Power Control in Two-Tier Femtocell Networks

In a two tier cellular network -- comprised of a central macrocell underlaid with shorter range femtocell hotspots -- cross-tier interference limits overall capacity with universal frequency reuse. To quantify near-far effects with universal frequency reuse, this paper derives a fundamental relation providing the largest feasible cellular Signal-to-Interference-Plus-Noise Ratio (SINR), given any set of feasible femtocell SINRs. We provide a link budget analysis which enables simple and accurate performance insights in a two-tier network. A distributed utility-based SINR adaptation at femtocells is proposed in order to alleviate cross-tier interference at the macrocell from cochannel femtocells. The Foschini-Miljanic (FM) algorithm is a special case of the adaptation. Each femtocell maximizes their individual utility consisting of a SINR based reward less an incurred cost (interference to the macrocell). Numerical results show greater than 30% improvement in mean femtocell SINRs relative to FM. In the event that cross-tier interference prevents a cellular user from obtaining its SINR target, an algorithm is proposed that reduces transmission powers of the strongest femtocell interferers. The algorithm ensures that a cellular user achieves its SINR target even with 100 femtocells/cell-site, and requires a worst case SINR reduction of only 16% at femtocells. These results motivate design of power control schemes requiring minimal network overhead in two-tier networks with shared spectrum.Comment: 29 pages, 10 figures, Revised and resubmitted to the IEEE Transactions on Wireless Communication

Non-random escape pathways from a broadly neutralizing human monoclonal antibody map to a highly conserved region on the hepatitis C virus E2 glycoprotein encompassing amino acids 412-423

A challenge for hepatitis C virus (HCV) vaccine development is to define epitopes that are able to elicit protective antibodies against this highly diverse virus. The E2 glycoprotein region located at residues 412-423 is conserved and antibodies to 412-423 have broadly neutralizing activities. However, an adaptive mutation, N417S, is associated with a glycan shift in a variant that cannot be neutralized by a murine but by human monoclonal antibodies (HMAbs) against 412-423. To determine whether HCV escapes from these antibodies, we analyzed variants that emerged when cell culture infectious HCV virions (HCVcc) were passaged under increasing concentrations of a specific HMAb, HC33.1. Multiple nonrandom escape pathways were identified. Two pathways occurred in the context of an N-glycan shift mutation at N417T. At low antibody concentrations, substitutions of two residues outside of the epitope, N434D and K610R, led to variants having improved in vitro viral fitness and reduced sensitivity to HC33.1 binding and neutralization. At moderate concentrations, a S419N mutation occurred within 412-423 in escape variants that have greatly reduced sensitivity to HC33.1 but compromised viral fitness. Importantly, the variants generated from these pathways differed in their stability. N434D and K610R-associated variants were stable and became dominant as the virions were passaged. The S419N mutation reverted back to N419S when immune pressure was reduced by removing HC33.1. At high antibody concentrations, a mutation at L413I was observed in variants that were resistant to HC33.1 neutralization. Collectively, the combination of multiple escape pathways enabled the virus to persist under a wide range of antibody concentrations. Moreover, these findings pose a different challenge to vaccine development beyond the identification of highly conserved epitopes. It will be necessary for a vaccine to induce high potency antibodies that prevent the formation of escape variants, which can co-exist with lower potency or levels of neutralizing activities

The genome of a tortoise herpesvirus (testudinid herpesvirus 3) has a novel structure and contains a large region that is not required for replication in vitro or virulence in vivo

Testudinid herpesvirus 3 (TeHV-3) is the causative agent of a lethal disease affecting several tortoise species. The threat that this virus poses to endangered animals is focusing efforts on characterizing its properties, in order to enable the development of prophylactic methods. We have sequenced the genomes of the two most studied TeHV-3 strains (1976 and 4295). TeHV-3 strain 1976 has a novel genome structure and is most closely related to a turtle herpesvirus, thus supporting its classification into genus Scutavirus, subfamily Alphaherpesvirinae, family Herpesviridae. The sequence of strain 1976 also revealed viral counterparts of cellular interleukin-10 and semaphorin, which have not been described previously in members of subfamily Alphaherpesvirinae. TeHV-3 strain 4295 is a mixture of three forms (m1, m2, and M), in which, in comparison to strain 1976, the genomes exhibit large, partially overlapping deletions of 12.5 to 22.4 kb. Viral subclones representing these forms were isolated by limiting dilution, and each replicated in cell culture comparably to strain 1976. With the goal of testing the potential of the three forms as attenuated vaccine candidates, strain 4295 was inoculated intranasally into Hermann's tortoises (Testudo hermanni). All inoculated subjects died, and PCR analyses demonstrated the ability of the m2 and M forms to spread and invade the brain. In contrast, the m1 form was detected in none of the organs tested, suggesting its potential as the basis of an attenuated vaccine candidate. Our findings represent a major step towards characterizing TeHV-3 and developing prophylactic methods against it. IMPORTANCE: Testudinid herpesvirus 3 (TeHV-3) causes a lethal disease in tortoises, several species of which are endangered. We have characterized the viral genome, and used this information to take steps towards developing an attenuated vaccine. We have sequenced the genomes of two strains (1976 and 4295), compared their growth in vitro, and investigated the pathogenesis of strain 4295, which consists of three deletion mutants. The major findings are: (i) TeHV-3 has a novel genome structure; (ii) its closest relative is a turtle herpesvirus; (iii) it contains interleukin-10 and semaphorin genes, the first time these have been reported in an alphaherpesvirus; (iv) a sizeable region of the genome is not required for viral replication in vitro or virulence in vivo; and (v) one of the components of strain 4295, which has a deletion of 22.4 kb, exhibits properties indicating that it may serve as the starting point for an attenuated vaccine

Comparative cervical profiles of adult and under-18 front-row rugby players: implications for playing policy

Objective To compare the cervical isometric strength, fatigue endurance and range of motion of adult and under-18 age-grade front-row rugby players to inform the development of a safe age group policy with particular reference to scrummaging.Design Cross-sectional cohort study.Setting ‘Field testing’ at Murrayfield stadium.Participants 30 high-performance under-18 players and 22 adult front-row rugby players.Outcome measures Isometric neck strength, height, weight and grip strength.Results Youth players demonstrated the same height and grip strength as the adult players; however, the adults were significantly heavier and demonstrated substantially greater isometric strength (p<0.001). Only two of the ‘elite’ younger players could match the adult mean cervical isometric strength value. In contrast to school age players in general, grip strength was poorly associated with neck strength (r=0.2) in front-row players; instead, player weight (r=0.4) and the number of years’ experience of playing in the front row (r=0.5) were the only relevant factors in multivariate modelling of cervical strength (R2=0.3).Conclusions Extreme forces are generated between opposing front rows in the scrum and avoidance of mismatch is important if the risk of injury is to be minimised. Although elite youth front-row rugby players demonstrate the same peripheral strength as their adult counterparts on grip testing, the adults demonstrate significantly greater cervical strength. If older youths and adults are to play together, such findings have to be noted in the development of age group policies with particular reference to the scrum

Media events and cosmopolitan fandom:"Playful nationalism' in the Eurovision Song Contest

Academic literature on media events is increasingly concerned with their global dimensions and the applicability of Dayan and Katz's (1992) theoretical concept in a post-national context. This paper contributes to this debate by exploring the Eurovision Song Contest as a global media event. In particular, we employ a perspective from 'inside the media event', drawing upon empirical material collected during the 2014 Eurovision final in Copenhagen and focusing on the experiences of fans attending the contest. We argue that the ESC as a media event is experienced by its fans as a cosmopolitan space, open and diverse, whereas national belonging is expressed in a playful way tied to the overall visual aesthetics of the contest. However, the bounded and narrow character of participation render this cosmopolitan space rather limited

Age-related differences in the neck strength of adolescent rugby players: A cross-sectional cohort study of Scottish schoolchildren

ObjectivesTo evaluate the neck strength of school-aged rugby players, and to define the relationship with proxy physical measures with a view to predicting neck strength.MethodsCross-sectional cohort study involving 382 rugby playing schoolchildren at three Scottish schools (all male, aged between 12 and 18 years). Outcome measures included maximal isometric neck extension, weight, height, grip strength, cervical range of movement and neck circumference.ResultsMean neck extension strength increased with age (p = 0.001), although a wide inter-age range variation was evident, with the result that some of the oldest children presented with the same neck strength as the mean of the youngest group. Grip strength explained the most variation in neck strength (R2 = 0.53), while cervical range of movement and neck girth demonstrated no relationship. Multivariable analysis demonstrated the independent effects of age, weight and grip strength, and the resultant model explained 62.1% of the variance in neck strength. This model predicted actual neck strength well for the majority of players, although there was a tendency towards overestimation at the lowest range and underestimation at the highest.ConclusionA wide variation was evident in neck strength across the range of the schoolchild-playing population, with a surprisingly large number of senior players demonstrating the same mean strength as the 12-year-old mean value. This may suggest that current training regimes address limb strength but not neck strength, which may be significant for future neck injury prevention strategies. Age, weight and grip strength can predict around two thirds of the variation in neck strength, however specific assessment is required if precise data is sought

Sequences of complete human cytomegalovirus genomes from infected cell cultures and clinical specimens

We have assessed two approaches to sequencing complete human cytomegalovirus (HCMV) genomes (236 kbp) in DNA extracted from infected cell cultures (strains 3157, HAN13, HAN20 and HAN38) or clinical specimens (strains JP and 3301). The first approach involved amplifying genomes from the DNA samples as overlapping PCR products, sequencing these by the Sanger method, acquiring reads from a capillary instrument and assembling these using the Staden programs. The second approach involved generating sequence data from the DNA samples by using an Illumina Genome Analyzer (IGA), processing the filtered reads by reference-independent (de novo) assembly, utilizing the resulting sequence to direct reference-dependent assembly of the same data and finishing by limited PCR sequencing. Both approaches were successful. In particular, the investigation demonstrated the utility of IGA data for efficiently sequencing genomes from clinical samples containing as little as 3 % HCMV DNA. Analysis of the genome sequences obtained showed that each of the strains grown in cell culture was a mutant. Certain of the mutations were shared among strains from independent clinical sources, thus suggesting that they may have arisen in a common ancestor during natural infection. Moreover, one of the strains (JP) sequenced directly from a clinical specimen was mutated in two genes, one of which encodes a proposed immune-evasion function, viral interleukin-10. These observations imply that HCMV mutants exist in human infections

Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family