30 research outputs found
Heterogeneous and tissue-specific regulation of effector T cell responses by IFN-gamma during Plasmodium berghei ANKA infection.
No full textIFN-γ and T cells are both required for the development of experimental cerebral malaria during Plasmodium berghei ANKA infection. Surprisingly, however, the role of IFN-γ in shaping the effector CD4(+) and CD8(+) T cell response during this infection has not been examined in detail. To address this, we have compared the effector T cell responses in wild-type and IFN-γ(-/-) mice during P. berghei ANKA infection. The expansion of splenic CD4(+) and CD8(+) T cells during P. berghei ANKA infection was unaffected by the absence of IFN-γ, but the contraction phase of the T cell response was significantly attenuated. Splenic T cell activation and effector function were essentially normal in IFN-γ(-/-) mice; however, the migration to, and accumulation of, effector CD4(+) and CD8(+) T cells in the lung, liver, and brain was altered in IFN-γ(-/-) mice. Interestingly, activation and accumulation of T cells in various nonlymphoid organs was differently affected by lack of IFN-γ, suggesting that IFN-γ influences T cell effector function to varying levels in different anatomical locations. Importantly, control of splenic T cell numbers during P. berghei ANKA infection depended on active IFN-γ-dependent environmental signals--leading to T cell apoptosis--rather than upon intrinsic alterations in T cell programming. To our knowledge, this is the first study to fully investigate the role of IFN-γ in modulating T cell function during P. berghei ANKA infection and reveals that IFN-γ is required for efficient contraction of the pool of activated T cells
Conflictul artistic ca factor generator de subiect în trilogia lui Vasilii Diubin „Anca”
No full textWhen investigating the novel’s system of one or another writer, main themes of his works can be pointed out, to understand what problems inherent that time the writer describes. In this article, relying on Vasily Dubin’s novel trilogy “Anka”, the author investigates the development and resolution of the main plot-forming conflict.
The author proves that in trilogy of Vasiliy Diubin “Anca” the main plot-forming conflict is interpersonal artistic conflict caused by different ideological positions of the heroes. In all trilogy works (“Bronzovaea Kosa”, “Shtorm” and “Seinery uhodeat v more”) the combination of different types of secondary conflicts (poly-conflicts) are presented: military, social, ideological, love and others. In this research, when investigating the artistic conflict shown in trilogy of Vasiliy Diubin “Anka”, the author of article shows conditionality of “internal” and “external”
conflicts by changing the social formation. The article
notes that citing on novel’s form, Vasiliy Diubin raises
the problems inherent that time: the becoming of a new
socio-economic system, the formation of a new way of
farming, the defense of the fatherland from a foreign enemy. So, as studies show the real events and conflicts that took the form of an artistic conflict in the novel play the role of the exponent of author’s ideas
Lifetime Studies at Metrology Light Source and ANKA
No full textAbstract The Metrology Light Source (MLS), situated in Berlin (Germany) is an electron storage ring operating from 105 MeV to 630 MeV and is serving as the national primary radiation source standard from the near infrared to the extrem ultraviolet spectral region INTRODUCTION To provide users of synchrotron radiation with temporally stable experimental conditions, the lifetime τ of the stored beam with current I is a parameter of concern. This is valid for machines with a decaying beam such as ANKA and MLS, but as well for machines operated in top up mode such as BESSY II in Berlin. In 2012, the standard user operation at MLS yielded a lifetime of 3.5 hours at 150 mA beam current. Although reasonable due to the energy, this is a low value compared to 16 hours at ANKA and it would benefit the users of synchrotron radiation if it could be improved. THEORY There are two major loss mechanisms determining the lifetime of the electrons in an accelerator: The scattering of the electrons with residual gas atoms and the scattering of the electrons with other electrons within the bunch. The latter is known as the "Touschek effect", named after Bruno Touschek who first observed the effect at the small AdA electron-positron collider. The two contributions are called gas lifetime and Touschek lifetime respectively. The gas lifetime depends on the pressure P and a scattering cross section σ gas for particle losses, for which the interested reader is referred to The cross section itself is a function of the acceptance of the accelerator δ acc = Δp max /p 0 , while the pressure P depends in some respect on the beam current. The electrons in a bunch perform transverse betatron oscillations. Being an incoherent motion, this leads to * [email protected] Coulomb scattering. During the scattering process, transverse momentum gets transferred to longitudinal momentum. If the particles momentum deviation exceeds the momentum acceptance it will be lost. The resulting Touschek lifetime depends on the rate of scattering processes and therefore on the density within the bunch, i.e. on the bunch volume and the bunch current. Furthermore, it depends on the momentum acceptance with the power of three with σ x,y,s being the rms-bunch sizes and length and D(ξ) being a slowly varying function with respect to the acceptance δ acc . D also depends on the optical functions around the ring through ξ. The loss rates from Touschek effect and gas scattering add to the total loss rate 1/τ which can be measured. Multiplying the number of particles N (or the stored current I) to the Touschek lifetime τ T results in a constant: N · τ T = const. Therefore, when plotting I · τ for a Touschek dominated lifetime a constant can be expected with respect to current. Acceptance Touschek lifetime and gas lifetime depend on the acceptance of the accelerator. Two acceptances are important here, and whichever is the smallest is the limiting one: • RF-acceptance • Geometrical acceptance. The RF-acceptance δ acc,RF approximately depends on the applied cavity voltage V as [4] The geometrical acceptance depends on the minimal aperture of the vacuum chamber a(s) and the dimensions of the beam. For MLS a first order approximation considering only the horizontal plane is: with D x being the horizontal dispersion function. In the upper plot of Predictions In the lower part of EXPERIMENT In LIFETIME IMPROVEMENT The lifetime at MLS can be improved if the acceptance is only RF-limited even to larger voltages than 300 kV. To do so, the geometrical acceptance has to be improved. In order to find optics with an increased Touschek lifetime, brute force optics scans using a Fortran code were performed In Eq. 4, the horizontal dispersion function D x is in the denominator. By decreasing the dispersion function at the place with minimum aperture, the geometrical acceptance δ acc,geom can be improved. At MLS each quadrupole is powered independently. By tuning some quadrupoles of one family against the remaining ones of that family, the dispersion function was tuned to be zero at the septum. In The peak lifetime with respect to cavity voltage is now located at 500 kV, being the maximum applicable cavity voltage at the moment. In The total lifetime increase is as high as 80 %. By solely increasing the acceptance, and the change in optical functions, the lifetime would have been expected to increase by about 30 %. An explanation for the additional increase could be a strong halo around the beam due to intra-beam scattering. With this, the effect of leading the beam through the centre of the vacuum chamber at the septum could be explained as well. CONCLUSION AND OUTLOOK The theory of the Touschek effect describes the dependencies on energy and acceptance well. By understanding the different loss mechanisms and the methods to manipulate the different acceptances, it was possible to generate a new user optics with an by 80 % improved lifetime. To completely explain the total lifetime increase, further measurements are needed. To further increase the lifetime, alternate optics determined by optics scans will be tested ACKNOWLEDGMENT The authors like to thank Andreas Jankowiak (HZB) and Gerhard Ulm (PTB) for supporting this work. REFERENCES [1] R. Klein et al., Phys. Rev. ST-AB 11, 110701, 2008. [2] A.-S. Müller et al., "Energy Calibration Of The ANKA Storage Ring", Proceedings of EPAC 2004. [3] T. Goetsch, "Lifetime Studies at Metrology Light Source and Angströmquelle Karlsruhe" -Diploma Thesis, Karlsruhe Institut für Technologie, May 2013. [4] M. Sands, "The Physics Of Electron Storage Rings -An Introduction", National Technical Information Service, Springfield, Virginia, 1970. [5] J. le Duff, "Current And Current Density Limitations In Existing Electron Storage Rings", In: Nucl. Instr. and Meth. in Physics Research, 1985
Plasmodium attenuation: Connecting the dots between early immune responses and malaria disease severity
No full textSterile attenuation of Plasmodium parasites at the liver-stage either by irradiation or genetic modification, or at the blood-stage by chemoprophylaxis, has been shown to induce immune responses that can protect against subsequent wild-type infection. However, following certain interventions, parasite attenuation can be incomplete or non-sterile. Instead parasites are rendered developmentally stunted but still capable of establishing an acute infection. In experiments involving Plasmodium berghei ANKA, a model of experimental cerebral malaria, it has been observed that several forms of attenuated parasites do not induce cerebral pathology. In this perspective we collect evidence from studies on murine malaria in particular, and attempt to connect the dots between early immune responses and protection from severe cerebral disease, highlighting potential parallels to human infection
Cerebral malaria: why experimental murine models are required to understand the pathogenesis of disease.
No full textCerebral malaria is a life-threatening complication of malaria infection. The pathogenesis of cerebral malaria is poorly defined and progress in understanding the condition is severely hampered by the inability to study in detail, ante-mortem, the parasitological and immunological events within the brain that lead to the onset of clinical symptoms. Experimental murine models have been used to investigate the sequence of events that lead to cerebral malaria, but there is significant debate on the merits of these models and whether their study is relevant to human disease. Here we review the current understanding of the parasitological and immunological events leading to human and experimental cerebral malaria, and explain why we believe that studies with experimental models of CM are crucial to define the pathogenesis of the condition
Sleep and adult neurogenesis: Implications for cognition and mood
No full textThe hippocampal dentate gyrus plays a critical role in learning and memory throughout life, in part by the integration of adult born neurons into existing circuits. Neurogenesis in the adult hippocampus is regulated by numerous environmental, physiological and behavioral factors known to affect learning and memory. Sleep is also important for learning and memory. Here we critically examine evidence from correlation, deprivation, and stimulation studies that sleep may be among those factors that regulate hippocampal neurogenesis. There is mixed evidence for correlations between sleep variables and rates of hippocampal cell proliferation across the day, the year and the lifespan. There is modest evidence that periods of increased sleep are associated with increased cell proliferation or survival. There is strong evidence that disruptions of sleep exceeding 24h, by total deprivation, selective REM sleep deprivation, chronic restriction or fragmentation, significantly inhibit cell proliferation and in some cases neurogenesis. The mechanisms by which sleep disruption inhibits neurogenesis are not fully understood. Although sleep disruption procedures are typically at least mildly stressful, elevated adrenal corticosterone secretion is not necessary for this effect. However, procedures that prevent both elevated corticosterone and interleukin 1 signaling have been found to block the effect of sleep deprivation on cell proliferation. This result suggests that sleep loss impairs hippocampal neurogenesis by the presence of wake-dependent factors, rather than by the absence of sleep-specific processes. This would weigh against a hypothesis that regulation of neurogenesis is a function of sleep. Nonetheless, impaired neurogenesis may underlie some of the memory and mood effects associated with acute and chronic sleep disruptions
The inhibitory effect of sleep deprivation on cell proliferation in the hippocampus of adult mice is eliminated by corticosterone clamp combined with interleukin-1 receptor 1 knockout
No full textSleep and adult neurogenesis:Implications for cognition and mood
No full textThe hippocampal dentate gyrus plays a critical role in learning and memory throughout life, in part by the integration of adult born neurons into existing circuits. Neurogenesis in the adult hippocampus is regulated by numerous environmental, physiological and behavioral factors known to affect learning and memory. Sleep is also important for learning and memory. Here we critically examine evidence from correlation, deprivation, and stimulation studies that sleep may be among those factors that regulate hippocampal neurogenesis. There is mixed evidence for correlations between sleep variables and rates of hippocampal cell proliferation across the day, the year and the lifespan. There is modest evidence that periods of increased sleep are associated with increased cell proliferation or survival. There is strong evidence that disruptions of sleep exceeding 24h, by total deprivation, selective REM sleep deprivation, chronic restriction or fragmentation, significantly inhibit cell proliferation and in some cases neurogenesis. The mechanisms by which sleep disruption inhibits neurogenesis are not fully understood. Although sleep disruption procedures are typically at least mildly stressful, elevated adrenal corticosterone secretion is not necessary for this effect. However, procedures that prevent both elevated corticosterone and interleukin 1 signaling have been found to block the effect of sleep deprivation on cell proliferation. This result suggests that sleep loss impairs hippocampal neurogenesis by the presence of wake-dependent factors, rather than by the absence of sleep-specific processes. This would weigh against a hypothesis that regulation of neurogenesis is a function of sleep. Nonetheless, impaired neurogenesis may underlie some of the memory and mood effects associated with acute and chronic sleep disruptions
Superconductive Damping Wigglers for the CLIC Project
No full textThe CLIC damping ring requires wigglers with both high on-axis fields and short periods. The present design foresees a superconductive wiggler with a period length of 5 cm, a peak on-axis field of 2.5 T and a full aperture of 12 mm. In this paper we explore the performance improvements of the damping ring when these parameters are pushed to 2.7 T at a period length of 2 cm with the expense of a reduced aperture of 5 mm. A design for a prototype for testing the field quality of such a wiggler is presented in this paper and the possibility to test this wiggler with beam in the storage ring ANKA is described
