the analytical result is verified by comparison with FEA results. Criteria concerning four deformation modes are identified. We show there is an equal potential energy load for some non-uniform shallow arches by a straightforward deduction, the existence of which load is a necessary condition for the buckle propagation of a corresponding long shallow panel. Finally two limiting cases (rigid center case and rigid end case) with extreme non-uniformity are analytically studied by using augmented potential energy with Lagrangian multipliers. For rigid center case, closed-form condition for the possible occurrence of symmetric snap-through is presented. For rigid end case, an asymptotical analysis leads to a somewhat surprising critical value of slenderness which makes the snap-through buckling just possible. This paper intends to improve the understanding of the effect of non-uniformity on collapse of shallow arch under radial uniform pressure. [ABSTRACT FROM AUTHOR]

The collapse behavior of a non-uniform circular shallow arch is analytically studied for both fixed-fixed and pinned-pinned boundary conditions. The non-uniformity is characterized by three piecewise constant stiffness regions. The equilibrium equations are derived based on the least potential energy principle and the resulting solutions are presented by proper non-dimensionalization in a form independent of total length of the whole arch by identifying two modified slenderness parameters. Detailed parametric study of both stiffer center case and stiffer end case has been conducted to investigate the influence of various geometric parameters and distinctly different collapse behaviors are found for different boundary conditions. Some criteria are derived to identify the snap-through buckling. Moreover two limiting cases of extreme non-uniformity(rigid end case and rigid center case) are studied via the augmented potential energy with introduced Lagrangian multipliers. Through an asymptotical analysis, a finite modified slenderness parameter is shown to suffice to ensure the occurrence of snap-through buckling for rigid end case with pinned boundary conditions when the dimension of center region is approaching to zero. It is shown rigorously that the same conclusion holds even when there is some rotational restraint at the pinned ends. For rigid center case, closed-formed criteria are derived for snap-through buckling. Finally analysis has been carried out on the case where one part of the arch has large bending rigidity but moderate stretching rigidity. This paper aims to enhance the understanding of collapse behavior of non-uniform shallow arch under a central concentrated load for various boundary conditions. [ABSTRACT FROM AUTHOR]

We report a kinetic and mechanistic study on the title reactions, in which 102 was generated by the reaction of H2O2 with Cl2 and bubbled into an aqueous solution of guanine and 9-methylguanine (9MG) at different pH values. Oxidation kinetics and product branching ratios were measured using online electrospray ionization mass spectrometry coupled with absorption and emission spectrophotometry, and product structures were determined by collision-induced dissociation (CID) tandem mass spectrometry. Experiments revealed strong pH dependence of the reactions. The oxidation of guanine is noticeable only in basic solution, while the oxidation of 9MG is weak in acidic solution, increases in neutral solution, and becomes intensive in basic solution. 5-Guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp) were detected as the major oxidation products of guanine and 9MG, and Sp became dominant in basic solution. A reaction intermediate was captured in mass spectra, and assigned to gem-diol on the basis of CID measurements. This intermediate served as the precursor for the formation of Gh. After taking into account solution compositions at each pH, first-order oxidation rate constants were extracted for individual species: that is, 3.2-3.6 × 107 M-1 s-1 for deprotonated guanine, and 1.2 × 106 and 4.6-4.9 × 107 M-1 s-1 for neutral and deprotonated 9MG, respectively. Guided by approximately spin-projected density-functional-theory-calculated reaction potential energy surfaces, the kinetics for the initial 1O2 addition to guanine and 9MG was evaluated using transition state theory (TST). The comparison between TST modeling and experiment confirms that 1O2 addition is rate-limiting for oxidation, which forms endoperoxide and peroxide intermediates as determined in previous measurements of the same systems in the gas phase. [ABSTRACT FROM AUTHOR]

Grain size and weight are important determinants of rice yield. The identification of beneficial genes from wild rice that have been lost or weakened in cultivated rice has become increasingly important for modern breeding strategies. In this study, we constructed a set of chromosome segment substitution lines (CSSLs) of wild rice, Oryza rufipogon with the indica cultivar 9311 genetic background. Four grain-related traits, i.e., grain length (GL), grain width (GW), length-width ratio (LWR), and thousand grain weight (TGW), were screened across six environments. A total of 37 quantitative trait loci (QTLs) were identified in these environments and mapped to 12 chromosomes. Sixteen QTLs were detected in at least two environments, and two QTL clusters were observed on Chr. 4 and Chr. 8. Based on a comparative analysis with QTLs identified in previous studies, the CSSLs between Oryza rufipogon accessions and 9311 had high genetic diversity. Among the sixteen stable QTLs, seven for TGW, LWR, GL, and GW were not previously identified, indicating potentially novel alleles from wild rice. These CSSLs provide powerful tools for functional studies and the cloning of essential genes in rice; furthermore, we identified elite germplasm for rice variety improvement. [ABSTRACT FROM AUTHOR]

Abnormal glucose metabolism is critical in colorectal cancer (CRC) development. Expression of the pyruvate kinase (PK) M2 isoform, rather than the PKM1 isoform, serves important functions in reprogramming the glucose metabolism of cancer cells. Preferential expression of PKM2 is primarily driven by alternative splicing, which is coordinated by a group of splicing factors including heterogeneous nuclear ribonucleoprotein (hnRNP)A1, hnRNPA2 and RNA binding motif containing. However, the underlying molecular mechanisms associated with cancer cell expression of PKM2, instead of PKM1, remain unknown. The mRNA levels of PKM isoform and glucose metabolism were analyzed in CRC cells. The results of the present study indicated that S6 kinase 2 (S6K2) promotes glycolysis and growth of CRC cells by regulating alternative splicing of the PKM gene. In addition, chromatin immunoprecipitation assay indicated that S6K2 phosphorylation of Ser6 of hnRNPA1 facilitated hnRNPA1 binding to the splicing site of the PKM gene. As a result, cancer cells preferentially expressed the PKM2 isoform, instead of the PKM1 isoform. Furthermore, Cox regression analysis demonstrated that the phosphorylation of Ser6 of hnRNPA1 was a predictor of poor prognosis for patients with CRC. Therefore, the results of the present study revealed that the phosphorylation of Ser6 in hnRNPA1 by S6K2 was a novel mechanism underlying glucose metabolic reprogramming, and suggested that S6K2 is a potential therapeutic target for CRC treatment. [ABSTRACT FROM AUTHOR]

This paper presents analytical study of a non-uniform shallow arch under a central concentrated load. The non-uniformity is characterized by three constant stiffness regions. The least potential energy principle is used to obtain the equilibrium equations. The anti-symmetric buckling axial compression and buckling modes are shown to be identical with those of Euler-Bernoulli beam. The initial imperfection effect is also investigated theoretically and a parametric study on the different geometric parameters has been carried out on the snap-through symmetric buckling load and anti-symmetric buckling load. The comparison against the finite element analysis shows the accuracy of the theoretical model. We show that the stiffer center case is always economically better than the stiffer end case. The two limiting cases with largest degree of non-uniformity are analytically analyzed by using the augmented potential energy with the Lagrangian multiplier. The closed-form condition for the occurrence of symmetric snap-through buckling is presented for one limiting case. This paper serves to enhance the understanding of the effect of the non-uniformity of shallow arch on its load carrying capacity. [ABSTRACT FROM AUTHOR]

Background: Alfalfa (Medicago sativa) is the most extensively cultivated forage legume in the world, and salinity stress is the most problematic environmental factors limiting alfalfa production. To evaluate alfalfa tissue variations in response to salt stress, comparative physiological and proteomic analyses were made of salt responses in the roots and shoots of the alfalfa. Method: A two-dimensional gel electrophoresis (2-DE)-based proteomic technique was employed to identify the differentially abundant proteins (DAPs) from salt-treated alfalfa roots and shoots of the salt tolerance cultivars Zhongmu No 1 cultivar, which was subjected to a range of salt stress concentrations for 9 days. In parallel, REL, MAD and H2O2 contents, and the activities of antioxidant enzymes of shoots and roots were determinand. Result: Twenty-seven spots in the shoots and 36 spots in the roots that exhibited showed significant abundance variations were identified by MALDI-TOF-TOF MS. These DAPs are mainly involved in the biological processes of photosynthesis, stress and defense, carbohydrate and energy metabolism, second metabolism, protein metabolism, transcriptional regulation, cell wall and cytoskeleton metabolism, ion transpor, signal transduction. In parallel, physiological data were correlated well with our proteomic results. It is worth emphasizing that some novel salt-responsive proteins were identified, such as CP12, pathogenesis-related protein 2, harvest-induced protein, isoliquiritigenin 2'-O-methyltransferase. qRT-PCR was used to study the gene expression levels of the four above-mentioned proteins; four patterns are consistent with those of induced protein. Conclusion: The primary mechanisms underlying the ability of alfalfa seedlings to tolerate salt stress were photosynthesis, detoxifying and antioxidant, secondary metabolism, and ion transport. And it also suggests that the different tissues responded to salt-stress in different ways. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a B-cell neoplasm with a high incidence of relapse. Bortezomib has been extensively studied for the maintenance treatment of MM. Here, we carried out a meta-analysis to determine the efficacy and safety of maintenance therapy with bortezomib. We searched for clinical trials in PubMed (Medline), Embase (OVID), and the Cochrane Library. Two randomized controlled trials (RCTs) enrolling a total of 1338 patients were included. Bortezomib maintenance statistically significantly improved both progression-free survival (PFS) (hazard ratio (HR) 0.67, 95% confidence interval (CI) = 0.51 to 0.87, P=0.003) and overall survival (OS) (HR = 0.75 therapy, 95% CI = 0.63 to 0.89, P=0.001) more than did non-bortezomib maintenance therapy. Our analysis revealed higher incidence of neutropenia (risks ratios (RR) = 1.39; 95% CI = 1.08 to 1.79), peripheral neuropathy (PN) (RR = 2.23; 95% CI = 1.38 to 3.61, P=0.001), and cardiologic events (RR = 1.91; 95% CI = 1.12 to 3.28, P=0.02) in patients with bortezomib maintenance therapy. Our meta-analysis demonstrates OS and PFS benefits of bortezomib maintenance therapy in patients with newly diagnosed MM. However, the therapy is associated with increased risk of adverse events. Additionally, more RCTs are needed for better understanding and determination of optimal bortezomib maintenance therapy in MM. [ABSTRACT FROM AUTHOR]

Using interview data from a medium Chinese city collected in Dec. 2015, this paper assesses the impact of Xi Jinping's anti-corruption campaign on the Chinese public's perception of corruption and relatedly, regime legitimacy. We argue that the campaign has mixed effects: it has had more effects in cracking down on high-level officials and the “three public consumptions,” but it has had less effects in controlling the types of corruption that affect citizens' lives more directly. Thus the campaign has helped to enhance public satisfaction with anti-corruption at the national level, but less so at the local level or with anti-corruption mechanisms in general. The latter trends will continue to affect public perception of corruption and its associated impact on regime legitimacy, but serious damages will be mitigated by perceived anti-corruption success at the national level and expectations for trickle-down effects on anti-corruption at the local level. [ABSTRACT FROM AUTHOR]

8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) is one of the most common DNA lesions resulting from reactive oxygen species and ionizing radiation, and is involved in mutagenesis, carcinogenesis, and cell death. Notably, 8-oxodGuo is more reactive toward singlet (a¹Δg) O2 than the undamaged guanosine, and the lesions arising from the secondary oxidation of 8-oxodGuo are more mutagenic. Herein the ¹O2 oxidation of free base 8-oxoguanine (8-oxoG) was investigated at different initial conditions including protonated [8-oxoG + H]+, deprotonated [8-oxoG - H]-, and their monohydrates. Experiment was carried out on a guided-ion beam scattering tandem mass spectrometer. Measurements include the effects of collision energy (Ecol) on reaction cross sections over a center-of-mass Ecol range from 0.1 to 0.5 eV. The aim of this study is to quantitatively probe the sensitivity of the early stage of 8-oxoG oxidation to ionization and hydration. Density functional theory and Rice-Ramsperger-Kassel-Marcus calculations were performed to identify the intermediates and the products along reaction pathways and locate accessible reaction potential energy surfaces, and to rationalize reaction outcomes from energetic and kinetic points of view. No product was observed for the reaction of [8-oxoG + H]+·W0,1 (W = H2O) because insurmountable barriers block the addition of ¹O2 to reactant ions. Neither was [8-oxoG - H]- reactive with ¹O2, in this case due to the rapid decay of transient intermediates to starting reactants. However, the nonreactivity of [8-oxoG - H]- was inverted by hydration; as a result, 4,5-dioxetane of [8-oxoG - H]- was captured as the main oxidation product. Reaction cross section for [8-oxoG - H]-·W + ¹O2 decreases with increasing Ecol and becomes negligible above 0.3 eV, indicating that the reaction is exothermic and has no barriers above reactants. The contrasting oxidation behaviors of [8-oxoG + H]+·W0,1 and [8-oxoG - H]-·W0,1, which are relevant to the pH dependence of 8-oxoG oxidation in solution, are interpreted in terms of different ¹O2 addition pathways. [ABSTRACT FROM AUTHOR]

Receptor interacting protein kinase 2 (RIPK2) is involved in a variety of signaling pathway to produce a series of inflammatory cytokines in response to a diverse of bacterial, viral and protozoal pathogens. However, the underlying regulating of RIPK2 remain unknown. Transcriptome alterations in chicken HD11 cells following RIPK2 overexpression or silencing by shRNA were analyzed by next-generation sequencing. Both overexpression and knockdown of the RIPK2 gene caused wide-spread changes in gene expression in chicken HD11 cells. Differentially expressed genes (DEGs) caused by altered RIPK2 gene expression were associated with multiple biological processes linked with biological regulation, response to stimulus, cell communication, and signal transduction etc. KEGG analysis revealed that many of the DEGs were enriched in VEGF signaling pathway, ECM-receptor interaction, Focal adhesion, TGF-beta signaling pathway etc. Moreover, we show that initiation genes, TGFB1 and TGFB3, in the TGF-beta signaling pathway are biological targets regulated by RIPK2 in chicken HD11 cells. This is the first transcriptome-wide study in which RIPK2-regulated genes in chicken cells have been screened. Our findings elucidate the molecular events associated with RIPK2 in chicken HD11 cells. [ABSTRACT FROM AUTHOR]

In two studies, people were reluctant to trade items they own, but glad to accept upgrades with identical end states. The framing of the transaction makes a difference. A mediational analysis suggests that the relationship between the frame of the transaction and measures of value (willingness to accept, WTA) depends on perceived losses. Losses are perceived as greater when the transaction is a trade than as an upgrade. We manipulated perceptions of loss across descriptions of transactions and found that, when the difference in perceptions of losses with trades versus upgrades was large, framing effects were strong. But when the difference was small, framing effects disappeared. These framing effects with identical end states influence WTA because trades are associated with perceived losses, while upgrades are associated with perceived costs. [ABSTRACT FROM AUTHOR]

Background: There is a high mortality in infants with right atrial isomerism (RAI). However, less is known about outcome in older children with RAI. This study sought to evaluate those patients with RAI who survived older than 3 years of age without surgical intervention. Results: A total of 33 consecutive patients (20 males) were enrolled in the study, mean age 6 years (range 3-32). None of the patients had surgical intervention for the RAI before age 3. Cardiac abnormalities include altered cardiac position (39 %), atrioventricular valve anomaly (87 %), single or functional single ventricle (55 %), pulmonary/subpulmonary obstruction (97 %), abnormal origin of the aorta (100 %), bilateral superior vena cava (67 %), and anomalous pulmonary venous drainage (66 %). Surgical intervention was performed after 3 years of age in 20 patients (61 %). None of them planned or had biventricular repair performed. 10 patients underwent the total cavopulmonary connection procedure, including four (40 %) who had atrioventricular valve (AVV) repair at the same time [all with common atrioventricular valve (CAVV)]. One patient died the day after the operation. A total of 69 % of patients with a CAVV had moderate or severe regurgitation, while 27 % with a single atrioventricular valve had moderate or severe regurgitation. Conclusion: Patients with RAI who have survived to early childhood without surgical intervention have complex cardiac abnormalities. Survival after single stage total cavopulmonary connection is good but AVV repair is common. [ABSTRACT FROM AUTHOR]

Minimal residual disease (MRD) is one of the causes of leukemia recurrence. Previously, we developed anti-CD10 mAb conjugated to muramyl dipeptide immunoconjugate (MDP-Ab) for immune enhancement. The present study aimed to investigate anti-leukemia effect of MDP-Ab administered via different methods in leukemia ectopic graft nude mouse model. BALB/c nude mice were injected with Nalm-6 cells subcutaneously to establish leukemia xenografts in nude mice as a model. MDP-Ab or/and human lymphocytes (LYM) was injected into different sites of the nude mice. Immunohistochemistry staining of CDs in the bone marrow, liver and spleen was performed. IFN-γ was detected by ELISA. We detected the metastasis of leukemia cells to the liver, spleen and bone marrow in nude mouse leukemia model. MDP-Ab and LYM inhibited the growth of tumors, and simultaneous injection of MDP-Ab and LYM into the tumor inhibited the growth of tumors. IFN-γ levels in MDP-Ab (ca) + h-LYM (ca) group, MDP-Ab (ca) + h-LYM (ip) group, MDP-Ab (iv) + h-LYM (ip) group and PBS (ca) + h-LYM (ca) group were significantly higher than those in control group, while IFN-γ level in MDP-Ab (ca) + h-LYM (ca) group was the highest. Moreover, MDP-Ab and h-LYM promoted the expression of hCD4 and hCD8, with the highest expression in MDP-Ab (ca) + h-LYM (ca) group. In conclusion, MDP-Ab effectively promoted the production of IFN-γ, enhanced the antitumor immunity of T lymphocytes and inhibited leukemia. [ABSTRACT FROM AUTHOR]

The potential weight of accumulated snow on the roof of a structure has long been an important consideration in structure design. However, the historical approach of modeling the weight of snow on structures is incompatible for structures with surfaces and geometry where snow is expected to slide off of the structure, such as standalone solar panels. This paper proposes a "storm-level" adaptation of previous structure-related snow studies that is designed to estimate short-term, rather than season-long, accumulations of the snow water equivalent or snow load. One key development associated with this paper includes a climate-driven random forests model to impute missing snow water equivalent values at stations that measure only snow depth in order to produce continuous snow load records. Additionally, the paper compares six different approaches of extreme value estimation on short-term snow accumulations. The results of this study indicate that, when considering the 50-year mean recurrence interval (MRI) for shortterm snow accumulations across different weather station types, the traditional block maxima approach, the mean-adjusted quantile method with a gamma distribution approach, and the peak over threshold Bayesian approach tend to most often provide MRI estimates near the median of all six approaches considered in this study. Further, this paper also shows, via bootstrap simulation, that the peak over threshold extreme value estimation using automatic threshold selection approaches tend to have higher variance compared to the other approaches considered. The results suggest that there is no one-size-fits-all option for extreme value estimation of shortterm snow accumulations, but highlights the potential value from integrating multiple extreme value estimation approaches. [ABSTRACT FROM AUTHOR]

Animal development and physiology depend on beneficial interactions with microbial symbionts. In many cases, the microbial symbionts are horizontally transmitted among hosts, thereby making the acquisition of these microbes from the environment an important event within the life history of each host. The light organ symbiosis established between the Hawaiian squid Euprymna scolopes and the bioluminescent bacterium Vibrio fischeri is a model system for examining how hosts acquire horizontally transmitted microbial symbionts. Recent studies have revealed that the light organ of wild-caught E. scolopes squid contains polyclonal populations of V. fischeri bacteria; however, the function and development of such strain diversity in the symbiosis are unknown. Here, we report our phenotypic and phylogenetic characterizations of FQ-A001, which is a V. fischeri strain isolated directly from the light organ of an E. scolopes individual. Relative to the type strain ES114, FQ-A001 exhibits similar growth in rich medium but displays increased bioluminescence and decreased motility in soft agar. FQ-A001 outcompetes ES114 in colonizing the crypt spaces of the light organs. Remarkably, we find that animals cocolonized with FQ-A001 and ES114 harbor singly colonized crypts, in contrast to the cocolonized crypts observed from competition experiments involving single genotypes. The results with our two-strain system suggest that strain diversity within the squid light organ is a consequence of diversity in the single-strain colonization of individual crypt spaces. [ABSTRACT FROM AUTHOR]

Background: Extensive-disease small-cell lung cancer (ED-SCLC) is characterized by rapid progression and relapse, despite high initial response rates to chemotherapy. The primary objective of this trial was to demonstrate the non-inferiority of amrubicin and cisplatin (AP) combination therapy compared with the standard first-line regimen of etoposide and cisplatin (EP) for previously untreated ED-SCLC in a Chinese population. When non-inferiority was verified, the objective was switched from non-inferiority to superiority.Methods: From June 2008 to July 2010, 300 patients were enrolled and randomly assigned at a 1:1 ratio to AP and EP groups. AP-treated patients received cisplatin (60 mg/m(2), day 1) and amrubicin (40 mg/m(2), days 1-3) once every 21 days. EP-treated patients received cisplatin (80 mg/m(2), day 1) and etoposide (100 mg/m(2), days 1-3) once every 21 days. Treatment was continued for four to six cycles, except in cases of progressive disease or toxicity, and patient refusal.Results: Median overall survival (OS) for AP vs. EP treatment was 11.8 vs. 10.3 months (p = 0.08), respectively, demonstrating non-inferiority of AP to EP (AP group: 95% confidence interval for hazard ratio 0.63-1.03 months). Median progression-free survival and overall response rates for AP vs. EP groups were 6.8 vs. 5.7 months (p = 0.35) and 69.8% vs. 57.3%, respectively. Drug-related adverse events in both groups were similar, with neutropenia being the most frequent (AP 54.4%; EP 44.0%). Leukopenia, pyrexia, and fatigue were more prevalent in the AP group, but all were clinically reversible and manageable.Conclusions: AP therapy demonstrated non-inferiority to EP therapy, prolonging OS for 1.5 months, but this difference was not statistically significant; thus we propose AP as a promising treatment option for ED-SCLC in China.Trial Registration: This trial was registered on 10 April 2008 (ClinicalTrials.gov NCT00660504). [ABSTRACT FROM AUTHOR]

The present study aimed to investigate whether grape seed proanthocyanidin extract (GSPE) has a protective effect on diabetic retinal function. A total of 30 Wistar rats were randomly divided into three equal groups, including the control, diabetic and GSPE-treated diabetic groups. Retinal tissue was harvested and subsequently stained with hematoxylin and eosin. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and methane dicarboxylic aldehyde (MDA) levels were evaluated using respective assay kits; whereas nuclear erythroid 2-related factor 2 (Nrf2) and heme oxygenase (HO)-1 expression levels were assessed by immunohistochemical and western blot analysis. Cell apoptosis in the retina was determined using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling method. The results showed that the structure of the retina was damaged in diabetic rats, as compared with the control rats. Notably, the structure of the retina improved in the GSPE-treated diabetic group, as compared with the diabetic group. SOD and GSH-Px activities were significantly increased in the retina of rats in the GSPE-treated diabetic group, as compared with the diabetic group (P=0.011 and P=0.001, respectively). Furthermore, a significant reduction in MDA was detected (P=0.013) and the expression levels of Nrf2 and HO-1 in the bladders of rats in the GSPE-treated diabetic group were significantly increased, as compared with the diabetic group (P=0.038 and P=0.043, respectively). Apoptosis of retinal cells was significantly increased in the diabetic group, as compared with the control group (P<0.001); a significant reduction was also detected in the GSPE-treated diabetic group, as compared with the diabetic group (P=0.014). These results demonstrate that GSPE administration may protect the retina against hyperglycemic damage, possibly by ameliorating oxidative stress-mediated injury via the activation of the Nrf2 pathway. [ABSTRACT FROM AUTHOR]

In this study, we combine the fuzzy customer information problem with the multicommodity multimodal routing with schedule-based services which was explored in our previous study [1]. The fuzzy characteristics of the customer information are embodied in the demanded volumes of the multiple commodities and the time windows of their due dates. When the schedule-based services are considered in the routing, schedule constraints emerge because the operations of block container trains should follow their predetermined schedules. This will restrict the routes selection from space-time feasibility. To solve this combinatorial optimization problem, we first build a fuzzy chance-constrained nonlinear programming model based on fuzzy possibility theory. We then use a crisp equivalent method and a linearization method to transform the proposed model into the classical linear programming model that can be effectively solved by the standard mathematical programming software. Finally, a numerical case is presented to demonstrate the feasibility of the proposed method. The sensitivity of the best solution with respect to the values of the confidence levels is also examined. [ABSTRACT FROM AUTHOR]

Background: FAS/FASL promoter variants are considered in altering transcriptional activity of those genes and consequently alter regulation of cell death. However, no studies have investigated whether tumor sites contribute to the association between FAS/FASL polymorphisms and risk for second primary malignancy (SPM).Method: In this study, FAS670 A > G, FAS1377 G > A, FASL124 A > G, and FASL844C > T polymorphisms were genotyped in 752 OPC and 777 non-OPC patients. Both univariate and multivariable cox proportional hazard models were used to assess the associations.Results: The univariate and multivariable analyses showed that patients with index OPC and FASL844 CT/TT genotype had significantly increased risk of SPM (cHR, 2.5; 95% CI, 1.1-5.8, P = 0.043 and aHR, 2.7; 95% CI, 1.2-6.0, P = 0.032) compared with those with FASL844 CC genotype as the reference group, while index non-OPC patients with FAS670 AG/GG and FasL844 CT/TT genotypes had significantly increased risk of SPM (cHR, 2.2 and 1.8; 95% CI, 1.2-5.7 and 1.1-3.2; and P = 0.04 and 0.041, respectively and aHR, 2.4 and 1.7; 95% CI, 1.1-5.1 and 1.0-3.0; and P = 0.043 and 0.049, respectively) compared with their corresponding AA and CC genotypes . Moreover, patients carrying more FAS/FASL variants significantly increased risk of SPM among index non-OPC patients. The stratified analysis showed that smoking status differently modified the associations between FAS/FASL polymorphisms and risk of SPM among index non-OPC from OPC patients.Conclusion: These results suggested that FAS/FASL polymorphisms might significantly modify SPM risk among patients with SCCHN in a tumor site-specific manner. [ABSTRACT FROM AUTHOR]

Background: Cycloartane triterpenoids exhibited anticancer efects. This study aims to identify any potential novel anticancer cycloartane triterpenoids from Cimicifuga foetida L. rhizome (Sheng ma) and the mode of actions. Methods: Cycloartane triterpenoids were isolated from the C. foetida rhizome by a series of column chromatography and identiied by IR, MS and NMR. Their anticancer efects on several human cancer cell lines, MCF-7, HepG2, HepG2/ ADM, HeLa, and PC3, and normal human mammary epithelial cells MCF10A were investigated by colony formation and MTT assays. Morphological analysis of apoptosis induction was performed by acridine orange/ethidium bromide dual-staining and Hoechst 33258 nuclear staining. The cell-cycle proile and annexin V staining were evaluated by low cytometry. Apoptosis were investigated by measuring changes in mitochondrial membrane potential and analyzing expression of cell cycle- and apoptosis-related proteins in MCF-7 cells by Western blotting. Results: A novel cycloartane triterpenoid, 25-O-acetyl-7,8-didehydrocimigenol-3-O-β-D-(2-acetyl)xylopyranoside (ADHC-AXpn), together with the known 7,8-didehydrocimigenol-3-O-β-d-xylopyranoside (DHC-Xpn) were isolated. MCF-7 growth was signiicantly inhibited by ADHC-AXpn in a dose- and time-dependent manner (IC50 : 27.81 µM at 48 h; P = 0.004 vs. control at 25 µM for 48 h treatment), and ADHC-AXpn was selectively cytotoxic for cancerous cells (MCF-7, HepG2/ADM, HepG2 and HELA cells) based on its higher IC50 values for normal cells MCF10A (IC50 : 78.63 µM at 48 h) than for tumor cells. In MCF-7 cells, ADHC-AXpn induced G2/M cell cycle arrest by mediating cyclin-B1, and CDK1 and its phosphorylation; and induced apoptosis through the mitochondrial-mediated apoptotic pathway, with inhibition of Akt activation. As ADHC-AXpn suppressed phosphorylation of ERK1/2, Raf and Akt proteins in MCF-7 cells, its apoptotic efect might be associated with Raf/MEK/ERK signaling and Akt activation. Conclusions: ADHC-AXpn signiicantly suppressed the growth of MCF-7 cells, induced mitochondrial apoptosis and cell-cycle arrest, and inhibited Raf/MEK/ERK signaling pathway and Akt phosphorylation. [ABSTRACT FROM AUTHOR]

Objective: Human murine double minute 2 protein (MDM2) is mainly a negative regulator of p53 tumor suppressor pathway. We aimed to investigate the association between MDM2 SNP309 polymorphism and bladder cancer risk. Methods: A total of 535 bladder cancer patients and 649 health controls were recruited for our study. MDM2 SNP309 T>G polymorphism was genotyped by polymerase chain reaction-ligase detection reaction method. Logistic regression was used to analyze the relationship between the genotype and susceptibility of bladder cancer. Kaplan–Meier estimates and log-rank test were obtained to analyze the association between the genotype and risk of recrudesce in nonmuscleinvasive bladder cancer patients. A multivariable Cox proportional hazards model was fitted to identify independent prognostic factors. To further investigate the association, we conducted a meta-analysis including six studies. Results: The frequency of the MDM2 SNP309 T>G polymorphism showed no significant difference between cases and controls (all P>0.05). In the stratification analysis, the results showed that G allele carriers were prone to have a significant decrease in risk of low-grade bladder cancer (adjusted odds ratio: 0.613, 95% confidence interval: 0.427–0.881), and G variant was associated with a significantly reduced risk of recurrence in nonmuscle-invasive bladder cancer patients with or without chemotherapy (P<0.05). The results of the meta-analysis showed that G allele and GG genotype of MDM2 SNP309 polymorphism were significantly associated with increased risk of bladder cancer in Caucasians (both P<0.05), and no association was observed in total populations and Asians (P>0.05). Conclusion: MDM2 SNP309 T>G polymorphism has no influence on bladder cancer risk in Asians, but this single nucleotide polymorphism may be associated with genetic susceptibility of bladder cancer among Caucasians. [ABSTRACT FROM AUTHOR]