Eukaryotic translation initiation machinery can operate in a prokaryotic-like mode without eIF2

Unlike prokaryotes, a specialized eukaryotic initiation factor 2 (eIF2), in the form of the ternary complex eIF2*GTP*Met-tRNAiMet is utilized to deliver the initiator tRNA to the ribosome within all eukaryotic cells1. Phosphorylation of eIF2 is known to be central to the global regulation of protein synthesis under stress conditions and infection2. Another distinctive feature of eukaryotic translation is scanning of mRNA 5'-leaders, whose origin in evolution may be relevant to the appearance of eIF2 in eukaryotes. Translation initiation on the hepatitis C virus (HCV) internal ribosome entry site (IRES) occurs without scanning3,4. Whether these unique features of the HCV IRES account for the formation of the final 80S initiation complex is unknown. Here we show that the HCV IRES-directed translation can occur without either eIF2 or its GTPase activating protein eIF5. In addition to the general eIF2- and eIF5-dependent pathway of 80S complex assembly, the HCV IRES makes use of a prokaryotic-like pathway which involves eIF5B, the analogue of bacterial IF25,6, instead of eIF2. This switch from a eukaryotic-like mode of AUG selection to a "bacterial" one occurs when eIF2 is inactivated by phosphorylation, a way with which host cells counteract infection. The relative resistance of HCV IRES-directed translation to eIF2 phosphorylation may represent one more line of defense used by this virus against host antiviral responses and can contribute to the well known resistance of HCV to interferon based therapy

Estimates of mortality and population changes in England and Wales over the two World Wars

Almost one million soldiers from England and Wales died during the First and Second World War whilst serving in the British Armed Forces. Although many articles and books have been published that commemorate the military efforts of the British Armed Forces, data on the demographic aspects of British army losses remain fragmentary. Official population statistics on England and Wales have provided continuous series on the civilian population, including mortality and fertility over the two war periods. The combatant population and combatant mortality have not been incorporated in the official statistics, which shows large out-migration at the beginning and large in-migration towards the end of the war periods. In order to estimate the dynamics of the total population and its excess mortality, we introduce in this paper a model of population flows and mortality in times of war operations. The model can be applied to a detailed reconstruction of war losses, using various shapes of the input data. This enables us to arrive at detailed estimates of war-related losses in England and Wales during the two world wars. Our results agree with elements of data provided by prior studies.England, First World War, population estimates, Second World War, Wales

Caching-Aided Collaborative D2D Operation for Predictive Data Dissemination in Industrial IoT

Industrial automation deployments constitute challenging environments where moving IoT machines may produce high-definition video and other heavy sensor data during surveying and inspection operations. Transporting massive contents to the edge network infrastructure and then eventually to the remote human operator requires reliable and high-rate radio links supported by intelligent data caching and delivery mechanisms. In this work, we address the challenges of contents dissemination in characteristic factory automation scenarios by proposing to engage moving industrial machines as device-to-device (D2D) caching helpers. With the goal to improve reliability of high-rate millimeter-wave (mmWave) data connections, we introduce the alternative contents dissemination modes and then construct a novel mobility-aware methodology that helps develop predictive mode selection strategies based on the anticipated radio link conditions. We also conduct a thorough system-level evaluation of representative data dissemination strategies to confirm the benefits of predictive solutions that employ D2D-enabled collaborative caching at the wireless edge to lower contents delivery latency and improve data acquisition reliability

The role of CaMKII in cerebellar learning

The molecular mechanisms underlying learning and memory are conserved between primitive and higher organized organisms. Memory formation requires plasticity between synaptic connections, and Ca2+ serves as an essential second messenger in the regulation of this plasticity. Calcium-calmodulin dependent protein kinase II (CaMKII) detects the amplitude and frequency of the Ca2+ signal, and transforms this transient signal into a graded, long-lasting Ca2+ independent signal. Activated CaMKII phosphorylates itself and various other proteins, which eventually leads to enhancement of synaptic efficacy. Because of these unique properties, it is not surprising that the CaMKII knock- out mouse was the first mouse to be studied in the field of Neuroscience. Since then, its role in hippocampal plasticity and hippocampal learning and memory has been intensely studied. These studies were subsequently replicated for cortical areas, for which the molecular mechanisms are very similar as the hippocampus. The molecular mechanisms underlying cerebellar motor learning are markedly different compared to excitatory neurons of the forebrain. Influx of high amounts of calcium into cerebellar Purkinje cells results in synaptic weakening rather than strengthening. In this thesis we explored the possibility that CaMKII might be involved in this weakening process and in cerebellar motor learning

Analysis of Intelligent Vehicular Relaying in Urban 5G+ Millimeter-Wave Cellular Deployments

The capability of smarter networked devices to dynamically select appropriate radio connectivity options is especially important in the emerging millimeter-wave (mmWave) systems to mitigate abrupt link blockage in complex environments. To enrich the levels of diversity, mobile mmWave relays can be employed for improved connection reliability. These are considered by 3GPP for on-demand densification on top of the static mmWave infrastructure. However, performance dynamics of mobile mmWave relaying is not nearly well explored, especially in realistic conditions, such as urban vehicular scenarios. In this paper, we develop a mathematical framework for the performance evaluation of mmWave vehicular relaying in a typical street deployment. We analyze and compare alternative connectivity strategies by quantifying the performance gains made available to smart devices in the presence of mmWave relays. We identify situations where the use of mmWave vehicular relaying is particularly beneficial. Our methodology and results can support further standardization and deployment of mmWave relaying in more intelligent 5G+ "all-mmWave" cellular networks.Comment: 6 pages, 8 figures. The paper has been accepted for IEEE GLOBECOM 2019. Copyright may be transferred without notice, after which this version may no longer be accessibl

On the Temporal Effects of Mobile Blockers in Urban Millimeter-Wave Cellular Scenarios

Millimeter-wave (mmWave) propagation is known to be severely affected by the blockage of the line-of-sight (LoS) path. In contrast to microwave systems, at shorter mmWave wavelengths such blockage can be caused by human bodies, where their mobility within environment makes wireless channel alternate between the blocked and non-blocked LoS states. Following the recent 3GPP requirements on modeling the dynamic blockage as well as the temporal consistency of the channel at mmWave frequencies, in this paper a new model for predicting the state of a user in the presence of mobile blockers for representative 3GPP scenarios is developed: urban micro cell (UMi) street canyon and park/stadium/square. It is demonstrated that the blockage effects produce an alternating renewal process with exponentially distributed non-blocked intervals, and blocked durations that follow the general distribution. The following metrics are derived (i) the mean and the fraction of time spent in blocked/non-blocked state, (ii) the residual blocked/non-blocked time, and (iii) the time-dependent conditional probability of having blockage/no blockage at time t1 given that there was blockage/no blockage at time t0. The latter is a function of the arrival rate (intensity), width, and height of moving blockers, distance to the mmWave access point (AP), as well as the heights of the AP and the user device. The proposed model can be used for system-level characterization of mmWave cellular communication systems. For example, the optimal height and the maximum coverage radius of the mmWave APs are derived, while satisfying the required mean data rate constraint. The system-level simulations corroborate that the use of the proposed method considerably reduces the modeling complexity.Comment: Accepted, IEEE Transactions on Vehicular Technolog

Hover or Perch: Comparing Capacity of Airborne and Landed Millimeter-Wave UAV Cells

On-demand deployments of millimeter-wave (mmWave) access points (APs) carried by unmanned aerial vehicles (UAVs) are considered today as a potential solution to enhance the performance of 5G+ networks. The battery lifetime of modern UAVs, though, limits the flight times in such systems. In this letter, we evaluate a feasible deployment alternative for temporary capacity boost in the areas with highly fluctuating user demands. The approach is to land UAV-based mmWave APs on the nearby buildings instead of hovering over the area. Within the developed mathematical framework, we compare the system-level performance of airborne and landed deployments by taking into account the full operation cycle of the employed drones. Our numerical results demonstrate that the choice of the UAV deployment option is determined by an interplay of the separation distance between the service area and the UAV charging station, drone battery lifetime, and the number of aerial APs in use. The presented methodology and results can support efficient on-demand deployments of UAV-based mmWave APs in prospective 5G+ networks.Comment: Accepted to IEEE Wireless Communications Letters on July 20, 2020. Copyright may be transferred without further notice after which this version may become non-availabl

The 5′ untranslated region of Apaf-1 mRNA directs translation under apoptosis conditions via a 5′ end-dependent scanning mechanism

AbstractWe have previously shown that translation driven by the 5′ UTR of Apaf-1 mRNA is relatively efficient in the absence of m7G-cap, but no IRES is involved. Nevertheless, it may be speculated that a “silent” IRES is activated under apoptosis conditions. Here, we show that translation of the mRNA with the Apaf-1 5′ UTR is relatively resistant to apoptosis induced by etoposide when eIF4E is sequestered by 4E-BP and eIF4G is partially cleaved. However, translation under these conditions remains governed by 5′ end-dependent scanning. We hypothesize that the observed phenomenon is based on the intrinsic low cap-dependence of the Apaf-1 5′ UTR

Handling Spontaneous Traffic Variations in 5G+ via Offloading onto mmWave-Capable UAV `Bridges'

Unmanned aerial vehicles (UAVs) are increasingly employed for numerous public and civil applications, such as goods delivery, medicine, surveillance, and telecommunications. For the latter, UAVs with onboard communication equipment may help temporarily offload traffic onto the neighboring cells in fifth-generation networks and beyond (5G+). In this paper, we propose and evaluate the use of UAVs traveling over the area of interest to relieve congestion in 5G+ systems under spontaneous traffic fluctuations. To this end, we assess two inherently different offloading schemes, named routed and controlled UAV `bridging'. Using the tools of renewal theory and stochastic geometry, we analytically characterize these schemes in terms of the fraction of traffic demand that can be offloaded onto the UAV `bridge' as our parameter of interest. This framework accounts for the unique features of millimeter-wave (mmWave) radio propagation and city deployment types with potential line-of-sight (LoS) link blockage by buildings. We also introduce enhancements to the proposed schemes that significantly improve the offloading gains. Our findings offer evidence that the UAV `bridges' may be used for efficient traffic offloading in various urban scenarios.Comment: This work has been accepted for publication in the IEEE Transactions on Vehicular Technolog