Induction of apoptosis by a cachectic-factor in murine myotubes and inhibition by eicosapentaenoic acid

Treatment of C2C12 myotubes with a tumour-derived proteolysis-inducing factor (PIF) at concentrations between 1 and 10 nM was shown to stimulate the activity of the apoptotic initiator caspases-8 and -9 and the apoptotic effector caspases-2,-3 and -6. This increased caspase activity was attenuated in myotubes pretreated with 50 μM eicosapentaenoic acid (EPA). At least part of the increase in caspase activity may be related to the increased proteasome proteolytic activity, since a caspase-3 inhibitor completely attenuated the PIF-induced increase in 'chymotrypsin-like' enzyme activity, the predominant proteolytic activity of the proteasome. However, Western blot analysis showed that PIF induced an increase in expression of the active form of caspase-3, which was also attenuated by EPA. Further Western blot analysis showed PIF increased the cytosolic content of cytochrome c, as well as expression of the pro-apoptotic protein bax but not the antiapoptotic protein bcl-2, which were both attenuated by 50 μM EPA. Induction of apoptosis by PIF in murine myotubes was confirmed by an increase in free nucleasomes formation and increased DNA fragmentation evidenced by a nucleasomal ladder typical of apoptotic cells. This process was again inhibited by pre-incubation with EPA. These results suggest that in addition to activating the proteasome, PIF induces apoptosis in C2C12 myotubes, possibly through the common intermediate arachidonic acid. Both of these processes would contribute to the loss of skeletal muscle in cancer cachexia.

Geometric Stable Laws Through Series Representations

Let (Xi ) be a sequence of i.i.d. random variables, and let N be a geometric random variable independent of (Xi ). Geometric stable distributions are weak limits of (normalized) geometric compounds, SN = X1 + · · · + XN , when the mean of N converges to infinity. By an appropriate representation of the individual summands in SN we obtain series representation of the limiting geometric stable distribution. In addition, we study the asymptotic behavior of the partial sum process SN (t) = ⅀( i=1 ... [N t] ) Xi , and derive series representations of the limiting geometric stable process and the corresponding stochastic integral. We also obtain strong invariance principles for stable and geometric stable laws.

Reliability for Beta Models

In the area of stress-strength models there has been a large amount of work as regards estimation of the reliability R = Pr(X2 < X1 ) when X1 and X2 are independent random variables belonging to the same univariate family of distributions. The algebraic form for R = Pr(X2 < X1 ) has been worked out for the majority of the well-known distributions including Normal, uniform, exponential, gamma, weibull and pareto. However, there are still many other distributions for which the form of R is not known. We have identified at least some 30 distributions with no known form for R. In this paper we consider some of these distributions and derive the corresponding forms for the reliability R. The calculations involve the use of various special functions.

Commuting Nonselfadjoint Operators and their Characteristic Operator-Functions

* Partially supported by Grant MM-428/94 of MESC.

Biomaterial interactions with compromised tissue surfaces

This thesis is concerned with the nature of biomaterial interactions with compromised host tissue sites. Both ocular and dermal tissues can be wounded, following injury, disease or surgery, and consequently require the use of a biomaterial. Clear analogies exist between the cornea/tear film/contact lens and the dermal wound bed/wound fluid/skin adhesive wound dressing. The work described in this thesis builds upon established biochemistry to examine specific aspects of the interaction of biomaterials with compromised ocular and dermal tissue sites, with a particular focus on the role of vitronectin. Vitronectin is a prominent cell adhesion glycoprotein present in both tear fluid and wound fluid, and has a role in the regulation and upregulation of plasmin. The interaction of contact lenses with the cornea was assessed by a novel on-lens cell-based vitronectin assay technique. Vitronectin mapping showed that vitronectin-mediated cell adhesion to contact lens surfaces was due to the contact lens-corneal mechanical interaction rather than deposition out of the tear film. This deposition is associated predominantly with the peripheral region of the posterior contact lens surface. The locus of vitronectin deposition on the contact lens surface, which is affected by material modulus, is potentially an important factor in the generation of plasmin in the posterior tear film. Use of the vitronectin mapping technique on ex vivo bandage contact lenses revealed greater vitronectin-mediated cell adhesion to the contact lens surfaces in comparison to lenses worn in the healthy eye. The results suggest that vitronectin is more readily deposited from the impaired corneal tissue bed than the intact healthy tissue bed. Significantly, subjects with a deficient tear film were found to deposit high vitronectin-mediated cell adhesion levels to the BCL surface, thus highlighting the influence of the contact lens-tissue interaction upon deposition. Biomimetic principles imply that adhesive materials for wound applications, including hydrogels and hydrocolloids, should closely match the surface energy parameters of skin. The surface properties of hydrocolloid adhesives were found to be easily modified by contact with siliconised plastic release liners. In contrast, paper release liners did not significantly affect the adhesive surface properties. In order to characterise such materials in the actual wound environment, which is an extremely challenging task, preliminary considerations for the design of an artificial wound fluid model from an animal serum base were addressed.

Invariants of Unipotent Transformations Acting on Noetherian Relatively Free Algebras

2000 Mathematics Subject Classification: 16R10, 16R30.

The Wiener, Eccentric Connectivity and Zagreb Indices of the Hierarchical Product of Graphs

Let G1 = (V1, E1) and G2 = (V2, E2) be two graphs having a distinguished or root vertex, labeled 0. The hierarchical product G2 ⊓ G1 of G2 and G1 is a graph with vertex set V2 × V1. Two vertices y2y1 and x2x1 are adjacent if and only if y1x1 ∈ E1 and y2 = x2; or y2x2 ∈ E2 and y1 = x1 = 0. In this paper, the Wiener, eccentric connectivity and Zagreb indices of this new operation of graphs are computed. As an application, these topological indices for a class of alkanes are computed. ACM Computing Classification System (1998): G.2.2, G.2.3.

On Optimal Quadratic Lagrange Interpolation: Extremal Node Systems with Minimal Lebesgue Constant via Symbolic Computation

ACM Computing Classification System (1998): G.1.1, G.1.2.

Solvability of an Infinite System of Singular Integral Equations

2000 Mathematics Subject Classification: 45G15, 26A33, 32A55, 46E15.

Exact Solutions of Nonlocal BVPs for the Multidimensional Heat Equations

MSC 2010: 44A35, 44A45, 44A40, 35K20, 35K05

Polynomial automorphisms over finite fields: Mimicking tame maps by the Derksen group

2010 Mathematics Subject Classification: 14L99, 14R10, 20B27.

Growth of some varieties of Leibniz-Poisson algebras

2010 Mathematics Subject Classification: 17A32, 17B63.

A fenntarthatósági szempontok érvényesülése a paksi atomerőmű bővítése kapcsán

Három szakmai műhely, a Budapesti Corvinus Egyetem Stratégiai és Nemzetközi Menedzsment Kutatóközpontja, az Óbudai Egyetem Villamosenergetikai Intézete Megújuló Energiaforrás Kutatóhelye valamint az Eötvös Loránd Tudományegyetem Környezet- és Tájföldrajzi Tanszéke energiagazdálkodással foglalkozó kutatói egyetemközi munkacsoportot hoztak létre annak feltérképezésére, hogy milyen módon fedezhető fenntartható módszerekkel hazánk energiaellátása. Meggyőződésünk, hogy a stratégiai tervezési feladat komplexitása megköveteli az interdiszciplináris közelítésmódot, amely az energetika és a környezetgazdálkodás értő művelői mellett a társadalomtudományok területén dolgozó szakértők bevonását is szükségessé teszi a közeli jövőben. A közelmúlt eseményei a munkacsoport vizsgálódásának fókuszát az új paksi atomerőmű építésének hosszú távú következményeire irányították, hiszen a paksi erőmű bővítése nem kizárólagos opció, csak egy változat a lehetséges energiaellátási megoldások közül. Az eddig felszínre került elsődleges kutatási eredményeink az alábbiakban foglalhatók össze: Számos műszakilag elképzelhető alternatíva létezik Magyarország villamos energia ellátásának tekintetében. Műszakilag megvalósítható akár a tisztán hazai szén alapú, tisztán gáz alapú villamosenergia-termelés, de üzemképes a jelenlegi portfólió is. Hasonlóképpen a nukleáris vagy éppen a megújuló részarány növelése is elképzelhető. Ugyanakkor látni kell, hogy az energiatervezést nem egyszerűsíthetjük le pusztán technikai, műszaki vonatkozások vizsgálatára.

Thermal imaging as a biometrics approach to facial signature authentication

This dissertation develops an image processing framework with unique feature extraction and similarity measurements for human face recognition in the thermal mid-wave infrared portion of the electromagnetic spectrum. The goals of this research is to design specialized algorithms that would extract facial vasculature information, create a thermal facial signature and identify the individual. The objective is to use such findings in support of a biometrics system for human identification with a high degree of accuracy and a high degree of reliability. This last assertion is due to the minimal to no risk for potential alteration of the intrinsic physiological characteristics seen through thermal infrared imaging. The proposed thermal facial signature recognition is fully integrated and consolidates the main and critical steps of feature extraction, registration, matching through similarity measures, and validation through testing our algorithm on a database, referred to as C-X1, provided by the Computer Vision Research Laboratory at the University of Notre Dame. Feature extraction was accomplished by first registering the infrared images to a reference image using the functional MRI of the Brain’s (FMRIB’s) Linear Image Registration Tool (FLIRT) modified to suit thermal infrared images. This was followed by segmentation of the facial region using an advanced localized contouring algorithm applied on anisotropically diffused thermal images. Thermal feature extraction from facial images was attained by performing morphological operations such as opening and top-hat segmentation to yield thermal signatures for each subject. Four thermal images taken over a period of six months were used to generate thermal signatures and a thermal template for each subject, the thermal template contains only the most prevalent and consistent features. Finally a similarity measure technique was used to match signatures to templates and the Principal Component Analysis (PCA) was used to validate the results of the matching process. Thirteen subjects were used for testing the developed technique on an in-house thermal imaging system. The matching using an Euclidean-based similarity measure showed 88% accuracy in the case of skeletonized signatures and templates, we obtained 90% accuracy for anisotropically diffused signatures and templates. We also employed the Manhattan-based similarity measure and obtained an accuracy of 90.39% for skeletonized and diffused templates and signatures. It was found that an average 18.9% improvement in the similarity measure was obtained when using diffused templates. The Euclidean- and Manhattan-based similarity measure was also applied to skeletonized signatures and templates of 25 subjects in the C-X1 database. The highly accurate results obtained in the matching process along with the generalized design process clearly demonstrate the ability of the thermal infrared system to be used on other thermal imaging based systems and related databases. A novel user-initialization registration of thermal facial images has been successfully implemented. Furthermore, the novel approach at developing a thermal signature template using four images taken at various times ensured that unforeseen changes in the vasculature did not affect the biometric matching process as it relied on consistent thermal features.

Alterations in Glutathione Levels and Apoptotic Regulators Are Associated with Acquisition of Arsenic Trioxide Resistance in Multiple Myeloma

Arsenic trioxide (ATO) has been tested in relapsed/refractory multiple myeloma with limited success. In order to better understand drug mechanism and resistance pathways in myeloma we generated an ATO-resistant cell line, 8226/S-ATOR05, with an IC50 that is 2–3-fold higher than control cell lines and significantly higher than clinically achievable concentrations. Interestingly we found two parallel pathways governing resistance to ATO in 8226/S-ATOR05, and the relevance of these pathways appears to be linked to the concentration of ATO used. We found changes in the expression of Bcl-2 family proteins Bfl-1 and Noxa as well as an increase in cellular glutathione (GSH) levels. At low, clinically achievable concentrations, resistance was primarily associated with an increase in expression of the anti-apoptotic protein Bfl-1 and a decrease in expression of the pro-apoptotic protein Noxa. However, as the concentration of ATO increased, elevated levels of intracellular GSH in 8226/S-ATOR05 became the primary mechanism of ATO resistance. Removal of arsenic selection resulted in a loss of the resistance phenotype, with cells becoming sensitive to high concentrations of ATO within 7 days following drug removal, indicating changes associated with high level resistance (elevated GSH) are dependent upon the presence of arsenic. Conversely, not until 50 days without arsenic did cells once again become sensitive to clinically relevant doses of ATO, coinciding with a decrease in the expression of Bfl-1. In addition we found cross-resistance to melphalan and doxorubicin in 8226/S-ATOR05, suggesting ATO-resistance pathways may also be involved in resistance to other chemotherapeutic agents used in the treatment of multiple myeloma.