Separating stimulus-locked and unlocked components of the auditory event-related potential

A new method is evaluated for separating stimulus-locked and unlocked components of auditory event-related EEG activity. The new method uses a regression based subtraction procedure as a way to account for latency and amplitude variability within individual trials. It was applied using the oddball paradigm under conditions of active and passive listening and analyzed as spectral correlations (normalized differences) between post-stimulus epochs of standard, target or deviant stimulus conditions and silent pre-stimulus baseline activity. The regression-subtraction procedure accounted for a greater amount of variance than a method that uses linear subtraction alone. The major component of the response to auditory stimulation was an event-related synchronization in the delta and theta (2-4 Hz) frequency range. Event-related desynchronizations were also observed in the 10 Hz (alpha/mu) and in the 20-30 Hz (beta) frequency range. The regression based subtraction procedure provides better separation of stimulus-locked and unlocked components of event-related EEG activity then linear subtraction alone. Stimulus-locked and unlocked components show different patterns and topographies of effects related to attention and active discrimination. Studying both stimulus-locked and unlocked components of event-related EEG reactivity in the frequency domain provides a more comprehensive account of dynamic brain activity subserving auditory information processing.     

Anandamide transport

N-Arachidonylethanolamine (anandamide) is an endogenous agonist of the cannabinoid CB1 and CB2 receptors and displays many of the same receptor-mediated physiological effects as delta9-tetrahydrocannabinol (delta9-THC), the active component of marijuana. As with any neurotransmitter, there must be tight control of anandamide receptor-mediated signaling and a means of rapid removal of the molecule from the system. Thus, the process by which anandamide is transported into the cell for metabolism has been a topic of much interest and has been implicated as a potential drug target in the treatment of several disease states that are reported to have an association with the endocannabinoid system. In this review, we will discuss the current models proposed for the mechanism of anandamide transport, the progress that has been made in the development of compounds that specifically inhibit anandamide transport, the observed effects of anandamide transport inhibition in vivo, and finally, potential therapeutic applications of compounds that inhibit anandamide transport.     

在性病门诊对商业性性服务小姐身份确认标准的研究

目的 制定出性病门诊医生对商业性性服务小姐身份的确认标准,以便更准确地用乘数法来估计商业性性服务小姐基数。方法 访谈5名有经验的性病门诊医生,并总结出他们对商业性性服务小姐身份进行确认的初步依据和标准;再访谈10名商业性性服务小姐自愿者,以判定初步确认的标准的可信性及可行性,并对初步确认的标准进行修订;选取4家性病门诊医院,每家医院各2名医生对前来就诊的女性生殖道感染者,依据制定的标准判断其是否为商业性性服务小姐,并对判断结果进行一致性评价。结果 通过访谈制定出性病门诊医生对商业性性服务小姐身份确认的标准,该标准实测的一致性为91．18％,并获得该标准各条目的相对重要性。结论 本次制定出的性病门诊医生对商业性性服务小姐身份的确认标准是可靠、可行的。     

A leak quantification method using sulfur hexafluoride as tracer gas

Filter holders and continuous air monitors are used extensively in the nuclear industry. It is important to minimize leakage in these devices, and, in recognition of this consideration, a limit on leakage for sampling systems is specified in; however, the protocol given in the standard is really germane to measurement of significant leakage, e.g., several percent of the sampling flow rate. In the present study, we developed a technique for quantifying leakage and used that approach to measure the sealing integrity of a continuous air monitor and two kinds of filter holders. The methodology involves use of sulfur hexafluoride as a tracer gas with the device being tested operated under dynamic flow conditions. The leak rates in these devices were determined in the pressure range from 2.49 kPa (10 inches H2O) vacuum to 2.49 kPa (10 inches H2O) pressure at a flow rate of 56.6 L min-1 (2 cfm). For the two filter holders, the leak rates were less than 0.007% of the nominal flow rate. The leak rate in the continuous air monitors was less than 0.2% of the nominal flow rate. These values are well within the limit prescribed in the ANSI standard, which is 5% of the nominal flow rate. We suggest that the limit listed in the ANSI standard should be reconsidered as lower values can be achieved, and the methodology presented herein can be used to quantify lower leakage values in sample collectors and analyzers.     

A novel sporadic mutation in cytochrome c oxidase subunit II as a cause of rhabdomyolysis

Disorders of the mitochondrial genome are an important cause of neurological disease, with patients presenting a variety of different phenotypes. Exercise induced muscle pain and myoglobinuria have been described with a number of metabolic defects, but because of the enormous variability of the mitochondrial genome identifying causative mitochondrial DNA mutations can be extremely difficult. Since mitochondrial tRNA genes were considered to be hot spots for mutation, sequencing was initially often confined to these genes. In a patient with symptoms and signs of exercise intolerance and myoglobinuria we originally ascribed pathogenicity to a mitochondrial-tRNA(Phe) mutation but here we show that the true pathogenic mutation was a novel mutation in the gene encoding subunit II of cytochrome c oxidase. We believe that this study demonstrates the importance of whole mitochondrial genome sequencing and of access to large sequence databases.     

Catastrophic presentation of mitochondrial disease due to a mutation in the tRNA(His) gene

The authors describe a patient who presented with headache, seizures, and severe cerebral edema in whom they identified a novel mutation in the mitochondrial (mt-) tRNA(His) gene. This G12147A transition is heteroplasmic, predicted to disrupt a highly conserved base pair, and segregates with the cytochrome c oxidase deficiency in single muscle fibers.     

Binding interactions between peptides and proteins of the class II major histocompatibility complex

The activation of helper T cells by peptides bound to proteins of the class II Major Histocompatibility Complex (MHC II) is pivotal to the initiation of an immune response. The primary functional requirement imposed on MHC II proteins is the ability to efficiently bind thousands of different peptides. Structurally, this is reflected in a unique architecture of binding interactions. The peptide is bound in an extended conformation within a groove on the membrane distal surface of the protein that is lined with several pockets that can accommodate peptide side-chains. Conserved MHC II protein residues also form hydrogen bonds along the length of the peptide main-chain. Here we review recent advances in the study of peptide-MHC II protein reactions that have led to an enhanced understanding of binding energetics. These results demonstrate that peptide-MHC II protein complexes achieve high affinity binding from the array of hydrogen bonds that are energetically segregated from the pocket interactions, which can then add to an intrinsic hydrogen bond-mediated affinity. Thus, MHC II proteins are unlike antibodies, which utilize cooperativity among binding interactions to achieve high affinity and specificity. The significance of these observations is discussed within the context of possible mechanisms for the HLA-DM protein that regulates peptide presentation in vivo and the design of non-peptide molecules that can bind MHC II proteins and act as vaccines or immune modulators.     

Low socioeconomic status is associated with a higher rate of death in the era of highly active antiretroviral therapy,San Francisco

Highly active antiretroviral therapy (HAART) has dramatically improved survival after AIDS. The benefits of HAART have not been equally realized for all communities, however. We characterize the association of socioeconomic status (SES) with survival after AIDS diagnosis in San Francisco in the period before (1980-1995) and after (1996 - 2001) the wider use of HAART. Using citywide surveillance data, we examined differences in survival after AIDS diagnosis by neighborhood household income using Kaplan-Meier survival analysis and Cox proportional hazards analysis to adjust for significant covariates. Residing in higher SES neighborhoods significantly predicted better survival after AIDS from 1996 to 2001 (hazard ratio = 0.92 per $10,000 increase in neighborhood household income, 95% CI: 0.85-0.99) after adjusting for CD4 count at diagnosis, age, and injection drug user status. Persons living in poorer neighborhoods were less likely to use HAART at any time in the past compared with persons in wealthier neighborhoods. Moreover, no association between survival and neighborhood SES was evident in the era prior to the wide use of HAART. Finally, the difference in survival by neighborhood income level disappeared after controlling for the use of HAART, suggesting that use of or access to treatment explained the association. From 1996 to 2001, survival with AIDS was worse for people living in poorer neighborhoods compared with those living in wealthier neighborhoods of San Francisco as a result of unequal access to or use of HAART.