Proteomic analysis of colorectal cancer metastasis:stathmin-1 revealed as a player in cancer cell migration and prognostic marker

Metastasis accounts largely for the high mortality rate of colorectal cancer (CRC) patients. In this study, we performed comparative proteome analysis of primary CRC cell lines HCT-116 and its metastatic derivative E1 using 2-D DIGE. We identified 74 differentially expressed proteins, many of which function in transcription, translation, angiogenesis signal transduction, or cytoskeletal remodeling pathways, which are indispensable cellular processes involved in the metastatic cascade. Among these proteins, stathmin-1 (STMN1) was found to be highly up-regulated in E1 as compared to HCT-116 and was thus selected for further functional studies. Our results showed that perturbations in STMN1 levels resulted in significant changes in cell migration, invasion, adhesion, and colony formation. We further showed that the differential expression of STMN1 correlated with the cells' metastatic potential in other paradigms of CRC models. Using immunohistochemistry, we also showed that STMN1 was highly expressed in colorectal primary tumors and metastatic tissues as compared to the adjacent normal colorectal tissues. Furthermore, we also showed via tissue microarray analyses of 324 CRC tissues and Kaplan-Meier survival plot that CRC patients with higher expression of STMN1 have poorer prognosis.

PTGS2 (Cyclooxygenase-2) expression and survival among colorectal cancer patients: A systematic review

Background: Studies have examined whether tumor expression of PTGS2 (also known as COX-2), an enzyme inhibited by nonsteroidal anti-inflammatory drugs such as aspirin, is associated with prognosis in patients with colorectal cancer. However, results to date have been mixed. Methods: Using terms for PTGS2 and colorectal cancer, the Medline, Embase, and Web of Science databases were systematically searched for studies published, in any language, until December 2011. Random effects meta-analyses were used to calculate pooled HRs [95% confidence intervals (CI)] for the association between PTGS2 expression and tumor recurrence, colorectal cancer-specific survival, and overall survival. Results: In total, 29 studies, which had prognostic data on 5,648 patients, met the inclusion criteria. PTGS2- positive patients were at an increased risk of tumor recurrence (n = 9 studies; HR, 2.79; 95% CI, 1.76-4.41; P <0.001) and had poorer colorectal cancer-specific survival (n = 7; HR, 1.36; 95% CI, 1.02-1.82; P = 0.04). However, there was funnel plot asymmetry, possibly due to publication bias, for the association with cancerspecific survival but less so for recurrence. PTGS2 expression was not associated with overall survival [(n= 16; pooled unadjusted HR, 1.30; 95% CI, 0.94-1.79; P=0.11) and (n=9; pooled adjusted HR, 1.02; 95% CI, 0.72-1.45; P = 0.91)]. Conclusions: PTGS2 expression was associated with an increased risk of tumor recurrence and poorer colorectal cancer-specific survival but not overall survival among patients with colorectal cancer. However, confounding by tumor characteristics such as tumor stage seems likely. Impact: There is insufficient evidence to recommend PTGS2 expression as a prognostic marker in patients with colorectal cancer. Furthermore, studies providing adjusted results are required. © 2013 AACR.

Comportamento flessionale di nodi esterni in calcestruzzo fibrorinforzato

SOMMARIO – Si presenta un macro modello di tipo reticolare in grado di riprodurre il comportamento in presenza di taglio e momento di nodi esterni trave-colonna di telai in calcestruzzo fibrorinforzato con fibre di acciaio
uncinato ed ordinario. Il caricamento del sistema è di tipo monotono come nel caso dell’analisi di pushover. Il modello considera la presenza di armature orizzontali e verticali della regione nodale e tiene in conto delle modalità
di rottura legate allo snervamento delle barre e allo schiacciamento delle regioni compresse in regime di sforzi pluriassiali. Il modello include le deformazioni flessionali della trave e della colonna in presenza di sforzo normale costante e restituisce la risposta del sistema colonna-nodo-trave (sub-assembralggio) tramite le curve carico-freccia all’estremità della semitrave. Per i singoli costituenti (trave, colonna e nodo) si è considerata la prima fessurazione, lo snervamento e lo schiacciamento delle regioni compresse e si sono fornite precise indicazioni sulla sequenza degli eventi che come è noto sono di fondamentale importanza per lo sviluppo di un progetto plastico che rispetti la gerarchia delle resistenze. Con l’uso del modello il controllo della gerarchia delle resistenze avviene a livello sezionale (lo snervamento delle barre deve avvenire prima dello schiacciamento delle regioni compresse) o di macro elemento (nella regione nodale lo snervamento delle staffe precede la crisi dei puntoni) e dell’intero elemento
sub-assemblaggio trave debole, colonna forte e nodo sovraresistente.
La risposta ottenuta con i modello proposto è in buon accordo con le risposte sperimentali disponibili in letteratura (almeno in termini di resistenza del sub-assemblaggio). Il modello è stato ulteriormente validato con analisi
numeriche agli elementi finiti condotte con il codice ATENA-2D. Le analisi numeriche sono state condotte utilizzando per il calcestruzzo fibroso adeguate leggi costitutive proposte dagli autori ed in grado di cogliere gli effetti
di softening e di resistenza residua a trazione legati alla presenza di fibre. Ulteriori sviluppi del modello saranno indirizzati a includere gli effetti di sfilamento delle barre d’armatura della trave e del conseguente degrado delle
tensioni d’aderenza per effetto di carichi monotonici e ciclici.

SUMMARY – A softened strut-and-tie macro model able to reproduce the flexural behavior of external beam-tocolumn joints with the presence of horizontal and vertical steel bars, including softening of compressed struts and yielding of main and secondary steel bars, is presented, to be used for the pushover analysis. The model proposed is able to calculate also the flexural response of fibrous reinforced concrete (FRC) beam-to-column sub-assemblages in term of a multilinear load-deflection curves. The model is able to take into account of the tensile behavior of main bars embedded in the surrounding concrete and of the softening of the compressed strut, the arrangement and percentage of the steel bars, the percentage and the geometry of steel fibers. First cracking, yielding of main steel and crushing of concrete were identified to determine the corresponding loads and displacement and to plot the simplified monotonic load-deflection curves of the sub-assemblages subjected in the column to constant vertical
load and at the tip of the beam to monotonically increasing lateral force. Through these load-delfection curves the component (beam, joint and column) that first collapse can be recognized and the capacity design can be verified.
The experimental results available in the literature are compared with the results obtained through the proposed model. Further, a validation of the proposed model is numerically made by using a non linear finite element program (ATENA-2D) able to analyze the flexural behavior of sub-assemblages.

Ecological Impacts of Alien Species: Quantification, Scope, Caveats, and Recommendations

Despite intensive research during the past decade on the effects of alien species, invasion science still lacks the capacity to accurately predict the impacts of those species and, therefore, to provide timely advice to managers on where limited resources should be allocated. This capacity has been limited partly by the context-dependent nature of ecological impacts, research highly skewed toward certain taxa and habitat types, and the lack of standardized methods for detecting and quantifying impacts. We review different strategies, including specific experimental and observational approaches, for detecting and quantifying the ecological impacts of alien species. These include a four-way experimental plot design for comparing impact studies of different organisms. Furthermore, we identify hypothesis-driven parameters that should be measured at invaded sites to maximize insights into the nature of the impact. We also present strategies for recognizing high-impact species. Our recommendations provide a foundation for developing systematic quantitative measurements to allow comparisons of impacts across alien species, sites, and time.

Community structure, diversity and spatial organization of enchytraeids in Mediterranean urban holm oak stands

There is a strong northern bias in Europe as regards enchytraeid community ecology, particularly in urban settings. We approached the enchytraeid assemblages of urban holm oak stands in Naples and Siena adopting a high intensity sampling that, for the first time in the Mediterranean climate zone, would ensure that the data collected be representative of the target populations. Structural parameters (diversity and evenness, biomass, size classes, aggregation) were compared across different spatial (regional, urban district, within habitat) and temporal scales (season and year). Species richness was found to change significantly only at regional scale; background data suggest that this may depend on the higher environmental heterogeneity occurring at Naples. Differences in size class structure were significant only on a seasonal scale and within either city separately. With one exception (Fridericia bulbosa s.s.), the patterns of spatial aggregation of the common species were fairly robust and the total range of patchiness was consistent with previous studies, despite the different sampling methodologies. The size of the sampling unit, the number of replicates per plot and the number of plots proposed in this study appear suitable to obviate the difficulties of evaluating Mediterranean enchytraeid communities.

Accuracy of LightCycler SeptiFast for the detection and identification of pathogens in the blood of patients with suspected sepsis: a systematic review and meta-analysis

Purpose: There is an urgent need to develop diagnostic tests to improve the detection of pathogens causing life-threatening infection (sepsis). SeptiFast is a CE-marked multi-pathogen real-time PCR system capable of detecting DNA sequences of bacteria and fungi present in blood samples within a few hours. We report here a systematic review and meta-analysis of diagnostic accuracy studies of SeptiFast in the setting of suspected sepsis.

Methods: A comprehensive search strategy was developed to identify studies that compared SeptiFast with blood culture in suspected sepsis. Methodological quality was assessed using QUADAS. Heterogeneity of studies was investigated using a coupled forest plot of sensitivity and specificity and a scatter plot in receiver operator characteristic space. Bivariate model method was used to estimate summary sensitivity and specificity.

Results: From 41 phase III diagnostic accuracy studies, summary sensitivity and specificity for SeptiFast compared with blood culture were 0.68 (95 % CI 0.63–0.73) and 0.86 (95 % CI 0.84–0.89) respectively. Study quality was judged to be variable with important deficiencies overall in design and reporting that could impact on derived diagnostic accuracy metrics.

Conclusions: SeptiFast appears to have higher specificity than sensitivity, but deficiencies in study quality are likely to render this body of work unreliable. Based on the evidence presented here, it remains difficult to make firm recommendations about the likely clinical utility of SeptiFast in the setting of suspected sepsis.

Kinetics study on thermal dissociation of levoglucosan during cellulose pyrolysis

(Chemical Equation Presented) The mechanisms and kinetics studies of the levoglucosan (LG) primary decomposition during cellulose pyrolysis have been carried out theoretically in this paper. Three decomposition mechanisms (C-O bond scission, C-C bond scission, and LG dehydration) including nine pathways and 16 elementary reactions were studied at the B3LYP/6-31 + G(D,P) level based on quantum mechanics. The variational transi-tion- state rate constants for every elementary reaction and every pathway were calculated within 298-1550 K. The first-order Arrhenius expressions for these 16 elementary reactions and nine pathways were suggested. It was concluded that computational method using transition state theory (TST) without tunneling correction gives good description for LG decomposition by comparing with the experimental result. With the temperature range of 667-1327 K, one dehydration pathway, with one water molecule composed of a hydrogen atom from C3 and a hydroxyl group from C2, is a preferred LG decomposition pathway by fitting well with the experimental results. The calculated Arrhenius plot of C-O bond scission mechanism is better agreed with the experimental Arrhenius plot than that of C-C bond scission. This C-O bond scission mechanism starts with breaking of C1-O5 and C6-O1 bonds with formation of CO molecule (C1-O1) simultaneously. C-C bond scission mechanism is the highest energetic barrier pathway for LG decomposition. © 2013 Elsevier Ltd. All rights reserved.

Photoelectrochemistry using quinone radical anions

The photoelectrochemistry of quinone radical anions has been demonstrated qualitatively by the photoassisted reduction of methyl viologen with benzoquinone and of neutral red with chloranil. Data were then collected for the estimation of quenching rate constants using Marcus-Weller theory. Reduction potentials of seven quinones were obtained in four solvents (and two aqueous mixtures) by cyclic voltammetry. The solvent effects on these potentials were studied by fitting them to the Taft relationship. The effects of proton donors were also noted. Absorption spectra of the radical anions were measured and the solvent effects noted and commented upon. From the molar absorption coefficients of the radical anions, the mean lifetimes of the excited states were estimated. Fluorescence spectra were obtained for anthraquinone and naphthaquinone radical anions and excitation energies were calculated. These values were estimated for the other quinones. Values of redox potentials for the excited radical anions were thence obtained. The Gibbs energies of the electron transfers between the excited quinone radical anions and the various substrates were obtained and hence the Gibbs energies of activation were calculated using the Marcus equation. The quenching rate constants were calculated using the Rehm-Weller equation and plotted vs. ΔG giving a characteristic Marcus plot including some data in the inverted region. The significance of the inverted region is discussed.

Coherence and discontinuity in the scaling of species' distribution patterns

The spatial distribution of a species can be characterized at many different spatial scales, from fine-scale measures of local population density to coarse-scale geographical-range structure. Previous studies have shown a degree of correlation in species' distribution patterns across narrow ranges of scales, making it possible to predict fine-scale properties from coarser-scale distributions. To test the limits of such extrapolation, we have compiled distributional information on 16 species of British plants, at scales ranging across six orders of magnitude in linear resolution (1 in to 100 km). As expected, the correlation between patterns at different spatial scales tends to degrade as the scales become more widely separated. There is, however, an abrupt breakdown in cross-scale correlations across intermediate (ca. 0.5 km) scales, suggesting that local and regional patterns are influenced by essentially non-overlapping sets of processes. The scaling discontinuity may also reflect characteristic scales of human land use in Britain, suggesting a novel method for analysing the 'footprint' of humanity on a landscape.

Action Spectra of P25 TiO2 and a visible light absorbing, carbon-modified titania in the photocatalytic degradation of stearic acid

The photonic efficiencies of films of Evonik (formerly Degussa) P25 TiO2 and carbon-modified TiO2 Kronos VLP 7000 samples are reported as a function of excitation wavelength (300–430 nm; FWHM ∼ 7.5 nm), i.e. the action spectra, for the degradation of stearic acid, a model organic for the photocatalytic destruction of solid surface organic pollutants. For each of these semiconductor photocatalysts, at 365 nm (FWHM = 18 nm), the dependence of the rate of degradation of stearic acid, upon the irradiance, I, is determined and the rate is found to be proportional to I0.65 and I0.82 for P25 and Kronos titania, respectively. Assuming this relationship holds at all wavelengths, the action spectra for two different semiconductor photocatalysts is modified by plotting, (RSA (rate of stearic acid destruction, units: molecules cm−2 s−1)/Iθ) vs. wavelength of excitation (λexcit), and both differ noticeably from those of the original (unmodified) action spectra, which are plots of (RSA/I = photonic efficiency, ξ) vs. λexcit. The shape of the modified action spectrum for P25 TiO2 is consistent with that reported by others for other organic mineralisation reactions and correlates well with diffuse reflectance data for P25 TiO2 (Kubelka–Munk plot), although there is some evidence that the active phase, in the photodegradation of stearic acid, is the anatase form present in P25. The unmodified and modified action spectra of the beige Kronos VLP 7000 TiO2 compound exhibits little or no activity in the visible i.e. (λexcit > 400 nm) and a peak at 350 nm. The Kronos powder contains a yellow/brown conjugated, extractable, organic sensitiser which has been identified by others as the species responsible for its reported photocatalytic visible light activity. But, irradiation of the Kronos powder film, with and without a stearic acid coating, in air, using UVA or visible light, bleaches rapidly (<60 min) most, if not all, of the little colour exhibited by the original Kronos powder. The photobleached form of the Kronos has a similar action spectrum to that of the unbleached form, which, in turn, appears very similar to that of P25 titania, at wavelengths >350 nm. It is proposed that the difference between the Kronos and P25 powder films at wavelengths <350 nm is due to a photodegradation-resistant, previously unidentified (but extractable using MeCN) UV-absorbing organic species in the former which screens the titania particles at these lower wavelengths. The implications of these observations are discussed briefly.

An alternative methodology in Schottky diode physics

The fabrication and electrical characterization of Schottky junction diodes have been extensively researched for three-quarters of a century since the original work of Schottky in 1938. This study breaks from the highly standardized regime of such research and provides an alternative methodology that prompts novel, more efficient applications of the adroit Schottky junction in areas such as chemical and thermal sensing. The core departure from standard Schottky diode configuration is that the metal electrode is of comparable or higher resistance than the underlying semiconductor. Further, complete electrical characterization is accomplished through recording four-probe resistance-temperature (R-D-T) characteristics of the device, where electrical sourcing and sensing is done only via the metal electrode and not directly through the semiconductor. Importantly, this results in probing a nominally unbiased junction while eliminating the need for an Ohmic contact to the semiconductor. The characteristic R-D-T plot shows two distinct regions of high (metal) and low (semiconductor) resistances at low and high temperatures, respectively, connected by a crossover region of width, DT, within which there is a large negative temperature coefficient of resistance. The R-D-T characteristic is highly sensitive to the Schottky barrier height; consequently, at a fixed temperature, R-D responds appreciably to small changes in barrier height such as that induced by absorption of a chemical species (e.g., H-2) at the interface. A theoretical model is developed to simulate the R-D-T data and applied to Pd/p-Si and Pt/p-Si Schottky diodes with a range of metal electrode resistance. The analysis gives near-perfect fits to the experimental R-D-T characteristics, yielding the junction properties as fit parameters. The modelling not only helps elucidate the underlying physics but also helps to comprehend the parameter space essential for the discussed applications. Although the primary regime of application is limited to a relatively narrow range (DT) for a given type of diode, the alternative methodology is of universal applicability to all metal-semiconductor combinations forming Schottky contacts. (C) 2015 AIP Publishing LLC.

A Correlation between the Dynamic Viscosity and Crystallisation of Felodipine from its Amorphous Polymer Solid Dispersion

Purpose Previously, it has been reported that molecular mobility determines the rate of molecular approach to crystal surfaces, while entropy relates to the probability of that approaching molecule having the desirable configuration for further growth of the existing crystal; and the free energy dictates the probability of that molecule not returning to the liquid phase1. If we plot the crystal growth rate and viscosity of a supercooled liquid in a log-log format, the relationship between the two is linear, indicating the influence viscosity has upon crystal growth rate. However, such approximation has been derived from pure drug compounds and it is apparent that further understanding of crystallization from drug-polymer solid dispersion is required in order to stabilise drugs embedded within amorphous polymeric solid dispersions. Methods Mixtures of felodipine and polymer (HPMCAS-HF, PVPK15 and Soluplus®) at specified compositions were prepared using a Restch MM200 ball mill. To examine crystal growth within amorphous solid dispersions, samples were prepared by melting 5-10 mg of ball milled mixture at 150°C for 3-5 minutes on a glass slip pre-cleaned with methanol and acetone. All prepared samples were confirmed to be crystal free by visual observation using a polarised light microscope (Olympus BX50). Prepared samples were stored at 0% RH (P2O5), inside desiccators, maintained in ovens at 80°C. For the dynamic viscosity measurement, approximately 100-200mg ball milled mixture was heated on the base plate of a rotational rheometer at 150°C for 5 minutes and the top plate was lowered to a defined gap to form a good contact with the material. The sandwiched amorphous material was heated to 80°C and the viscosity was measured. Results The equation was used to probe the correlation of viscosity to crystal growth rate. In comparison to the value of xi in log-log equation reported from pure drug compound, a value of 1.63 was obtained for FD-polymer solid dispersions irrespective of the polymer involved. &#8733 Conclusion The high xi value suggests stronger viscosity dependence may exist for amorphous FD once incorporated with amorphous polymer.

Spatial variation in adult sex ratio across multiple scales in the invasive golden apple snail, Pomacea canaliculata

Adult sex ratio (ASR) has critical effects on behavior and life history and has implications for population demography, including the invasiveness of introduced species. ASR exhibits immense variation in nature, yet the scale dependence of this variation is rarely analyzed. In this study, using the generalized multilevel models, we investigated the variation in ASR across multiple nested spatial scales and analyzed the underlying causes for an invasive species, the golden apple snail Pomacea canaliculata. We partitioned the variance in ASR to describe the variations at different scales and then included the explanatory variables at the individual and group levels to analyze the potential causes driving the variation in ASR. We firstly determined there is a significant female-biased ASR for this species when accounting for the spatial and temporal autocorrelations of sampling. We found that, counter to nearly equal distributed variation at plot, habitat and region levels, ASR showed little variation at the town level. Temperature and precipitation at the region level were significantly positively associated with ASR, whereas the individual weight, the density characteristic, and sampling time were not significant factors influencing ASR. Our study suggests that offspring sex ratio of this species may shape the general pattern of ASR in the population level while the environmental variables at the region level translate the unbiased offspring sex ratio to the female-biased ASR. Future research should consider the implications of climate warming on the female-biased ASR of this invasive species and thus on invasion pattern.