Characterization of the immune response after local delivery of recombinant adenovirus in murine pancreas and successful strategies for readministration

The pancreas is an ideal organ for adenoviral gene therapy because of the high level of gene transfer that can be achieved and because of the many diseases that can potentially be treated using this technology. In this report, we characterize the immune response to direct pancreatic injection of adenovirus and we overcome some of the limitations it imposes by using immunosuppression. Direct injection of recombinant adenovirus into the pancreas leads to the production of neutralizing antibodies and to sensitized splenocytes which engage in increased cytotoxic, lymphoproliferative, and cytokine release activity when reexposed to adenovirus. Transgene expression is transient and the vector cannot be readministered. Deletion of CD4+ T helper cells improves expression over time (40% of pancreatic cells express transgene at day 28 vs. 5% in controls), and allows the vector to be readministered in the pancreas, albeit, inefficiently, when compared to naive animals. Similarly, blockade of CD40 ligand, which preserves the CD4+ T helper cell population, also improves expression over time (30% of pancreatic cells express transgene at day 28), and allows the vector to be readministered. With both approaches, neutralizing antibodies are decreased and the remaining splenocytes do not engage in activated immune responses. Thus, local delivery of the adenoviral vector induces a systemic response that prevents pancreatic readministration, even with direct injection. Blockade of CD40 ligand and T helper cell depletion are transient regimens that induce systemic immunosuppression. Until the development of newer strategies that selectively suppress adenoviral immune responses, these are viable alternatives for enhancement of pancreatic adenoviral delivery.     

Cardiac morphology and left ventricular function in normotensive morbidly obese patients with and without congestive heart failure, and effect of weight loss

BACKGROUND: Prevention of hypothermia during abdominal surgery by insulating or heat-transferring methods has been the subject of numerous investigations. This study approaches the problem from a less discussed point of view, i.e. the effect of different surgical techniques on body temperature changes. METHODS: Body temperature was measured at 3 core and 6 skin points in 40 patients scheduled for cholecystectomy through open laparotomy or laparoscopy with pneumoperitoneum created and maintained with unwarmed carbon dioxide (CO2) insufflation. End-tidal CO2 was kept constant by adjustments of respiratory frequency. Anaesthesia, intravenous infusions, and draping of the patients were standardized. RESULTS: During the first 1 h of anaesthesia core temperatures decreased approximately by 0.7 degrees C and distal skin temperatures increased by 7 degrees C in both groups. At the end of surgery heat balance was similar in both groups. An increase of 2.5 1.min-1 in respiratory minute volume was needed to control end-tidal CO2 levels in the laparoscopy group during pneumoperitoneum which was maintained with a CO2 flow of 1.2 1.min-1 through the abdominal cavity. CONCLUSION: Laparoscopic technique with unwarmed carbon dioxide insufflation does not offer any advantage in terms of body temperature changes when compared to open surgery.     

The importance of the Doppler angle

We examined 118 infrainguinal grafts (103 patients) to determine the effect changes in the angle of theta or Doppler angle had on the accuracy of velocity measurements made with a duplex scanner. Four separate measurements of peak velocity were made on each graft. Three measurements were made with the flow toward the probe at 60 degrees, 50 degrees, 120 degrees (60 degrees the other way). The probe was then turned 180 degrees so the flow was away from the probe and measurements were made at 60 degrees. When the primary cursor was aligned with the vessel wall (Technologist A), the mean velocity at 60 degrees was 69.4 cm/sec and 57.3 cm/sec at 50 degrees, a difference of 12 cm/sec. The same measurements done by Technologist B (primary cursor non aligned with the wall), showed a 10 cm/sec difference (60.7 and 50.5). We saw a consistent difference with even this small difference in the angle of theta throughout the study. The mean velocity obtained by Technologist A when the flow was toward the probe was 61.7. When the probe was turned 180 degrees (flow away from the probe), the mean velocity was 60.5. The same measurements by Technologist B were 51.8 and 50.5. This indicates that the direction of the flow of blood towards or away from the probe does not effect the velocity measurements. Using the vessel wall to line up the primary cursor provides a consistent and easily reproducible reference point to compare measurements made on different days but is less important for single measurements.     

Stability of Mullite Protective Coatings for Silicon-Based Ceramics

Silicon-based ceramics are prone to severe oxidation and volatilization problems in the presence of water vapor. To address these issues, mullite has been investigated in recent years as a possible protective coating material. To analyze the stability of such coatings, a multi-species diffusion model for ionic species is developed. Onsager reciprocity is assumed for the mobility coefficients and the resulting moving boundary problem is solved numerically. The formulation also accounts for substantial Si volatilization away from the outer surface of the coating. This model is used to analyze an initial transient leading to the formation of an internal silica layer, a second transient period that follows this silica formation, and a steady-state regime that can only be attained if Si diffusion is sufficiently fast.     

Nanocrystal-semiconductor interface: Atomic-resolution cross-sectional transmission electron microscope study of lead sulfide nanocrystal quantum dots on crystalline silicon

We report on a cross-sectional high resolution transmission electron microscope study of lead sulfide nanocrystal quantum dots （NCQDs） dispersed on electron-transparent silicon nanopillars that enables nearly atomically-resolved simultaneous imaging of the entire composite： the quantum dot, the interfacial region, and the silicon substrate. Considerable richness in the nanocrystal shape and orientation with respect to the substrate lattice is observed. The average NCQD-substrate separation is found to be significantly smaller than the length of the ligands on the NCQDs. Complementary photoluminescence measurements show that light emission from PbS NCQDs on silicon is effectively quenched which we attribute to intrinsic mechanisms of energy and charge transfer from PbS NCQDs to Si.     

Mixed convection in wall plumesConvection mixte dans les panaches parietauxErzwungene und freie konvektion bei wandauftriebsströmungenCмeшaннaя кoнвeкция в cвoБoднoкoнвeктивныч cтpyяч нa cтeнкe

An analysis is presented for mixed convection effects in a wall plume flow. The results apply downstream from the source. The method of matched asymptotic expansions has been used to obtain a consistent solution by simultaneously including both the effects of mixed convection and of higher order boundary layer corrections. Several subtle and interesting features of this flow arise and are explained. The unexpected role played by Prandtl number is clearly illustrated. For example, the effect of an aiding imposed forced flow is to reduce surface shear stress, for Pr = 0.7, and to increase it for Pr = 6.7. Further, it has been shown that such a Prandtl number effect on the surface shear stress is dependent on the kind of heating condition imposed at the surface. Results of numerical calculations are presented for two values of Prandtl number, 0.7 and 6.7, as characteristic of air and water, respectively. The overall effect of mixed convection on the downstream decay of surface temperature and on the maximum value of tangential velocity is seen to be greater in air than in water.     

Modelling of attenuation of Lamb waves using Rayleigh damping: Numerical and experimental studies

In this study, the Lamb mode attenuation constants were derived in terms of the attenuation coefficient, group velocity and central frequency of excitation of the Lamb mode, using the Rayleigh damping model. Attenuation of Lamb waves, both fundamental symmetric and anti-symmetric modes, propagating through viscoelastic media (cross-ply glass/epoxy laminate) was modelled using the Finite Element Method. Numerically simulated attenuation of Lamb waves using Lamb mode attenuation constants was found to be in good agreement with the assumed attenuation. Experiments were performed on a quasi-isotropic laminate, employing air-coupled ultrasonic transducers, to measure the attenuation coefficient. Lamb mode attenuation constants, computed using the attenuation coefficient, were used to model the attenuation of the Lamb mode in quasi-isotropic laminates. Numerically simulated amplitude variation was found to be in good agreement with that computed from experiments.     

ABC transporters Cdr1p, Cdr2p and Cdr3p of a human pathogen Candida albicans are general phospholipid translocators

We have used fluorescent 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD)-tagged phospholipid analogues, NBD-PE (phosphatidylethanolamine), NBD-PC (phosphatidylcholine) and NBD-PS (phosphatidylserine), to demonstrate that Cdr1p and its other homologues, Cdr2p and Cdr3p, belonging to the ATP-binding cassette (ABC) superfamily behave as general phospholipid translocators. Interestingly, CDR1 and CDR2, whose overexpression leads to azole resistance in C. albicans, elicit in-to-out transbilayer phospholipid movement, while CDR3, which is not involved in drug resistance, carries out-to-in translocation of phospholipids between the two monolayers of plasma membrane. Cdr1p, Cdr2p and Cdr3p could be further distinguished on the basis of their sensitivities to different inhibitors. For example, the in-to-out activity associated with Cdr1p and Cdr2p is energy-dependent and sensitive to sulphydryl blocking agents such as N-ethylmaleimide (NEM) and cytoskeleton disrupting agent cytochalasin E, while Cdr3p-associated out-to-in activity is energy-dependent but insensitive to NEM and cytochalasin E. We found that certain drugs, such as fluconazole, cycloheximide and miconazole, to which Cdr1p confers resistance could also affect in-to-out transbilayer movement of NBD-PE, while the same drugs had no effect on Cdr3p-mediated out-to-in translocation of NBD-PE. The ineffectiveness of these drugs to affect Cdr3p mediated out-to-in phospholipid translocation further confirms the inherent difference in the directionality of phospholipid translocation between these pumps. Notwithstanding the role of some of the Cdrps in drug resistance, this study clearly demonstrates that these ABC transporters of C. albicans are phospholipid translocators and this function could represent one of the physiological functions of such large family of proteins.     

Analysis of flange joints with elastic bolt

The contact zone and pressure distribution between two elastic plates joined by an elastic bolt and nut are estimated using finite element analysis. Smooth interfacial conditions are assumed in all the regions of contact. Eight node axisymmetric ring elements are used to model the structure. The matrix solution is obtained through frontal technique and this solution technique is shown to be very efficient for the iterative scheme adopted to determine the extent of contact. A parametric study is conducted varying the elastic properties of bolt and plate materials, bolt head diameter and thickness of the plates. The method of approach presented in this paper provides a solution with a realistic idealization of tension flange joints.     

5-GHz 32-bit integer execution core in 130-nm dual-V/sub T/ CMOS

A 32-bit integer execution core containing a Han-Carlson arithmetic-logic unit (ALU), an 8-entry /spl times/ 2 ALU instruction scheduler loop and a 32-entry /spl times/ 32-bit register file is described. In a 130 nm six-metal, dual-V/sub T/ CMOS technology, the 2.3 mm/sup 2/ prototype contains 160 K transistors. Measurements demonstrate capability for 5-GHz single-cycle integer execution at 25/spl deg/C. The single-ended, leakage-tolerant dynamic scheme used in the ALU and scheduler enables up to 9-wide ORs with 23% critical path speed improvement and 40% active leakage power reduction when compared to a conventional Kogge-Stone implementation. On-chip body-bias circuits provide additional performance improvement or leakage tolerance. Stack node preconditioning improves ALU performance by 10%. At 5 GHz, ALU power is 95 mW at 0.95 V and the register file consumes 172 mW at 1.37 V. The ALU performance is scalable to 6.5 GHz at 1.1 V and to 10 GHz at 1.7 V, 25/spl deg/C.