Identification of potent P2Y-purinoceptor agonists that are derivatives of adenosine 5'-monophosphate

1. A series of chain-extended 2-thioether derivatives of adenosine monophosphate were synthesized and tested as agonists for activation of the phospholipase C-linked P2Y-purinoceptor of turkey erythrocyte membranes, the adenylyl cyclase-linked P2Y-purinoceptor of C6 rat glioma cells, and the cloned human P2U-receptor stably expressed in 1321N1 human astrocytoma cells. 2. Although adenosine monophosphate itself was not an agonist in the two P2Y-purinoceptor test systems, eleven different 2-thioether-substituted adenosine monophosphate analogues were full agonists. The most potent of these agonists, 2-hexylthio AMP, exhibited an EC50 value of 0.2 nM for activation of the C6 cell receptor. This potency was 16,000 fold greater than that of ATP and was only 10 fold less than the potency of 2-hexylthio ATP in the same system. 2-hexylthio adenosine was inactive. 3. Monophosphate analogues that were the most potent activators of the C6 cell P2Y-purinoceptor were also the most potent activators of the turkey erythrocyte P2Y-purinoceptor. However, agonists were in general more potent at the C6 cell receptor, and potency differences varied between 10 fold and 300 fold between the two receptors. 4. Although 2-thioether derivatives of adenosine monophosphate were potent P2Y-purinoceptor agonists no effect of these analogues on the human P2U-purinoceptor were observed. 5. These results support the view that a single monophosphate is sufficient and necessary for full agonist activity at P2Y-purinoceptors, and provide insight for strategies for development of novel P2Y-purinoceptor agonists of high potency and selectivity.     

Laparoscopic cholecystectomy and gallbladder cancer: a diagnostic and therapeutic dilemma

The correct treatment strategy of patients with unsuspected gallbladder cancer undergoing laparoscopy, and the prevention of delayed diagnosis are current issues. We report a case of late diagnosis with umbilical metastasis and poor survival. A policy of careful inspection of the gallbladder and a cautious strategy in the case of gross alteration of its external morphology seems advisable during laparoscopic cholecystectomy. Although no agreement exists concerning the best treatment in the event of delayed diagnosis, the adopted strategy is contingent on patient status, disease stage and the possibility of performing appropriate follow-up.     

Coded differential space-time modulation for flat fading channels

In this paper, powerful coding techniques for differential space-time modulation (DSTM) over Rayleigh flat fading channels and noncoherent detection without channel state information at the receiver are investigated. In particular, multilevel coding, bit-interleaved coded modulation, and so-called hybrid coded modulation (HCM) are devised and compared. For improved noncoherent reception multiple-symbol differential detection (MSDD) is adapted to DSTM. In order to reduce the computational effort required for MSDD, a low-complexity version of MSDD is applied. Evaluating the ergodic channel capacity for the different schemes as appropriate performance measure, HCM with simplified MSDD is shown to offer a favorable tradeoff between complexity and achievable power efficiency. Simulation results employing turbo codes in properly designed HCM schemes confirm the predictions from information theory.     

High quality LTCC resonator for voltage-controlled oscillator

Design and technology of microwave conductor lines embedded in low-temperature cofired ceramic (LTCC) multilayer substrates are summarized with a focus on achieving the highest possible quality (Q) factor for a given line inductance. The work was initiated to test the integrability of base station voltage-controlled oscillators (VCOs) in ceramic multilayer substrates. This approach leads to a miniaturization of current versions by a factor of 2 to 4. However, base station specifications for phase noise and hence resonator Q are extremely demanding. Therefore, both the design and the processing technology were optimized. By choosing a twin-line design with two parallel lines vertically separated by a single LTCC layer, Q factors of 90 and 180 have been achieved for integrated 5.5 nH inductors at frequencies of 640 MHz and 1650 MHz, respectively. Application of this result to VCO modules in standard LTCC technology already yields low phase noise levels, e.g., -136 dBc/Hz at 100 kHz offset, which is suitable for base station applications. However, further noise reduction is expected from a dedicated high Q fabrication process that uses conventional via punching and filling steps to replace the ceramic material between the two lines by conductive silver paste. This raises the Q to 120 and 200, respectively, at the two frequencies and adds extra degrees of freedom to LTCC design for low-loss wireless solutions.     

Multiresolution Representation of 2D CSG Models

Multiresolution is currently one of the main schemes used in CAD modeling for representing objects, particularly when large-scale geometric data must be transferred interactively over a network, as in the case of collaborative design. Increasingly complex products and growing competition have turned design into a collaborative team effort. Furthermore, the widespread development of Internet viewers has also necessitated the transfer and display of large-scale CAD models over networks. In order to reduce the volume of transferred data, efforts have been made to transfer CSG (Constructive Solid Geometry) models rather than those based on B_rep (Boundary Representation). This paper presents an original new method for speeding up data transfer by using multiresolution CSG models at different levels of details (LOD). The multiresolution CSG algorithm generates a hierarchy of multiresolution CSG trees; at each level, the shape is further approximated and represented by a smaller number of CSG primitives. The paper analyzes the proposed algorithm, and demonstrates its feasibility.     

Temporal and spatial aspects of an environmental stimulus influence the dynamics of behavioral regulation of the Aplysia siphon-withdrawal response.

Exposure to turbulence, an environmental stimulus, produces behavioral adaptation in the Aplysia siphon-withdrawal response (SWR). The authors show that the duration and spatial extent of turbulence influence adaptation recovery. In terms of duration, recovery in whole animals and reduced preparations (tail, siphon, and CNS) was more rapid after longer exposures to turbulence (10 min) than after briefer exposures (10 s-5 min). In terms of spatial extent, recovery in reduced preparations was more rapid after diffuse turbulence (tail and siphon together) compared with focal turbulence (siphon alone). Furthermore, spatial extent and duration interact: Duration regulates recovery only when turbulence is diffuse. Results suggest that SWR adaptation reflects a composite of cellular processes, including short-term synaptic enhancement in L30 inhibitory interneurons. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tissue fixation security in transosseous rotator cuff repairs: a mechanical comparison of simple versus mattress sutures

The primary purpose of this investigation was to compare tissue fixation security by simple sutures versus mattress sutures in transosseous rotator cuff repair. These two repair techniques were each performed in 17 human cadaver shoulders, with two bone tunnels being used for the repair by two simple sutures and two other bone tunnels being used for the repair by one mattress suture. The repairs were loaded to failure in a servohydraulic materials test system. Rotator cuff repair by simple sutures was found to be significantly stronger than repair by mattress sutures (P = .0007). The average ultimate load to failure for the simple suture construct (189.62 N) was 39.72% greater than that for the mattress suture construct (135.71 N). Most of the failures occurred by suture breakage at the knot. Load-sharing by multiple suture tails and multiple knots in the simple suture configuration likely contributed to its superior strength characteristics compared with the mattress suture configuration.     

Microphase structure and calculations of the interphase in poly (styrene-b-methylphenylsiloxane) diblock copolymers: a comparative study from small-angle X-ray scattering,electron spectroscopic imaging and solid-state nuclear magnetic resonance

The microphase structure of a series of poly (styrene-b-methylphenylsiloxane) (PS-b-PMPS)-diblock copolymers with various compositions and molecular weights has been studied by small-angle X-ray scattering, electron spectroscopic imaging and solid-state nuclear magnetic resonance spectroscopy. This diblock copolymer system is miscible within a distinct range of temperature and molecular weight exhibiting an upper critical solution temperature. The three chosen methods which complement each other can be applied to the chemically unmodified model system. The results of the various measurements correlate to describe the microphase structure, the domain size and the interphase.     

Conserved features of TBE1 transposons in ciliated protozoa

BACKGROUND: Accessory function (AF) is one way antigen presenting cells generate sufficient secondary signals for optimal T-cell proliferation and IL-2 production. In general, alveolar macrophages (AM) are inferior accessory cells in comparison to monocytes whereas in sarcoidosis AF of AM is increased. METHODS: We compared the accessory index (AI) of AM and peripheral blood monocytes (PBM) of 41 patients with inactive sarcoidosis (SAR I, n = 12); active sarcoidosis with new or progressing symptoms (SAR II, n = 19), active sarcoidosis with spontaneous remission (SAR III, n = 10), tuberculosis (TB, n = 12), hypersensitivity pneumonitis (HP, n = 12), Wegener's disease (WD, n = 2), undefined alveolitis (UA, n = 8) and chronic obstructive pulmonary disease (COPD, n = 6) by employing the histoincompatibility-insensitive Jurkat cells as indicator cells. RESULTS: Compared with the controls (1.08 +/- 0.3) AMs of all groups but SAR I (AI: 0.96 +/- 0.42) exhibited significantly increased AIs (SAR II: 3.6 +/- 3.9; SAR III: 3.2 +/- 2.4; TB: 2.8 +/- 2.2; HP: 3 +/- 2; UA: 2.7 +/- 2.3; COPD: 3.1 +/- 2.2; p < 0.05 for all comparisons). Only in HP, AI of PBM was significantly increased compared with controls (3 +/- 1.5, 1.3 +/- 0.5, respectively; p < 0.001). Alveolar macrophages from patients with arcoidosis, TB, and HB express the costimulatory molecule CD80 on their surface and anti-CD80 antibodies inhibited the IL-2 release of Jurkat cells in this system to 59 +/- 27%. CONCLUSIONS: Our data demonstrate that AM from patients with various diseases have the capability to act as competent accessory cells and that the reported accessory function of these cells is at least in part mediated by the expression of CD80.