Truncated O-Glycan-Bearing MUC16 Enhances Pancreatic Cancer Cells Aggressiveness via α4β1 Integrin Complexes and FAK Signaling

Elevated levels of Mucin-16 (MUC16) in conjunction with a high expression of truncated O-glycans is implicated in playing crucial roles in the malignancy of pancreatic ductal adenocarcinoma (PDAC). However, the mechanisms by which such aberrant glycoforms present on MUC16 itself promote an increased disease burden in PDAC are yet to be elucidated. This study demonstrates that the CRISPR/Cas9-mediated genetic deletion of MUC16 in PDAC cells decreases tumor cell migration. We found that MUC16 enhances tumor malignancy by activating the integrin-linked kinase and focal adhesion kinase (ILK/FAK)-signaling axis. These findings are especially noteworthy in truncated O-glycan (Tn and STn antigen)-expressing PDAC cells. Activation of these oncogenic-signaling pathways resulted in part from interactions between MUC16 and integrin complexes (α4β1), which showed a stronger association with aberrant glycoforms of MUC16. Using a monoclonal antibody to functionally hinder MUC16 significantly reduced the migratory cascades in our model. Together, these findings suggest that truncated O-glycan containing MUC16 exacerbates malignancy in PDAC by activating FAK signaling through specific interactions with α4 and β1 integrin complexes on cancer cell membranes. Targeting these aberrant glycoforms of MUC16 can aid in the development of a novel platform to study and treat metastatic pancreatic cancer.     

Pairwise testing for software product lines: comparison of two approaches

Software Product Lines (SPL) are difficult to validate due to combinatorics induced by variability, which in turn leads to combinatorial explosion of the number of derivable products. Exhaustive testing in such a large products space is hardly feasible. Hence, one possible option is to test SPLs by generating test configurations that cover all possible t feature interactions (t-wise). It dramatically reduces the number of test products while ensuring reasonable SPL coverage. In this paper, we report our experience on applying t-wise techniques for SPL with two independent toolsets developed by the authors. One focuses on generality and splits the generation problem according to strategies. The other emphasizes providing efficient generation. To evaluate the respective merits of the approaches, measures such as the number of generated test configurations and the similarity between them are provided. By applying these measures, we were able to derive useful insights for pairwise and t-wise testing of product lines.     

钻进了野区的路西法

大家在筛选录像的时候会发现，每一场DOTA2比赛都有自己的等级，分为普通、高、非常高三种。比赛的等级是由每个人的Matchmarkingranking数值所决定的，我们简称其为MMR值，与天梯积分有点像。     

Verification of the applicability of lattice model to concrete fracture by AE study

Notched three-point bend specimens (TPB) were tested under crack mouth opening displacement (CMOD) control at a rate of 0.0004 mm/s and the entire fracture process was simulated using a regular triangular two-dimensional lattice network only over the expected fracture process zone width. The rest of the beam specimen was discretised by a coarse triangular finite element mesh. The discrete grain structure of the concrete was generated assuming the grains to be spherical. The load versus CMOD plots thus simulated agreed reasonably well with the experimental results. Moreover, acoustic emission (AE) hits were recorded during the test and compared with the number of fractured lattice elements. It was found that the cumulative AE hits correlated well with the cumulative fractured lattice elements at all load levels thus providing a useful means for predicting when the micro-cracks form during the fracturing process, both in the pre-peak and in the post-peak regimes.     

Structural development and magnetic phenomenon in Zn–Cr–Fe multi oxide nano-crystals

The Cr³⁺ ions doped multi-oxide ZnFe_2−xCr_xO₄ ferrite nanoparticles have been synthesized by chemical co-precipitation method. Site occupancies of Zn²⁺, Cr³⁺ and Fe³⁺ ions were analyzed using X-ray diffraction data and Buerger's method. The effect of the constituent phase variation on the magnetic hysteresis behavior was examined by saturation magnetization which decreases with the increase in Cr³⁺ content in place of Fe³⁺ ions at octahedral B-site. Typical blocking temperature (T_B) around 90 K was observed by zero field cooling and field cooling magnetization study. Room temperature Mössbauer spectra show two paramagnetic doublets (tetrahedral and octahedral sites). The isomer shifts of both doublets decrease whereas quadrupole splitting and relative area of tetrahedral A-site increases with increasing Cr³⁺ substitution. The dielectric constant (measured on compositions x=0, 0.4, 0.8 and 1.0) increases when the temperature increases as in the semiconductor. This behavior is attributed to the hopping of electrons between Fe²⁺ and Fe³⁺ ions with a thermal activation.     

Carboxymethyl guar: Its synthesis and macromolecular characterization

Guar gum was partially carboxymethylated by the reaction of the base polysaccharide with the sodium salt of monochloroacetic acid in presence of sodium hydroxide. The resulting products (carboxymethyl guar with different degrees of substitution) were characterized by a variety of material characterization techniques, such as intrinsic viscosity measurement, determination of molecular weight, elemental analysis, thermal analysis, ¹³C‐NMR spectra, and Fourier transform infrared analysis. Various grades of carboxymethyl guar gum, which were synthesized in the laboratory, were studied for their suitability as flocculants and viscosifiers. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Effects of Clinorotation on Growth and Chlorophyll Content of Rice Seeds

Microgravity, as a different environment, has been shown to affect plant growth and development (Sievers et al. 1996; Sack 1997). In the present study, effects of slow clinorotation (2 rpm) on growth and chlorophyll content in rice (variety: PRH-10) seedlings were investigated. Rice seeds were clinorotated continuously for 3, 5 and 7 days under ambient conditions. Root and shoot lengths and weights of rice seedlings were measured on the third, fifth and seventh day. Chlorophyll was extracted using N, N-Dimethylformamide (DMF). Absorption and fluorescence spectra of chlorophyll were recorded. Chlorophyll a, chlorophyll b and total chlorophyll contents were calculated from absorption spectra using Arnon’s method. Results showed an increase in root and shoot lengths in clinorotated samples. Similar results were obtained for root and shoot weights. Absorption spectra of chlorophyll showed no shift in the absorption peaks. Chlorophyll content was increased in clinorotated samples as compared to the controls. Interestingly, the difference between chlorophyll content in control and clinorotated samples decreased as the number of days of clinorotation increased. Chlorophyll a/b ratio was lowered in clinorotated samples as compared to the controls. These results suggest that slow clinorotation (2 rpm) affects plant growth and chlorophyll content in rice seedlings.     

Changes in volatile composition during fruit development and ripening of ‘Alphonso’ mango

BACKGROUND: Volatile blends of five developing and five ripening stages of mango (Mangifera indica L. cv. Alphonso) were investigated along with those of flowers and leaves. Raw and ripe fruits of cv. Sabja were also used for comparison. RESULTS: A total of 55 volatiles belonging to various chemical classes such as aldehydes, alcohols, mono‐ and sesquiterpene hydrocarbons, lactones and furanones were identified. In all Alphonso tissues monoterpenes quantitatively dominated, with 57–99% contribution; in particular, (Z)‐ocimene was found in the highest amount. Ripeness was characterized by the de novo appearance of lactones and furanones in the blend of monoterpenes. Sabja was distinguished by the abundance of monoterpene hydrocarbons in the raw fruit, and that of sesquiterpene hydrocarbons and their derivatives in the ripe stage. CONCLUSION: Various stages of the Alphonso fruit during transition from flower to ripe fruit are characterized by unique volatile signatures that are distinguished from each other by the qualitative and quantitative appearance of different volatile compounds. Thus volatiles can be highly informative markers while studying the development and ripening of mango. Copyright © 2009 Society of Chemical Industry     

Use of cellular confinement for improved railway performance on soft subgrades

Due to extensive right-of-way, railroads are inevitably subject to poor subgrade conditions and interrupted service for significant maintenance due to excessive deformations and loss of track geometry. Geocell confinement presents itself as a possible solution for improving performance of ballasted railroad embankments over weak subgrade. To investigate the efficacy of geocell confinement on ballasted railway embankments, a set of well-instrumented, large-scale cyclic plate loading tests and numerical simulations were performed on geocell-confined ballast overlaying a weak subgrade material. The agreement of results from tests and simulations served as a basis for simulating practical track geometry and performance for various geocell configurations and subgrades using three-dimensional (3D) finite element (FE) analyses. The study showed that geocell reinforcement significantly decreased track settlement, decreased subgrade deformations with lower and uniform distribution of vertical stresses on subgrade and inhibited lateral deformation and serviceability under cyclic loading. These results demonstrate that geocell confinement can be an effective alternative to subsurface improvement or shorter maintenance cycles, particularly on weak subgrades.