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.     

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)     

Serotonin-4 receptor antagonists reverse cocaine-induced cardiac arrhythmia

CONTEXT: Adolescent smoking prevalence is tracked annually and has increased since 1991. In contrast, little is known about trends in smoking among college students, a group that has previously been more resistant to tobacco use than other young adults. OBJECTIVE: To examine changes in cigarette smoking among college students between 1993 and 1997 and among different types of students and colleges. DESIGN: Self-administered survey (Harvard School of Public Health College Alcohol Study). SETTING: One hundred sixteen nationally representative 4-year colleges. SUBJECTS: A total of 15103 randomly selected students in 1993 (70% response rate) and 14251 students in 1997 (60% response rate). MAIN OUTCOME MEASURES: Self-reports of cigarette smoking in the past 30 days and in the past year, age at smoking first cigarette, and number of attempts to quit. RESULTS: Over 4 years, the prevalence of current (30-day) cigarette smoking rose by 27.8%, from 22.3% to 28.5% (P<.001). The increase was observed in 99 of 116 colleges and was statistically significant (P<.05) in 27 (23%) of them. Current smoking increased across all student subgroups (defined by sex, race/ethnicity, and year in school) and in all types of colleges. Smoking is rising faster in public schools (from 22.0% to 29.3%) than in private schools (from 22.9% to 26.8%). Eleven percent of college smokers had their first cigarette and 28% began to smoke regularly at or after age 19 years, by which time most were already in college. Half of current smokers tried to quit in the previous year; 18% had made 5 or more attempts to quit. CONCLUSIONS: Cigarette use is increasing on campuses nationwide in all subgroups and types of colleges. Substantial numbers of college students are both starting to smoke regularly and trying to stop. National efforts to reduce smoking should be extended to college students.     

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.     

Identifying acute pulpalgia as a factor in TMD pain

An acute pulpalgia and temporomandibular disorders can produce many of the same symptoms. To illustrate identification of an acute pulpalgia as a component in TMD, the authors review the evaluation of 11 patients at a clinic that specializes in TMD treatment. During the evaluation, thermal testing and periodontal ligament anesthesia were used to identify the offending tooth. After receiving endodontic treatment or having the tooth extracted, patients reported either complete or partial relief of TMD symptoms. The authors provide questions that may help practitioners identify a tooth with an acute pulpalgia as a contributing factor to TMD symptoms and suggest a technique to confirm this diagnosis.     

Assessing declarative memory in schizophrenia using Wisconsin Card Sorting Test stimuli: the Paired Associate Recognition Test

The Paired Associate Recognition Test (PART) was developed to measure declarative memory using Wisconsin Card Sorting Test (WCST) stimuli, so that both tasks could be administered during functional neuroimaging to differentiate memory and executive function, and associated frontal and temporal lobe activation in schizophrenia. The current study was designed to compare PART and WCST performance in schizophrenic patients and to examine effects of medication and symptomatology. The PART, WCST, and standard declarative memory tasks were administered to 30 chronic schizophrenic patients and 30 matched healthy control subjects. Supporting task validity was the finding that patients were equally impaired on the PART and the WCST. Neuroleptics did not appear to affect performance. The effect of anticholinergic medication correlated negatively with WCST performance in a small subsample. Severity of schizophrenia-specific symptoms measured at intake on the Brief Psychiatric Rating Scale correlated negatively with performance on the WCST. These results support the application of the PART and WCST in future functional neuroimaging studies.