Kinetic modelling of textural changes in ready-to-eat breakfast cereals during soaking in semi-skimmed milk

Summary Ready‐to‐eat breakfast cereals immersed in milk undergo undesirable changes in texture because of sudden moisture uptake. The textural changes are ascribable to a plasticizing effect of water, which modifies the mechanical strength of products by softening the starch/protein matrix. In this work, some textural parameters of different cereal flakes were derived from the force–displacement curves monitored during 300 s of immersion in milk. Hardness loss, deformability increment and changes in the force–displacement curve profile were calculated and plotted against soaking time. The application of a sugar coating process to a model cereal flake increased the initial product hardness and improved the preservation of the textural parameters during immersion. The Peleg model closely fitted the experimental data, with regression coefficients from 0.967 to 0.999.     

Good teaching inputs do not correspond to desired responses in ecological neural networks

In this paper we analyze how supervised learning occurs in ecological neural networks, i.e. networks that interact with an autonomous external environment and, therefore, at least partially determine with their behavior their own input. Using an evolutionary method for selecting good teaching inputs we surprisingly find that to obtain a desired outputX it is better to use a teaching input different fromX. To explain this fact we claim that teaching inputs in ecological networks have two different effects: (a) to reduce the discrepancy between the actual output of the network and the teaching input, (b) to modify the network's behavior and, as a consequence, the network's learning experiences. Evolved teaching inputs appear to represent a compromise between these two needs. We finally show that evolved teaching inputs that are allowed to change during the learning process function differently at different stages of learning, first giving more weight to (b) and, later on, to (a).     

Synthesis and antitumor evaluation of 2,5-disubstituted-indazolo[4, 3-gh]isoquinolin-6(2H)-ones (9-aza-anthrapyrazoles)

The synthesis and antitumor evaluation of 2, 5-disubstituted-indazolo[4,3-gh]isoquinolin-6(2H)-ones (9-aza-APs) are described. The key intermediates in the synthesis are benz[g]isoquinoline-5,10-diones which are substituted at positions 6 and 9 with groups of different nucleofugacity for SNAr displacements. The initial displacement of fluoride by a substituted hydrazine leads to the pyrazole analogues. Substitution of the remaining leaving group by an amine or BOC-protected amines leads to the 9-aza-APs 12. These analogues were converted into their maleate or hydrochloride salts 13. In two cases, namely, 13x and 13z, sidearm buildup was also employed in the synthetic pathway. In vitro evaluation of 9-aza-APs against the human colon tumor cell line LoVo uncovered for most of the compounds a cytotoxic potency lower than that of DuP-941 or mitoxantrone and comparable to that of doxorubicin. Only analogues 13c, 13n, and 13ff were as cytotoxic as DuP-941. Interestingly, while DuP-941 was highly cross-resistant in the LoVo cell line resistant to doxorubicin (LoVo/Dx), the 9-aza-APs carrying a distal lipophilic tertiary amine moiety in both chains were capable of overcoming the MDR resistance induced in this cell line. The 9-aza-APs show outstanding in vivo antitumor activity against both systemic P388 murine leukemia and MX-1 human mammary carcinoma transplanted in nude mice. At their optimal dosages, congeners 13a-c, 13f, 13n, 13q, 13x, and 13dd were highly effective against P388 leukemia with T/C% of 200-381, while the T/C% value of DuP-941 was 147. In the MX-1 tumor model, 24 compounds elicited percentages of tumor weight inhibitions (TWI) ranging from 50% to 99%. Congeners 13d, 13k, 13l, 13x, 13z, and 13ee emerged as the most effective ones, with TWI% 96, simliar to that of DuP-941 (TWI% = 95). On the basis of their efficacy profile in additional experimental tumors and lack of cardiotoxicity in preclinical models, two congeners have surfaced as potential clinical candidates.     

The Tenet experience and the design of protocols for integrated-services internetworks

The research done by the Tenet Group in multimedia networking has reached a point where it may be useful to reflect on the significance of its results for the current debate on how integrated-services internetworks should be designed. Such reflections constitute the main subject of this paper. The principles of the work and the conclusions reached so far by the Tenet researchers are discussed in the light of the conflict between the two major technologies being proposed to build future information infrastructures: namely, the Internet and the ATM technologies. The Tenet approach suggests one feasible way for resolving the conflict to the advantage of all the users of those infrastructures. This paper discusses various fundamental aspects of integrated-services network design: the choice of the service model, the type of charging policy to be adopted, and the selection of a suitable architecture.     

Steel-to-concrete bond after concrete splitting: test results

The definite trend towards the use of large-diameter rebars and the introduction of high-strength steels (f _y=500 to 600 MPa) make it necessary to study the effects of longitudinal splitting on the steel-to-concrete bond. The study of splitting effects requires firstly basic tests to be performed in order to gather experimental information on bond and confinement stresses acting at the bar-to-concrete interface. For this purpose, three series of tests were recently carried out at the Politecnico di Milano. The results make it possible to ascertain a few basic properties of the bond after concrete splitting, and to formulate empirical constitutive laws regarding the stresses and the displacements (bar slip and opening of the splitting crack). All specimens consisted of a short deformed bar embedded in a concrete block, which had a preformed splitting crack in the plane passing through the bar axis: twelve specimens (Tests A and C) were fitted up with a round deformed bar having crescent-shaped lugs (D_b=18 mm); seven specimens (Tests B) were fitted up with a specially machined deformed bar having a rectangular cross-section and straigth, lugs, so that concrete deterioration close to the bar could be investigated at the surface of the specimen, by means of the moiré technique. The tests were carried out at constant slip rate, up to very large slip values ( ); both the ascending and the descending branches of the stress-slip curves were measured, for four different values of the opening of the splitting crack. The agreement among the results of the three series is generally satisfactory and often very good: consequently, constitutive laws regarding the four main variables (crack opening and bar slip, shear and confinement stresses) can be worked out, as will be shown in a companion paper on constitutive relationships and on concrete deterioration at the bar-to-concrete interface.     

Thermal evolution and mechanical properties of vitreous fibres in the SiO2-Li2O-TiO2-Al2O3 system

The thermal evolution of glass fibres of the SiO₂-Li₂O-TiO₂-Al₂O₃ system has been investigated by X-ray diffraction, DTA and SEM. Within the range of the compositions investigated (2 to 10 mol % TiO₂) SEM and SAXS measurements on bulk materials have shown that a small addition of Al₂O₃ (3 mol %) does not modify the limits of the immiscibility region present in the ternary system SiO₂-LiO₂-TiO₂. Within this region TiO₂-rich droplets are more than likely to be formed. As to tensile strength, the asquenched fibres of the composition placed within the immiscibility dome give higher values than that obtained outside the liquid-liquid region and these values are higher than those measured on E-glass fibres. A slight crystallization in all the fibres leads to a continuous decrease of the initial tensile strength. With regards to the crystal phases presented by the crystallized fibres, the first exothermic peak is due to the simultaneous crystallization of-quartz (ss) and lithium disilicate whereas the second peak is due, most probably, to a-quartz (ss) -spodumene (ss) phase transformation as well as to the formation of Li₂TiSiO₅. The path of crystallization of the other detected Ti-compounds is similar to that proposed by Furukawa and White.     

High-Fat Diet Leads to Reduced Protein O-GlcNAcylation and Mitochondrial Defects Promoting the Development of Alzheimer’s Disease Signatures

The disturbance of protein O-GlcNAcylation is emerging as a possible link between altered brain metabolism and the progression of neurodegeneration. As observed in brains with Alzheimer’s disease (AD), flaws of the cerebral glucose uptake translate into reduced protein O-GlcNAcylation, which promote the formation of pathological hallmarks. A high-fat diet (HFD) is known to foster metabolic dysregulation and insulin resistance in the brain and such effects have been associated with the reduction of cognitive performances. Remarkably, a significant role in HFD-related cognitive decline might be played by aberrant protein O-GlcNAcylation by triggering the development of AD signature and mitochondrial impairment. Our data support the impairment of total protein O-GlcNAcylation profile both in the brain of mice subjected to a 6-week high-fat-diet (HFD) and in our in vitro transposition on SH-SY5Y cells. The reduction of protein O-GlcNAcylation was associated with the development of insulin resistance, induced by overfeeding (i.e., defective insulin signaling and reduced mitochondrial activity), which promoted the dysregulation of the hexosamine biosynthetic pathway (HBP) flux, through the AMPK-driven reduction of GFAT1 activation. Further, we observed that a HFD induced the selective impairment of O-GlcNAcylated-tau and of O-GlcNAcylated-Complex I subunit NDUFB8, thus resulting in tau toxicity and reduced respiratory chain functionality respectively, highlighting the involvement of this posttranslational modification in the neurodegenerative process.     

Confocal Blood Flow Videomicroscopy of Thrombus Formation over Human Arteries and Local Targeting of P2X7

Atherothrombosis exposes vascular components to blood. Currently, new antithrombotic therapies are emerging. Herein we investigated thrombogenesis of human arteries with/without atherosclerosis, and the interaction of coagulation and vascular components, we and explored the anti-thrombogenic efficacy of blockade of the P2X purinoceptor 7 (P2X7). A confocal blood flow videomicroscopy system was performed on cryosections of internal mammary artery (IMA) or carotid plaque (CPL) determining/localizing platelets and fibrin. Blood from healthy donors elicited thrombi over arterial layers. Confocal microscopy associated thrombus with tissue presence of collagen type I, laminin, fibrin(ogen) and tissue factor (TF). The addition of antibodies blocking TF (aTF) or factor XI (aFXI) to blood significantly reduced fibrin deposition, variable platelet aggregation and aTF + aFXI almost abolished thrombus formation, showing synergy between coagulation pathways. A scarce effect of aTF over sub-endothelial regions, more abundant in tissue TF and bundles of laminin and collagen type I than deep intima, may suggest tissue thrombogenicity as molecular structure-related. Consistently with TF-related vascular function and expression of P2X7, the sections from CPL but not IMA tissue cultures pre-treated with the P2X7 antagonist A740003 demonstrated poor thrombogenesis in flow experiments. These data hint to local targeting studies on P2X7 modulation for atherothrombosis prevention/therapy.     

Proinflammatory Interleukin-33 Induces Dichotomic Effects on Cell Proliferation in Normal Gastric Epithelium and Gastric Cancer

Interleukin (IL)-33 is a member of the interleukin (IL)-1 family of cytokines linked to the development of inflammatory conditions and cancer in the gastrointestinal tract. This study is designed to investigate whether IL-33 has a direct effect on human gastric epithelial cells (GES-1), the human gastric adenocarcinoma cell line (AGS), and the gastric carcinoma cell line (NCI-N87) by assessing its role in the regulation of cell proliferation, migration, cell cycle, and apoptosis. Cell cycle regulation was also determined in ex vivo gastric cancer samples obtained during endoscopy and surgical procedures. Cell lines and tissue samples underwent stimulation with rhIL-33. Proliferation was assessed by XTT and CFSE assays, migration by wound healing assay, and apoptosis by caspase 3/7 activity assay and annexin V assay. Cell cycle was analyzed by means of propidium iodine assay, and gene expression regulation was assessed by RT-PCR profiling. We found that IL-33 has an antiproliferative and proapoptotic effect on cancer cell lines, and it can stimulate proliferation and reduce apoptosis in normal epithelial cell lines. These effects were also confirmed by the analysis of cell cycle gene expression, which showed a reduced expression of pro-proliferative genes in cancer cells, particularly in genes involved in G0/G1 and G2/M checkpoints. These results were confirmed by gene expression analysis on bioptic and surgical specimens. The aforementioned results indicate that IL-33 may be involved in cell proliferation in an environment- and cell-type-dependent manner.