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- Emre, C, et al.
(author)
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Age-related changes in brain phospholipids and bioactive lipids in the APP knock-in mouse model of Alzheimer's disease
- 2021
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In: Acta neuropathologica communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 9:1, s. 116-
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Journal article (peer-reviewed)abstract
- Sustained brain chronic inflammation in Alzheimer’s disease (AD) includes glial cell activation, an increase in cytokines and chemokines, and lipid mediators (LMs), concomitant with decreased pro-homeostatic mediators. The inflammatory response at the onset of pathology engages activation of pro-resolving, pro-homeostatic LMs followed by a gradual decrease. We used an APP knock-in (App KI) AD mouse that accumulates β-amyloid (Aβ) and presents cognitive deficits (at 2 and 6 months of age, respectively) to investigate LMs, their precursors, biosynthetic enzymes and receptors, glial activation, and inflammatory proteins in the cerebral cortex and hippocampus at 2-, 4-, 8- and 18-month-old in comparison with wild-type (WT) mice. We used LC-mass-spectrometry and MALDI molecular imaging to analyze LMs and phospholipids, and immunochemistry for proteins. Our results revealed an age-specific lipid and cytokine profile, and glial activation in the App KI mice. Despite an early onset of Aβ pathology, pro-inflammatory and pro-resolving LMs were prominently increased only in the oldest age group. Furthermore, the LM biosynthetic enzymes increased, and their receptor expression decreased in the aged App KI mice. Arachidonic acid (AA)-containing phospholipid molecular species were elevated, correlating with decreased cPLA2 activity. MALDI molecular imaging depicted differential distribution of phospholipids according to genotype in hippocampal layers. Brain histology disclosed increased microglia proliferation starting from young age in the App KI mice, while astrocyte numbers were enhanced in older ages. Our results demonstrate that the brain lipidome is modified preferentially during aging as compared to amyloid pathology in the model studied here. However, alterations in phospholipids signal early pathological changes in membrane composition.
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| 9. |
- Emre, C, et al.
(author)
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Intranasal delivery of pro-resolving lipid mediators rescues memory and gamma oscillation impairment in AppNL-G-F/NL-G-F mice
- 2022
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In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 245-
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Journal article (peer-reviewed)abstract
- Sustained microglial activation and increased pro-inflammatory signalling cause chronic inflammation and neuronal damage in Alzheimer’s disease (AD). Resolution of inflammation follows neutralization of pathogens and is a response to limit damage and promote healing, mediated by pro-resolving lipid mediators (LMs). Since resolution is impaired in AD brains, we decided to test if intranasal administration of pro-resolving LMs in the AppNL-G-F/NL-G-F mouse model for AD could resolve inflammation and ameliorate pathology in the brain. A mixture of the pro-resolving LMs resolvin (Rv) E1, RvD1, RvD2, maresin 1 (MaR1) and neuroprotectin D1 (NPD1) was administered to stimulate their respective receptors. We examined amyloid load, cognition, neuronal network oscillations, glial activation and inflammatory factors. The treatment ameliorated memory deficits accompanied by a restoration of gamma oscillation deficits, together with a dramatic decrease in microglial activation. These findings open potential avenues for therapeutic exploration of pro-resolving LMs in AD, using a non-invasive route.
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- Hageman, Isabel C., et al.
(author)
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A Quality Assessment of the ARM-Net Registry Design and Data Collection
- 2023
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In: Journal of Pediatric Surgery. - : Elsevier BV. - 0022-3468. ; 58:10, s. 1921-1928
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Journal article (peer-reviewed)abstract
- Background: Registries are important in rare disease research. The Anorectal Malformation Network (ARM-Net) registry is a well-established European patient registry collecting demographic, clinical, and functional outcome data. We assessed the quality of this registry through review of the structure, data elements, collected data, and user experience. Material and methods: Design and data elements were assessed for completeness, consistency, usefulness, accuracy, validity, and comparability. An intra- and inter-user variability study was conducted through monitoring and re-registration of patients. User experience was assessed via a questionnaire on registration, design of registry, and satisfaction. Results: We evaluated 119 data elements, of which 107 were utilized and comprised 42 string and 65 numeric elements. A minority (37.0%) of the 2278 included records had complete data, though this improved to 83.5% when follow-up elements were excluded. Intra-observer variability demonstrated 11.7% incongruence, while inter-observer variability was 14.7%. Users were predominantly pediatric surgeons and typically registered patients within 11–30 min. Users did not experience any significant difficulties with data entry and were generally satisfied with the registry, but preferred more longitudinal data and patient-reported outcomes. Conclusions: The ARM-Net registry presents one of the largest ARM cohorts. Although its collected data are valuable, they are susceptible to error and user variability. Continuous evaluations are required to maintain relevant and high-quality data and to achieve long-term sustainability. With the recommendations resulting from this study, we call for rare disease patient registries to take example and aim to continuously improve their data quality to enhance the small, but impactful, field of rare disease research. Level of Evidence: V.
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- Karlsson, Gunnar, et al.
(author)
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A Future Wireless Internet Beyond Generations
- 2010
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In: Proceedings of the 5th International Conference on Future Internet Technologies, CFI10. - New York, NY, USA : ACM. - 9781450302302 ; , s. 5-9
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Conference paper (peer-reviewed)abstract
- The use of licensed spectrum for wireless communication is driven by the need to control interference between operators. This regulation leads to inefficient utilization of spectrum and causes shortage of free spectrum that hinders the entry of new operators and introduction of new wireless technologies. In this work, we present an evolutionary model for which license-free operation is the spectrum sharing mode so that networks can be built freely by anyone and new technologies can be deployed as soon as they become available. The paradigm assumes users to have open access to all public networks without prior contracts with operators. Hence, freely roaming users will drive competition among wireless network access providers, who in turn can meet demand quickly by offering access at low price, high quality, in hitherto uncovered areas, and by means of novel superior technology. We present a straw-man design and discuss the inherent technical challenges that must be addressed.
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- Kovyrshin, Arseny, et al.
(author)
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Nonadiabatic Nuclear-Electron Dynamics: A Quantum Computing Approach
- 2023
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In: Journal of Physical Chemistry Letters. - 1948-7185. ; 14:31, s. 7065-7072
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Journal article (peer-reviewed)abstract
- Coupled quantum electron-nuclear dynamics is oftenassociatedwith the Born-Huang expansion of the molecular wave functionand the appearance of nonadiabatic effects as a perturbation. On theother hand, native multicomponent representations of electrons andnuclei also exist, which do not rely on any a priori approximation.However, their implementation is hampered by prohibitive scaling.Consequently, quantum computers offer a unique opportunity for extendingtheir use to larger systems. Here, we propose a quantum algorithmfor simulating the time-evolution of molecular systems and apply itto proton transfer dynamics in malonaldehyde, described as a rigidscaffold. The proposed quantum algorithm can be easily generalizedto include the explicit dynamics of the classically described molecularscaffold. We show how entanglement between electronic and nucleardegrees of freedom can persist over long times if electrons do notfollow the nuclear displacement adiabatically. The proposed quantumalgorithm may become a valid candidate for the study of such phenomenawhen sufficiently powerful quantum computers become available.
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- McKeith, IG, et al.
(author)
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Diagnosis and management of dementia with Lewy bodies - Third report of the DLB consortium
- 2005
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In: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 1526-632X .- 0028-3878. ; 65:12, s. 1863-1872
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Research review (peer-reviewed)abstract
- The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each individual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in similar to 50%, and improvements in attention, visual hallucinations, and sleep disorders with cholinesterase inhibitors.
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| 18. |
- Nykänen, Anton, et al.
(author)
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Toward Accurate Post-Born-Oppenheimer Molecular Simulations on Quantum Computers: An Adaptive Variational Eigensolver with Nuclear-Electronic Frozen Natural Orbitals
- 2023
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In: Journal of Chemical Theory and Computation. - 1549-9626 .- 1549-9618. ; 19:24, s. 9269-9277
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Journal article (peer-reviewed)abstract
- Nuclear quantum effects such as zero-point energy and hydrogen tunneling play a central role in many biological and chemical processes. The nuclear-electronic orbital (NEO) approach captures these effects by treating selected nuclei quantum mechanically on the same footing as electrons. On classical computers, the resources required for an exact solution of NEO-based models grow exponentially with system size. By contrast, quantum computers offer a means of solving this problem with polynomial scaling. However, due to the limitations of current quantum devices, NEO simulations are confined to the smallest systems described by minimal basis sets, whereas realistic simulations beyond the Born-Oppenheimer approximation require more sophisticated basis sets. For this purpose, we herein extend a hardware-efficient ADAPT-VQE method to the NEO framework in the frozen natural orbital (FNO) basis. We demonstrate on H2 and D2 molecules that the NEO-FNO-ADAPT-VQE method reduces the CNOT count by several orders of magnitude relative to the NEO unitary coupled cluster method with singles and doubles while maintaining the desired accuracy. This extreme reduction in the CNOT gate count is sufficient to permit practical computations employing the NEO method─an important step toward accurate simulations involving nonclassical nuclei and non-Born-Oppenheimer effects on near-term quantum devices. We further show that the method can capture isotope effects, and we demonstrate that inclusion of correlation energy systematically improves the prediction of difference in the zero-point energy (ΔZPE) between isotopes.
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- Yavuz, Emre A., et al.
(author)
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A practical method for estimating performance metrics of call admission control schemes in wireless mobile networks
- 2005
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In: 2005 IEEE Wireless Communications and Networking Conference, Vols 1-4. - 0780389662 ; , s. 1254-1259
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Conference paper (peer-reviewed)abstract
- Providing the desired call blocking probability to not only new but also existing calls has been a challenge for wireless mobile network service providers. To satisfy different requirements for new and handoff call blocking probabilities, several call admission control (CAC) schemes have been proposed in the literature. Exact analysis of these schemes using two dimensional Markov chain is computationally intensive. Therefore under specific assumptions computationally efficient methods to analyze these systems using one dimensional Markov chain models have been considered. The "traditional" approach assumes that channel holding time for new and handoff calls have equal mean values. While the "normalized" approach relaxes this assumption, it is accurate only for the new call bounding CAC scheme. In this paper, we reevaluate the analytical methods for computing call blocking probabilities for several widely known call admission control schemes under more general assumptions by providing an easy to implement method. The numerical results show that when the average values of channel holding times for new and handoff calls are different, the proposed approach gives more accurate results when compared with the traditional and normalized methods based on one dimensional Markov chain modeling, while keeping the computational complexity low.
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| 21. |
- Yavuz, Emre A., et al.
(author)
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Computationally efficient method to evaluate the performance of guard-channel-based call admission control in cellular networks
- 2006
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In: IEEE Transactions on Vehicular Technology. - 0018-9545 .- 1939-9359. ; 55:4, s. 1412-1424
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Journal article (peer-reviewed)abstract
- Many guard-channel-based call admission control (CAC) schemes for cellular networks have been proposed to provide the desired quality of service to not only new calls but also ongoing calls when they hand off to neighboring cells. Blocking/dropping probabilities of new/handoff calls are generally analyzed using one-dimensional Markov chain modeling under specific assumptions to avoid solving large sets of flow equations that makes exact analyses of these schemes using multidimensional Markov chain models infeasible. This is the case with the "traditional" approach, which assumes that channel holding times for new and handoff calls have equal mean values, and the "normalized" approach, which relaxes this assumption but is accurate only for the new call bounding CAC scheme. In this paper, we reevaluate the analytical methods for computing new/handoff call blocking/dropping probabilities for several widely known CAC schemes and develop an easy-to-implement method under more general assumptions. Numerical results show that when the mean channel holding times for new and handoff calls are different, the proposed "effective holding time" approach gives more accurate results compared with the traditional and the normalized methods while keeping the computational complexity low. The accuracy of these methods and their levels of computational complexity with the exact solution are also compared.
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| 22. |
- Yavuz, Emre A., et al.
(author)
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Efficient approximations for call admission control performance evaluations in multi-service networks
- 2006
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In: GLOBECOM 2006. - 9781424403561
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Conference paper (peer-reviewed)abstract
- Several dynamic call admission control (CAC) schemes for cellular networks have been proposed in the literature to reserve resources adaptively to provide the desired quality of service (QoS) to not only high priority calls but also to low priority ones. Efficient adaptive reservations depend on reliable and up-to-date system status feedback provided to the CAC mechanism. However exact analysis of these schemes using multidimensional Markov chain models are intractable in real time due to the need to solve large sets of flow equations. Hence performance metrics such as call blocking probabilities of various QoS classes are generally evaluated using one dimensional Markov chain models assuming that channel occupancy times for all QoS classes have equal mean values and all arriving calls have equal capacity requirements. In this paper we re-evaluate the analytical methods to compute call blocking probabilities of various QoS classes for several widely known CAC schemes by relaxing these assumptions, and propose a novel approximation method for performance evaluation with low computational complexity. Numerical results show that proposed method provides results that match well with the exact solutions.
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| 23. |
- Yavuz, Emre A., et al.
(author)
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Efficient Methods for Performance Evaluations of Call Admission Control Schemes in Multi-Service Cellular Networks
- 2008
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In: IEEE Transactions on Wireless Communications. - 1536-1276 .- 1558-2248. ; 7:9, s. 3468-3476
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Journal article (peer-reviewed)abstract
- Many dynamic call admission control (CAC) schemes have been proposed in the literature for adaptive reservations in cellular networks. Efficient application of these schemes requires reliable and up-to-date feedback of system performance to the CAC mechanism. However, exact analyses of these schemes in real time using multi-dimensional Markov chain models are challenging due to the need to solve large sets of flow equations. One dimensional Markov chain models have been widely used to derive performance metrics such as call blocking probabilities of multiple traffic classes assuming that all classes of calls have equal capacity requirements and exponentially distributed channel holding times with equal mean values. These assumptions need to be relaxed for a more general evaluation of CAC performance in multi-service cellular networks. In this paper we classify CAC schemes according to their Markov chain models into two categories: symmetric and asymmetric, and develop computationally efficient analytical methods to compute call blocking probabilities of various traffic classes for several widely known CAC schemes under relaxed assumptions. We obtain a product form solution to evaluate symmetric schemes and propose a novel performance evaluation approximation method with low computational cost for asymmetric schemes. Numerical results demonstrate the accuracy and efficiency of the proposed method.
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| 24. |
- Yavuz, Emre A., et al.
(author)
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Modelling channel occupancy times for voice traffic in cellular networks
- 2007
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In: 2007 IEEE INTERNATIONAL CONFERENCE ON COMMUNICATIONS, VOLS 1-14. - 9781424403523 ; , s. 332-337
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Conference paper (peer-reviewed)abstract
- Call holding times in telephony networks are commonly approximated by exponential distributions to facilitate traffic engineering. However, for traffic engineering of cellular networks, channel occupancy times need to be modeled instead to facilitate analytical modeling or to feed network simulations. In this paper, we classify channel occupancy times and present an empirical study based on data obtained from a real cellular network to determine which probability distribution functions can approximate them better. The results are environment dependent, but no assumptions that can be influential are made, as opposed to previous analytical and simulation studies which results are highly dependent on the assumptions made by the authors. We show that all types of channel occupancy times can be approximated by lognormal distribution. For stationary users, channel occupancy times are commonly approximated by exponential distribution due to its tractability, assuming that cell residence times are also exponentially distributed. However, we show that lognormal distribution fits much better to both channel occupancy and call holding times regardless of whether users are stationary or mobile.
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