Diagnóstico molecular da alteração mutagênica nt 230 (del4) no gene MDR1 em cães

P-glycoprotein is an adenosine triphosphate (ATP)-driven drug efflux carrier responsible for transport of xenobiotics and multiple classes of drugs, many usually use in veterinary medicine. Encoded by MDR1 gene, also referred to as ABCB1, located on chromosome 14, is expressed in many tissues with secretory or excretory functions, such as liver, kidney and intestine, where it limits drug absorption from the gut and promotes drug excretion into the bile and urine of their substrates. In 2001, a 4 base pair gene deletion mutation in the canine MDR1 gene was identified as MDR1-1▲, ABCB1-1▲, MDR1 MDR1 nt 230 (del4) and associated with an non-functional Pglycoprotein. The clinical correlation is the (hyper) sensitivity of certain dogs breeds, mostly collies, to a few classes of drugs such as anticancer drugs (doxorubicin, vincristine, vinblastine), immunosuppressants (cyclosporine), antiparasitic drugs (ivermectin, moxidectin), steroids hormones (aldosterone, cortisol, dexamethasone), antimicrobial agents (tetracycline, doxycycline, levofloxacin, ketoconazole, itraconazole), analgesics (morphine, methadone), antidiarrheals (loperamide), antiepileptic agents (phenothiazine), cardiac drugs (digoxin, diltiazem, verapamil, talinolol) and others. Dogs with homozygous MDR1 nt 230 (del4) MDR1 mutations (MDR1 - / -) have a higher predisposition to intoxication with substrates of P-gp than heterozygous (MDR1 + / -) and these are more likely than dogs homozygous nonmutant (MDR1 +/ +). After the identification of nt230 (del4) mutation, several molecular techniques have been developed for identification of mutant animals as a diagnostic method. The importance of molecular diagnosis is, after the identification of mutant animals, establish treatment protocols safe, exclude this animals from reproduction (genetic selection program) and investigating the history of adverse drugs reactions... (Complete abstract click electronic access below)

Geochemistry of eolian dust from sediment core LL44-GPC-3

The large-diameter piston core LL44-GPC3 from the central North Pacific Ocean records continuous sedimentation of eolian dust since the Late Cretaceous. Two intervals resolved by Nd and Pb isotopic data relate to dust coming from America (prior to ~40 Ma) and dust coming from Asia (since ~40 Ma). The Intertropical Convergence Zone (ITCZ) separates these depositional regimes today and may have been at a paleolatitude of ~23°N prior to 40 Ma. Such a northerly location of the ITCZ is consistent with sluggish atmospheric circulation and warm climate for the Northern Hemisphere of the early to middle Eocene. Since ~40 Ma, correlations between Nd (~7.55 > epsilon-Nd(t) > ~10.81) and Pb (18.625 < 206/4Pb < 18.879; 15.624 < 207/4Pb < 15.666; 38.611 < 208/4Pb < 38.960; 0.8294 < 207/6Pb < 0.8389; 2.0539 < 208/6Pb < 2.0743) isotopes reflect the progressive drying of central Asia triggered by the westward retreat of the paleo-Tethys. Comparisons between the changes with time in the isotopically well-defined dust flux and Nd and Pb isotopic compositions of Pacific deep water allow one to draw two major conclusions: (1) dust-bound Nd became a resolvable contribution to Pacific seawater only after the one order of magnitude increase in dust flux starting at ~3.5 Ma. Therefore eolian Nd was unimportant for Pacific seawater Nd prior to 3.5 Ma. (2) The lack of a response of Pacific deep water Pb to this huge flux increase suggests that dust-bound Pb has never been important. Instead, mobile Pb associated with island arc volcanic exhalatives probably consists of a significant contribution to Pacific deep water Pb and possibly to seawater elsewhere far away from landmasses.

Element analyses and isotopic composition of basalts from the western Pacific

New Sr- Nd- and Pb-isotopic and trace element data are presented on basalts from the Sulu and Celebes Basins, and the submerged Cagayan Ridge Arc (Western Pacific), recently sampled during Ocean Drilling Program Leg 124. Drilling has shown that the Sulu Basin developed about 18 Ma ago as a backarc basin, associated with the now submerged Cagayan Ridge Arc, whereas the Celebes Basin was generated about 43 Ma ago, contemporaneous with a general plate reorganisation in the Western Pacifc, subsequently developing as an open ocean receiving pelagic sediments until the middle Miocene. In both basins, a late middle Miocene collision phase and the onset of volcanic activity on adjacent arcs in the late Miocene are recorded. Covariations between 87Sr/86Sr and 143Nd/144Nd show that the seafoor basalts from both the Sulu and Celebes Basins are isotopically similar to depleted Indian mid-ocean ridge basalts (MORB), and distinct from East Pacifc Rise MORB, defining a single negative correlation. The Cagayan Arc volcanics are different, in that they have distinctly lower epsilon-Ne(T) for a given epsilon-Sr(T), compared to Sulu and Celebes basalts. In the 207Pb/204Pb and 208Pb/204Pb versus 206Pb/204Pb diagrams, the Celebes, Sulu and Cagayan rocks all plot distinctly above the Northern Hemisphere Reference Line, with high Delta 7/4 Pb (5.3-9.3) and Delta 8/4 Pb (46.3-68.1) values. They define a single trend of radiogenic lead enrichment from Celebes through Sulu to Cagayan Ridge, within the Indian Ocean MORB data field. The data suggest that the overall chemical and isotopic features of the Sulu, Cagayan and Celebes rocks may be explained by partial melting of a depleted asthenospheric N-MORB-type ("normal") mantle source with isotopic characteristics similar to those of the Indian Ocean MORB source. This asthenospheric source was slightly heterogeneous, giving rise to the Sr-Nd isotopic differences between the Celebes and Sulu basalts, and the Cagayan Ridge volcanics. In addition, a probably slab-derived component enriched in LILE and LREE is required to generate the elemental characteristics and low Ne(T) of the Cagayan Ridge island arc tholeiitic and calcalkaline lavas, and to contribute to a small extent in the backarc basalts of the Sulu Sea. The results of this study confirm and extend the widespread Indian Ocean MORB signature in the Western Pacifc region. This signature could have been inherited by the Indian Ocean mantle itself during the rupture of Gondwanaland, when fragments of this mantle could have migrated towards the present position of the Celebes, Sulu and Cagayan sources.

Advanced Adhesion Strength Testing Methods of Thin Film Multilayers in Electronic Packaging Systems

With the continued miniaturization and increasing performance of electronic devices, new technical challenges have arisen. One such issue is delamination occurring at critical interfaces inside the device. This major reliability issue can occur during the manufacturing process or during normal use of the device. Proper evaluation of the adhesion strength of critical interfaces early in the product development cycle can help reduce reliability issues and time-to-market of the product. However, conventional adhesion strength testing is inherently limited in the face of package miniaturization, which brings about further technical challenges to quantify design integrity and reliability. Although there are many different interfaces in today's advanced electronic packages, they can be generalized into two main categories: 1) rigid to rigid connections with a thin flexible polymeric layer in between, or 2) a thin film membrane on a rigid structure. Knowing that every technique has its own advantages and disadvantages, multiple testing methods must be enhanced and developed to be able to accommodate all the interfaces encountered for emerging electronic packaging technologies. For evaluating the adhesion strength of high adhesion strength interfaces in thin multilayer structures a novel adhesion test configuration called “single cantilever adhesion test (SCAT)” is proposed and implemented for an epoxy molding compound (EMC) and photo solder resist (PSR) interface. The test method is then shown to be capable of comparing and selecting the stronger of two potential EMC/PSR material sets. Additionally, a theoretical approach for establishing the applicable testing domain for a four-point bending test method was presented. For evaluating polymeric films on rigid substrates, major testing challenges are encountered for reducing testing scatter and for factoring in the potentially degrading effect of environmental conditioning on the material properties of the film. An advanced blister test with predefined area test method was developed that considers an elasto-plastic analytical solution and implemented for a conformal coating used to prevent tin whisker growth. The advanced blister testing with predefined area test method was then extended by employing a numerical method for evaluating the adhesion strength when the polymer’s film properties are unknown.