Panel performance: Modelling variation in sensory profiling data by multiway analysis

Sensory profiling data is essentially three-way data where samples, attributes and assessors are the three dimensions of information. It is common practice to average over the assessors and focus the analysis on the relations between samples and sensory descriptors. However, since assessor reliability can not be controlled in advance, posthoc analysis on assessors is needed to assess performance of the individual and at the panel level. For this purpose, multiway analysis is a very efficient data method as it provides information on samples, attributes and assessors, simultaneously [1]. PARAllel FACtor (PARAFAC) analysis is one of the most used multiway methods in sensory analysis [2][3]. It is based on two basic assumptions: 1) there exist latent variables behind the identified sensory descriptors describing the variation among the products; 2) assessors have different sensitivities to these common latent variables. However, assessors may perceive the factors differently, so the assumption of “common latent variables” becomes questionable. This may happen when the panel is not well trained and/or the samples present subtle differences difficult to detect. In this work a more flexible approach to the analysis of sensory data is presented. Specifically, the work proposes to use PARAFAC2 modelling [4] as it allows each assessor to have an individual idiosyncratic perceptive model. The data was obtained from a descriptive sensory analysis of organic milk samples. Results show that PARAFAC2 is very useful to highlight disagreement in the panel on specific attributes and to detect outlying assessors. In addition, by using PARAFAC2 an improvement in the description of samples is also achieved. On the other hand, PARAFAC has to be preferred to PARAFAC2 when a good panel agreement is observed, since it provides more stable solutions and no further gain in information is obtained from PARAFAC2. Finally, the work proposes an index to measure the performance of each assessor based on individual sensitivity and reproducibility

Unusual products of the aqueous chlorination of atenolol

The reaction of the drug atenolol with hypochlorite under conditions that simulate wastewater disinfection was investigated. The pharmaceutical reacted in 1 h yielding three products that were separated by chromatographic techniques and characterized by spectroscopic features. Two unusual products 2-(4-(3-(chloro(2-chloropropan- 2-yl)amino)-2-hydroxypropoxy) phenyl) acetamide and 2-(4- (3-formamido- 2-hydroxypropoxy) phenyl) acetamide were obtained along with 2-(4-hydroxyphenyl) acetamide. When the reaction was stopped at shorter times only 2-(4-(3-amino-2-hydroxypropoxy) phenyl) acetamide and the dichlorinated product were detected. Tests performed on the seeds of Lactuca sativa show that chlorinated products have phytotoxic activity

Monitoring panel performance within and between sensory experiments by multi-way analysis

In sensory analysis a panel of trained assessors evaluates a set of samples according to specific sensory descriptors. The training improves objectivity and reliability of assessments. However, there can be individual differences between assessors left after the training that should be taken into account in the analysis. Monitoring panel performance is then crucial for optimal sensory evaluations. The quality of the results is strongly dependent on the performance of each assessor and of the panel as a whole. The present work proposes to analyze the panel performance within single sensory evaluations and between consecutive evaluations. The basic idea is to use multi-way models to handle the three-way nature of the sensory data. Specifically, a PARAFAC model is used to investigate the panel performance in the single experiment. N-PLS model is used to test the predictive ability of the panel on each experiment. A PARAFAC model is also used for monitoring panel performance over different experiments

Co-targeting of Bcl-2 and mTOR pathway triggers synergistic apoptosis in BH3 mimetics resistant acute lymphoblastic leukemia

Several chemo-resistance mechanisms including the Bcl-2 protein family overexpression and constitutive activation of the PI3K/Akt/mTOR signaling have been documented in acute lymphoblastic leukemia (ALL), encouraging targeted approaches to circumvent this clinical problem. Here we analyzed the activity of the BH3 mimetic ABT-737 in ALL, exploring the synergistic effects with the mTOR inhibitor CCI-779 on ABT-737 resistant cells. We showed that a low Mcl-1/Bcl-2 plus Bcl-xL protein ratio determined ABT-737 responsiveness. ABT-737 exposure further decreased Mcl-1, inducing apoptosis on sensitive models and primary samples, while not affecting resistant cells. Co-inhibition of Bcl-2 and the mTOR pathway resulted cytotoxic on ABT-737 resistant models, by downregulating mTORC1 activity and Mcl-1 in a proteasome-independent manner. Although Mcl-1 seemed to be critical, ectopic modulation did not correlate with apoptosis changes. Importantly, dual targeting proved effective on ABT-737 resistant samples, showing additive/synergistic effects. Together, our results show the efficacy of BH3 mimetics as single agent in the majority of the ALL samples and demonstrate that resistance to ABT-737 mostly correlated with Mcl-1 overexpression. Co-targeting of the Bcl-2 protein family and mTOR pathway enhanced drug-induced cytotoxicity by suppressing Mcl-1, providing a novel therapeutic approach to overcome BH3 mimetics resistance in ALL

Leukocyte, Rather than Tumor-produced SPARC, Determines Stroma and Collagen Type IV Deposition in Mammary Carcinoma

Secreted protein, acidic and rich in cysteine (SPARC), also known as osteonectin or BM-40, is a Ca2+-binding matricellular glycoprotein involved in development, wound healing, and neoplasia. However, the role of SPARC in tumors is ill defined mostly because it is expressed by both tumor and stromal cells, especially inflammatory cells. We analyzed the respective roles of host- and tumor-derived SPARC in wild-type and congenic SPARC knockout (SPARC−/−) mice on a BALB/c genetic background injected into the mammary fat pad with SPARC-producing mammary carcinoma cells derived from c-erB2 transgenic BALB/c mice. Reduced tumor growth but massive parenchyma infiltration, with large areas of necrosis and impaired vascularization were observed in SPARC−/− mice. Immunohistochemical analysis showed a defect in collagen type IV deposition in the stroma of lobular tumors from SPARC−/− mice. Chimeric mice expressing SPARC only in bone marrow–derived cells were able to organize peritumoral and perilobular stroma, whereas reciprocal chimeras transplanted with bone marrow from SPARC−/− mice developed tumors with less defined lobular structures, lacking assembled collagen type IV and with a parenchyma heavily infiltrated by leukocytes. Together, the data indicate that SPARC produced by host leukocytes, rather than the tumor, determines the assembly and function of tumor-associated stroma through the organization of collagen type IV

Interaction of plant amine oxidases with diaminoethers

Polyamines are ubiquitous compounds, which are involved in crucial physiological events including cell growth and differentiation. The catabolic oxidative degradation of polyamines is catalyzed by quinoprotein copper-containing amine oxidases (CAOs) and flavoprotein polyamine oxidases (PAOs). Various synthetic polyamine analogs and polyamine derivatives have been reported, which represent important tools (substrates or inhibitors) in the study of catalytic properties of the enzymes. In this work, two related compounds were studied in the reactions with plant amine oxidases: 1,8-diamino-3,6-dioxaoctane (DADO) and 1,10-bis(2- pyridinylmethyl)-4,7-dioxa-1,10-diazadecane (BPDD). Based on activity and stoichiometry assays together with spectrophotometric measurements, DADO can be considered a good substrate for grass pea, lentil and E. characias CAOs with Km values in the range 10-4 – 10-3 M. Its oxidative degradation produces the corresponding aminoaldehyde 8-amino-3,6-dioxaoctanal, which does not undergo spontaneous cyclization (as it is known for the oxidation products of natural substrates putrescine, cadaverine and spermidine) or polymerization in the reaction mixture. Conversely, oat PAO does not oxidize DADO and is only weakly inhibited by the compound (Ki = 1.6 mM towards putrescine). BPDD was found to be a competitive inhibitor of both CAOs and PAOs with Ki values of 10-4 M. DADO could be suggested as a potential affinity ligand for CAOs

Self-chemisorption of azurin on functionalized oxide surfaces for the implementation of biomolecular devices

Abstract In this work, we investigate the formation of redox protein Azurin (Az) monolayers on functionalized oxygen exposing surfaces. These metallo-proteins mediate electron transfer in the denitrifying chain of Pseudomonas bacteria and exhibit self-assembly properties, therefore they are good candidates for bio-electronic applications. Azurin monolayers are self-assembled onto silane functionalized surfaces and characterized by atomic force microscopy (AFM). We show also that a biomolecular field effect transistor (FET) in the solid state can be implemented by interconnecting an Azurin monolayer immobilized on SiO 2 with two gold nanoelectrodes. Transport experiments, carried out at room temperature and ambient pressure, show FET behavior with conduction modulated by the gate potential

HYDRAULIC RISK ASSESSMENT IN ARCHAEOLOGICAL SITES SUPPORTED BY AN INTEGRATED DIGITAL SURVEY – CFD (COMPUTATIONAL FLUID DYNAMICS) MONITORING APPROACH

Abstract. This paper presents a methodological approach for analysing and evaluating hydraulic risks in complex archaeological areas, and thereby substantially improve general preservation and conservation efforts involving cultural heritage.The hypogeum of Calaforno (province of Ragusa, Sicily) represents a unique sample of rock-cut architecture in terms of size and architectural features, and an ideal candidate for the case study due to its high historical, archaeological and cultural significance, as well as its intrinsic fragility and criticality associated with hydrogeological and seismic factors.The interdisciplinary research approach involved archaeological and engineering contributions towards the development of numerical models for the assessment of hydraulic risks threatening archaeological heritage. The morphological characteristics of the site rendered the use of a Laser Scanner necessary for three-dimensional survey.The prehistoric structures currently undergoing excavation outside the main entrance of the monument have raised concerns regarding the impact of the Manna stream, which flows a few meters from the main entrance to the hypogeum, which has seen periodic flooding in some of its rooms. Simulations of these flooding events were performed in order to attain better understanding of the hydraulic phenomena influencing the site, especially regarding the dynamics associated with surface runoff.The interdisciplinary approach to this research, combining in-depth archaeological expertise with digital 3D surveying and modelling technologies, has proven fundamental to the effective monitoring of this morphologically complex site, and should perhaps be considered integral to any preventive assessment and risk management initiative involving cultural heritage

ESOPE-Equivalent Pulsing Protocols for Calcium Electroporation: An In Vitro Optimization Study on 2 Cancer Cell Models

Reversible electroporation is used to increase the uptake of chemotherapeutic drugs in local tumor treatment (electrochemotherapy) by applying the pulsing protocol (8 rectangular pulses, 1000 V/cm, 100 µs) standardized in the framework of the European Standard Operating Procedure on Electrochemotherapy multicenter trial. Currently, new electrochemotherapy strategies are under development to extend its applicability to tumors with different histology. Electrical parameters and drug type are critical factors. A possible approach is to test pulse parameters different from European Standard Operating Procedure on Electrochemotherapy but with comparable electroporation yield (European Standard Operating Procedure on Electrochemotherapy-equivalent protocols). Moreover, the use of non-toxic drugs combined with electroporation represents the new frontier for electrochemotherapy applications; calcium electroporation has been recently proposed as a simple tool for anticancer therapy. In vitro investigations facilitate the optimization of electrical parameters and drugs for in vivo and clinical testing. In this optimization study, new pulsing protocols have been tested by increasing the pulse number and reducing the electric field with respect to the standard. European Standard Operating Procedure on Electrochemotherapy-equivalent protocols have been identified in HL-60 and A431 cancer cell models, and a higher sensitivity in terms of electroporation yield has been recorded in HL-60 cells. Moreover, cell killing efficacy of European Standard Operating Procedure on Electrochemotherapy-equivalent protocols has been demonstrated in the presence of increasing calcium concentrations on both cell lines. Equivalent European Standard Operating Procedure on Electrochemotherapy protocols can be used to optimize the therapeutic effects in the clinic, where different regions of the same cancer tissue, with different electrical properties, might result in a differential electroporation yield of the standard protocol over the same tissue, or, eventually, in an override of the operational limits of the instrument. Moreover, using calcium can help overcome the drawbacks of standard drugs (side effects, high costs, difficult handling, preparation, and storage procedures). These results support the possibility of new treatment options in both standard electrochemotherapy and calcium electroporation, with clear advantages in the clinic