Endocytosis of the ASGP receptor H1 is reduced by mutation of tyrosine-5 but still occurs via coated pits

The clustering of plasma membrane receptors in clathrin-coated pits depends on determinants within their cytoplasmic domains. In several cases, individual tyrosine residues were shown to be necessary for rapid internalization. We have mutated the single tyrosine at position 5 in the cytoplasmic domain of the major subunit H1 of the asialoglycoprotein receptor to alanine. Expressed in fibroblasts cells, the mutant protein was accumulated in the plasma membrane, and its rate of internalization was reduced by a factor of four. The residual rate of endocytosis, however, was still significantly higher than that of resident plasma membrane proteins. Upon acidification of the cytoplasm, which specifically inhibits the formation of clathrin-coated vesicles but not uptake of the fluid phase marker Lucifer yellow, residual endocytosis was blocked. By immunoelectron microscopy mutant H1 could be directly demonstrated in coated pits. The fraction of wild-type and mutant H1 present in coated pits as determined by immunogold localization correlated well with the respective rates of internalization. Thus, mutation of tyrosine-5 only partially inactivates recognition of H1 for incorporation into coated pits

Effects of memory load and distraction on performance and event-related slow potentials in a visuospatial working memory task

Brain electrical activity related to working memory was recorded at 15 scalp electrodes during a visuospatial delayed response task. Participants (N = 18) touched the remembered position of a target on a computer screen after either a 1 or 8 sec delay. These memory trials were compared to sensory trials in which the target remained present throughout the delay and response periods. Distracter stimuli identical to the target were briefly presented during the delay on 30% of trials. Responses were less accurate in memory than sensory trials, especially after the long delay. During the delay slow potentials developed that were significantly more negative in memory than sensory trials. The difference between memory and sensory trials was greater at anterior than posterior electrodes. On trials with distracters, the slow potentials generated by memory trials showed further enhancement of negativity whereas there were minimal effects on accuracy of performance. The results provide evidence that engagement of visuospatial working memory generates slow wave negativity with a timing and distribution consistent with frontal activation. Enhanced brain activity associated with working memory is required to maintain performance in the presence of distraction. © 1997 by the Massachusetts Institute of Technolog

Stability of spontaneous, correlated activity in mouse auditory cortex

Neural systems can be modeled as networks of functionally connected neural elements. The resulting network can be analyzed using mathematical tools from network science and graph theory to quantify the system's topological organization and to better understand its function. While the network-based approach is common in the analysis of large-scale neural systems probed by non-invasive neuroimaging, few studies have used network science to study the organization of networks reconstructed at the cellular level, and thus many very basic and fundamental questions remain unanswered. Here, we used two-photon calcium imaging to record spontaneous activity from the same set of cells in mouse auditory cortex over the course of several weeks. We reconstruct functional networks in which cells are linked to one another by edges weighted according to the correlation of their fluorescence traces. We show that the networks exhibit modular structure across multiple topological scales and that these multi-scale modules unfold as part of a hierarchy. We also show that, on average, network architecture becomes increasingly dissimilar over time, with similarity decaying monotonically with the distance (in time) between sessions. Finally, we show that a small fraction of cells maintain strongly-correlated activity over multiple days, forming a stable temporal core surrounded by a fluctuating and variable periphery. Our work provides a careful methodological blueprint for future studies of spontaneous activity measured by two-photon calcium imaging using cutting-edge computational methods and machine learning algorithms informed by explicit graphical models from network science. The methods are easily extended to additional datasets, opening the possibility of studying cellular level network organization of neural systems and how that organization is modulated by stimuli or altered in models of disease.Comment: 15 pages, 3 figure

Two Photon Contribution to Polarization in K+→π+μ+μ−K^+ \rightarrow \pi^+ \mu^+ \mu^-

Short distance physics involving virtual top and charm quarks contributes to $\mu^+$ (and $\mu^-$) polarization in the decay $K^+ \rightarrow \pi^+ \mu^+ \mu^-$. Measurement of the parity violating asymmetry $(\Gamma_R - \Gamma_L)/(\Gamma_R + \Gamma_L)$, where $\Gamma_R$ and $\Gamma_L$ are the rates to produce right and left-handed $\mu^+$, may provide valuable information on the unitarity triangle. The parity violating asymmetry also gets a contribution from Feynman diagrams with two photon intermediate states. We estimate this two photon contribution to the asymmetry and discuss briefly the two photon contribution to time reversal odd asymmetries that involve both the $\mu^+$ and $\mu^-$ polarizations.Comment: (19 pages, 5 figures available on request. Uses phyzzx), CALT-68-1798, UCSD/PTH 92-2

Дослідження загальних тенденцій ринку ресторанного господарства України

Досліджено індустрію ресторанного бізнесу, темпи змін кількості підприємств ресторанного господарства за період 2005-2011 pp. Виявлено тенденції розвитку підприємств ресторанного господарства, динаміку стану галузі ресторанних послуг по регіонах України. Ключові слова: ресторанне господарство, динаміка, регіони України, розвиток, ресторанні мережі, кон’юнктура, ресторанний бізнес, функції ресторанного бізнесу.Исследована индустрия ресторанного бизнеса, темпы изменений количества предприятий ресторанного хозяйства за период с 2005 по 2011 г. Определены тенденции развития предприятий ресторанного хозяйства, состояния отрасли ресторанных услуг по регионам Украины. Ключевые слова: ресторанное хозяйство, динамика, регионы Украины, развитие, ресторанные сети, коньюнктура, ресторанный бизнес, функции ресторанного бизнеса.The industry of restaurant business and the rate of change in quantity of restaurants in 2005-2011 are investigated. The tendencies of development of enterprises of catering trade, and the state of restaurant services industryregardingthe regions of Ukraine are determined. Keywords: restaurant management, dynamics, regions of Ukraine, development, restaurant chains, conjuncture, restaurant business, functions of restaurant business, tendencies of development of restaurant business, dynamics of retail turnover

Стратегії та підходи до реструктуризації підприємств сфери ЖКГ в умовах реформування власності України

Наведено результати дослідження існуючих підходів до стратегічних напрямів реструктуризації підприємств сфери ЖКГ в умовах реформування власності. Ключові слова: стратегія реструктуризації, ЖКГ України, реструктуризація підприємства, антикризове управління, стратегічний менеджмент.Приведены результаты исследования существующих подходов в стратегических направлениях реструктуризации предприятий сферы ЖКГ в условиях реформирования собственности. Ключевые слова: стратегия реструктуризации, ЖКХ Украины, реструктуризация предприятия, антикризисное управление, стратегический менеджмент.The paper presents the results of studying the approaches in strategic directions of restructuring of housing and communal enterprises under property reformation in Ukraine. Keywords: strategy of restructuring, housing and communal facilities of Ukraine, restructuring of enterprise, anti-crisis management, strategic management

Strong ellipticity and spectral properties of chiral bag boundary conditions

We prove strong ellipticity of chiral bag boundary conditions on even dimensional manifolds. From a knowledge of the heat kernel in an infinite cylinder, some basic properties of the zeta function are analyzed on cylindrical product manifolds of arbitrary even dimension.Comment: 16 pages, LaTeX, References adde

Long-term antidepressant use: a qualitative study on perspectives of patients and GPs in primary care

Background Antidepressant use is often prolonged in patients with anxiety and/or depressive disorder(s) compared with recommendations in treatment guidelines to discontinue after sustained remission. Aim To unravel the motivations of patients and GPs causing long-term antidepressant use and to gain insight into possibilities to prevent unnecessary long-term use. Design and setting Qualitative study using semi-structured, in-depth interviews with patients and GPs in the Netherlands. Method Patients with anxiety and/or depressive disorder(s) (n = 38) and GPs (n = 26) were interviewed. Innovatively, the interplay between patients and their GPs was also investigated by means of patient-GP dyads (n = 20). Results The motives and barriers of patients and GPs to continue or discontinue antidepressants were related to the availability of supportive guidance during discontinuation, the personal circumstances of the patient, and considerations of the patient or GP. Importantly, dyads indicated a large variation in policies of general practices around long-term use and continuation or discontinuation of antidepressants. Dyads further indicated that patients and GPs seemed unaware of each other's (mismatching) expectations regarding responsibility to initiate discussing continuation or discontinuation. Conclusion Although motives and barriers to antidepressant continuation or discontinuation were related to the same themes for patients and GPs, dyads indicated discrepancies between them. Discussion between patients and GPs about antidepressant use and continuation or discontinuation may help clarify mutual expectations and opinions. Agreements between a patient and their GP can be included in a patient-tailored treatment plan