D-AKAP2, a novel protein kinase A anchoring protein with a putative RGS domain

Subcellular localization directed by specific A kinase anchoring proteins (AKAPs) is a mechanism for compartmentalization of cAMP-dependent protein kinase (PKA). Using a two-hybrid screen, a novel AKAP was isolated. Because it interacts with both the type I and type II regulatory subunits, it was defined as a dual specific AKAP or D-AKAP1. Here we report the cloning and characterization of another novel cDNA isolated from that screen. This new member of the D-AKAP family, D-AKAP2, also binds both types of regulatory subunits. A message of 5 kb pairs was detected for D-AKAP2 in all embryonic stages and in all adult tissues tested. In brain, skeletal muscle, kidney, and testis, a 10-kb mRNA was identified. In testis, several small mRNAs were observed. Therefore, D-AKAP2 represents a novel family of proteins. cDNA cloning from a mouse testis library identified the full length D-AKAP2. It is composed of 372 amino acids which includes the R binding fragment, residues 333-372, at its C-terminus. Based on coprecipitation assays, the R binding domain interacts with the N-terminal dimerization domain of RIalpha and RIIalpha. A putative RGS domain was identified near the N-terminal region of D-AKAP2. The presence of this domain raises the intriguing possibility that D-AKAP2 may interact with a Galpha protein thus providing a link between the signaling machinery at the plasma membrane and the downstream kinase.     

Long-term follow-up of a randomized post-induction therapy trial in acute myelogenous leukemia (a Southeastern Cancer Study Group trial)

A phase III clinical trial was designed to determine if more intensive induction and consolidation therapy for acute myeloblastic leukemia increases the remission rate and prolongs survival. A minor objective was to determine if the use of non-cross resistant drugs was more effective than the same drugs used for induction. Patients with untreated leukemia between the ages of 15 and 50 were given daunorubicin 45 mg/m2 for the first 3 days of a 10-day continuous infusion of cytosine arabinoside, initially at a dose of 2000 mg/m2 but reduced to 100 mg/m2 because of toxicity. Those under 36 achieving a complete remission and with an histocompatible donor were assigned to a transplant arm. The rest were randomized to receive one of three consolidation arms: A, cytosine arabinoside, 200 mg/m2 daily for 7 days and daunorubicin 45 mg/m2 daily for 3 days for three courses; B, one course as in Arm A followed by amsacrine, 120 mg/m2 daily for 5 days followed by a 5-day continuous infusion of azacytidine, 150 mg/m2/day; C, thioguanine and cytosine arabinoside, 100 mg/m2 every 12 h and daunorubicin 10 mg/m2 daily for 5 days for three courses followed by four maintenance courses of cytosine arabinoside, 100 mg/m2 daily for 5 days and daunorubicin, 45 mg/m2 for 2 days every 13 weeks. From 1981 to 1986, 398 eligible patients were enrolled and 219 achieved a complete remission. The initial induction dose of cytosine arabinoside was reduced after five of 29 patients exhibited fatal gastrointestinal toxicity. Only 11 patients were assigned to the transplant arm. There were no significant differences in the consolidation arms. The 5 year disease-free survivals were 38, 31 and 27% in arms A, B, and C respectively. Intensive consolidation therapy with the same or different drugs used in induction was as effective as lower dose consolidation followed by maintenance therapy.     

Modelling the three-dimensional elastic constants of parallel-fibred and lamellar bone

The complex hierarchical structure of lamellar bone makes understanding structure–mechanical function relations, very difficult. We approach the problem by first using the relatively simple structure of parallel-fibred bone to construct a mathematical model for calculating Young's moduli in three-dimensions. Parallel-fibred bone is composed essentially of arrays of mineralized collagen fibrils, which are also the basic structural motif of the individual lamellae of lamellar bone. Parallel-fibred bone structure has orthotropic symmetry. As the sizes and shapes of crystals in bone are not well known, the model is also used to compare the cases of platelet-, ribbon- and sheet-reinforced composites. The far more complicated rotated plywood structure of lamellar bone results in the loss of the orthotropic symmetry of individual lamellae. The mathematical model used circumvents this problem by sub-dividing the lamellar unit into a thin lamella, thick lamella, transition zone between them, and the recently observed back-flip lamella. Each of these is regarded as having orthotropic symmetry. After the calculation of their Young's moduli they are rotated in space in accordance with the rotated plywood model, and then the segments are combined to present the overall modulus values in three-dimensions. The calculated trends compare well with the trends in microhardness values measured for circumferential lamellar bone. Microhardness values are, as yet, the only measurements available for direct comparison. Although the model is not directly applicable to osteonal bone, which is composed of many hollow cylinders of lamellar bone, the range of calculated modulus values and the trends observed for off-axis calculations, compare well with measured values. © 1998 Chapman & Hall     

A thin film electrochromic display based on the tungsten bronzes

The main features of a passive thin film display cell based on the electrochemically reversible formation of a tungsten bronze according to the reaction

$\text{(colourless) WO}{}_3\text{+ x}\text{M}{}^{\mathrm{+}}\text{+ x}\text{e}{}^{\mathrm{?}}\text{?}\text{M}{}_{\mathrm{x}}\text{WO}{}_3\text{(blue)}$

where 0 < x < 1 are considered. Chemical analysis of an electrochemically coloured WO₃ film has confirmed the presence of M. It is shown that a critical requirement of these cells is that D_τ(qC_m/Q)² ≈ 1, where the symbols are, in order, the M⁺ diffusion coefficient, the required device response time, the electronic charge, the maximum practical volume concentration of M in the WO₃ film and lastly the area colouring charge. Typical energy requirements might be about 10 mJ cm^?2 per complete cycle in a favourable case.Ionic injection overpotentials and ionic diffusion both appear to play a significant role in determining cell currents. Preliminary diffusion coefficient results for Li⁺ in r.f. sputtered WO₃ films are reported, and their predicted dependence of film structure is discussed. The optical absorption of coloured WO₃ films is presented, and it is interpreted as being predominantly due to free-electron intraband transitions.     

Synthesis, structure, and field emission properties of sulfur-doped nanocrystalline diamond

The synthesis and properties of sulfur-doped nanocrystalline diamond films were investigated. The films were deposited by hot-filament chemical vapor deposition on Mo substrates using methane, hydrogen, and hydrogen disulfide. The nanocrystalline nature of the material arises from the induction of continuous secondary nucleation in the chemical vapor deposition environment. Complementary characterization tools were employed in order to obtain a comprehensive and coherent understanding of the correlations between the structural and electronic properties. In particular, sulfur-doped nanocrystalline diamond films show n-type Hall conductivity, enhanced field emission properties, and insensitivity to ion radiation. It was found that n-type doping of the tetragonally-bonded carbon matrix together with a nano network of trigonally-bonded carbon are crucial elements for enhanced field emission from nanocrystalline diamond. These conclusions and the corresponding supporting evidence are discussed.     

Roll‐to‐roll manufacturing considerations for flexible,cholesteric liquid‐crystal display (Ch‐LCD) media

Abstract— Roll‐to‐roll methods and equipment to manufacture a bistable, passively driven display media on a flexible substrate have been developed. Using continuous coating techniques and equipment, cholesteric liquid‐crystal droplets in a gelatin binder and a dark layer are simultaneously coated onto laser‐etched‐patterned transparent ITO conductors on a polymeric web. Second conductors are printed with a UV‐curable polymer thick‐film ink over the active display layers, followed by slitting and chopping to complete the manufacture of display media in a full roll‐to‐roll mode. Segmented‐ and matrix‐display media can be generated using these techniques. This paper will focus on the manufacturing considerations for producing matrix‐display media.     

Biomimetic Concealing of PLGA Microspheres in a 3D Scaffold to Prevent Macrophage Uptake

Scaffolds functionalized with delivery systems for the release of growth factors is a robust strategy to enhance tissue regeneration. However, after implantation, macrophages infiltrate the scaffold, eventually initiating the degradation and clearance of the delivery systems. Herein, it is hypothesized that fully embedding the poly(d,l ‐lactide‐co‐glycolide acid) microspheres (MS) in a highly structured collagen‐based scaffold (concealing) can prevent their detection, preserving the integrity of the payload. Confocal laser microscopy reveals that non‐embedded MS are easily internalized; when concealed, J774 and bone marrow‐derived macrophages (BMDM) cannot detect them. This is further demonstrated by flow cytometry, as a tenfold decrease is found in the number of MS engulfed by the cells, suggesting that collagen can cloak the MS. This correlates with the amount of nitric oxide and tumor necrosis factor‐α produced by J774 and BMDM in response to the concealed MS, comparable to that found for non‐functionalized collagen scaffolds. Finally, the release kinetics of a reporter protein is preserved in the presence of macrophages, only when MS are concealed. The data provide detailed strategies for fabricating three dimensional (3D) biomimetic scaffolds able to conceal delivery systems and preserve the therapeutic molecules for release.