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The Fourth Amendment is a mirage. On paper--in the rules studied by law students, analyzed by scholars, and proclaimed by jurists--its limitations are many and, oftentimes, significant. Yet the experience of large numbers of Americans is entirely to the contrary, thanks to the rights-annihilating, under-theorized exception of "consent." Under its guise, law enforcement officers routinely conduct what would otherwise be constitutionally-restrained searches and seizures, and they do so without meaningful explanation or assent. Fortunately, change--whether legislative or (ideally) constitutional--could be straightforward. Thanks to other sufficient triggers, consent could be replaced by a narrow, rights-protective doctrine under which law enforcement could continue to accomplish its aims--and in a more fair and evenhanded manner--and that would produce public data that could be mined for evidence of bias or manipulation. In this Article, then, we make the case for the abolition of Fourth Amendment consent except as an emergency doctrine, a move that would improve policing and restore an intended measure of human dignity and autonomy to the people. [ABSTRACT FROM AUTHOR]

Lateral intrusions flowing from the boundaries of lakes and oceans might influence basin‐scale distributions of heat, chemical solutes, sediments, and organisms. Here, observations of numerous intrusions from multiple locations in a small lake were used to examine the relation of intrusions to a lakewide internal seiche, and to estimate mean exchange between sloping bottom boundary layers (BBLs) and the lake interior. BBL waters were observed periodically separating from the bed and flowing laterally offshore. Boundary layer separation was initiated where strong downslope flows encountered upslope‐propagating temperature fronts. These separation events propagated upslope, coherent with the vertically propagating internal seiche, resembling previously reported cases of upslope‐propagating internal bores. Following separation, jets flowed offshore immediately above temperature fronts, transporting boundary layer water at least 61 m into the interior. Jet propagation could be traced upwards, from the bed at 9.4 m depth to the base of the surface mixed layer. Mean offshore transport was most intense within the metalimnion (4–7 m depth). Intruding intermediate‐temperature thermocline water was likely supplied both by river inputs and by boundary mixing of cold and warm waters. These findings suggest that periodic jets, resulting from seiche‐induced boundary layer separation, transported significant quantities of water from the boundary layer toward the stratified lake interior, with possible implications for distributions of sediments, solutes, and organisms. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV)-associated cervical cancer is a leading cause of cancer deaths in women. Here we present an integrated multi-omic analysis of 643 cervical squamous cell carcinomas (CSCC, the most common histological variant of cervical cancer), representing patient populations from the USA, Europe and Sub-Saharan Africa and identify two CSCC subtypes (C1 and C2) with differing prognosis. C1 and C2 tumours can be driven by either of the two most common HPV types in cervical cancer (16 and 18) and while HPV16 and HPV18 are overrepresented among C1 and C2 tumours respectively, the prognostic difference between groups is not due to HPV type. C2 tumours, which comprise approximately 20% of CSCCs across these cohorts, display distinct genomic alterations, including loss or mutation of the STK11 tumour suppressor gene, increased expression of several immune checkpoint genes and differences in the tumour immune microenvironment that may explain the shorter survival associated with this group. In conclusion, we identify two therapy-relevant CSCC subtypes that share the same defining characteristics across three geographically diverse cohorts. Human papillomavirus (HPV) is a known cause of cervical cancer. Here, the authors perform a multi-omic analysis using published cervical squamous cell carcinoma cohorts from the USA, Europe, and SubSaharan Africa and identify two cervical squamous cell carcinoma subtypes that display prognostic differences. [ABSTRACT FROM AUTHOR]

Methane (CH4) produced in anoxic sediments plays a significant role in the carbon economy of many lakes and reservoirs. CH4 released from sediments first crosses the bottom boundary layer (BBL), the layer of water overlying the lakebed where currents are slowed by friction with the sediments below. Physical and biogeochemical conditions in the BBL, which can fluctuate hourly to daily with basin‐wide internal waves (seiches), likely influence CH4 transport from sediments into the hypolimnion. In this study, we estimated CH4 fluxes across the BBL of a eutrophic lake using a novel in situ flux gradient approach adapted from marine applications. For 2–6 h periods throughout the spring and summer, we estimated CH4 fluxes across the BBL using simultaneous measurements of CH4 concentrations, turbulent mixing, and thermal stratification. Sub‐daily variation in CH4 fluxes was high, and CH4 fluxes sometimes changed several‐fold within hours. These rapid shifts in BBL fluxes were likely influenced by fluctuations in seiche‐driven variations in the intensity of BBL turbulent mixing. Fluxes increased from spring to summer, concurrent with the development of lake stratification, and fueled an accumulation of CH4 below the thermocline. Throughout the summer, CH4 flux across the BBL exceeded CH4 accumulation below the thermocline, suggesting significant methanotrophy in the hypolimnion, consistent with incubation‐based oxidation rates. Our results are the first to demonstrate sub‐daily and seasonal variability in the timing and magnitude of CH4 fluxes within a lake BBL, and highlight a need to quantify such variability in other lentic systems. [ABSTRACT FROM AUTHOR]

The last decade has brought tremendous change to the Fourth Amendment, finally resulting in a 'digital is different' norm. We stand at an inflection point between a monolithic, analog past and a murky future ofyet-unarticulated constitutional digital policing rules. It is a good time, then, to reflect upon how we came to be here and where we ought to go. This Essay.first looks back to a monumental, majestic dissent: that OfJustice Louis Brandeis in the 1928 decision ofOlmstead v. United States. Every American, and especially every law student, ought to know that opinion, and judges and scholars ought to appreciate how it charted the path we have now trod. The Essay then turns forward, considering whether we are finally ready for a longstanding Supreme Court assertion that has never been honestly applied: a Fourth Amendment warrant default. Given ubiquitous digital data, a warrant standard will often be required for searches to be reasonable. And, even when it is not-when the needs of effective investigation and resulting safety outweigh privacy and liberty concerns-the modern Fourth Amendment space is uniquely well situated to a 'penalty default' in which the State shoulders the burden of convincing legislators and then courts that such lesser standard is constitutionally correct. [ABSTRACT FROM AUTHOR]

In a stratified lake, where an internal seiche maintained an oscillating bottom boundary layer (BBL), processes including strain‐induced periodic stratification (SIPS), a downslope mean flow, and upslope‐propagating internal waves controlled fluctuating BBL mixing rates. To investigate these processes, high‐resolution temperature and velocity profiles were measured within 2 m of the sloping bed, through more than 100 cycles of upslope and downslope flows. The associated seiche‐induced velocity reversals coincided with the arrival of upslope‐propagating cold fronts. Although fronts are sometimes associated with internal wave breaking, in this lake the measured frontal slopes were small and breaking did not occur. When fronts were not propagating past instruments, near‐bed stratification was consistent with SIPS, being intensified by downslope flows and reduced by upslope flows. Owing to a downslope near‐bed mean flow, which was previously shown to cancel an upslope internal‐wave Stokes drift, peak downslope velocities regularly exceeded peak upslope velocities. Given these strong downslope velocities, turbulent dissipation rates were most intense during downslope phases. Therefore, during downslope flow, creation of stratification by SIPS coincided with elevated dissipation, creating conditions for effective mixing. Correspondingly, two simple parameterizations for mixing efficiency suggest that most of the total near‐bed buoyancy flux (≥ 82%), and most of the irreversible flux (87%), occurred during the downslope‐flow phase of internal seiche cycles. The observed mechanism for dominant mixing during downslope flow has potential to act in other environments where internal waves propagate up sloping beds. [ABSTRACT FROM AUTHOR]

T‐bet is the lineage‐specifying transcription factor for CD4+ TH1 cells. T‐bet has also been found in other CD4+ T cell subsets, including TH17 cells and Treg, where it modulates their functional characteristics. However, we lack information on when and where T‐bet is expressed during T cell differentiation and how this impacts T cell differentiation and function. To address this, we traced the ontogeny of T‐bet‐expressing cells using a fluorescent fate‐mapping mouse line. We demonstrate that T‐bet is expressed in a subset of CD4+ T cells that have naïve cell surface markers and transcriptional profile and that this novel cell population is phenotypically and functionally distinct from previously described populations of naïve and memory CD4+ T cells. Naïve‐like T‐bet‐experienced cells are polarized to the TH1 lineage, predisposed to produce IFN‐γ upon cell activation, and resist repolarization to other lineages in vitro and in vivo. These results demonstrate that lineage‐specifying factors can polarize T cells in the absence of canonical markers of T cell activation and that this has an impact on the subsequent T‐helper response. [ABSTRACT FROM AUTHOR]

A young defense attorney earns his client, charged in federal court with bank robbery, a jury acquittal. (It's the attorney's first.) One would expect the impartial judge to thank the jury for its service. Instead, this one harangues both jury and defense attorney ("entailing changes in his complexion from red to purple to dead white"), publicly rails against the verdict, attempts to bar the jurors from future service, refuses to release the defendant, and successfully prods prosecutors to bring a duplicative state prosecution that would end in conviction for the same crime. To anyone who respects the rule of law--or at the very least to anyone who respects the American jury--this should be deeply troubling. Yet when it took place in a Chicago federal courtroom in December 1953, state prosecutors leapt at the federal judge's call. And when the appeal of the duplicative state prosecution reached the United States Supreme Court, the defendant lost 5-4. Criminal practitioners know that result as Bartkus v. Illinois, 359 U.S. 121 (1959), a rule of double-jeopardy "dual sovereignty" that the Court reaffirmed in 2019. But next to nobody appreciates how it began in that Chicago federal courtroom. That history comes to life in the unpublished notes of the remarkable defense lawyer. It is a story that underscores just how wrongheaded is the legal rule, and that makes vivid the abuse of judicial power. [ABSTRACT FROM AUTHOR]

The PAF complex (PAFC) coordinates transcription elongation and mRNA processing and its CDC73/parafibromin subunit functions as a tumour suppressor. The NF2/Merlin tumour suppressor functions both at the cell cortex and nucleus and is a key mediator of contact inhibition but the molecular mechanisms remain unclear. In this study we have used affinity proteomics to identify novel Merlin interacting proteins and show that Merlin forms a complex with multiple proteins involved in RNA processing including the PAFC and the CHD1 chromatin remodeller. Tumour-derived inactivating mutations in both Merlin and the CDC73 PAFC subunit mutually disrupt their interaction and growth suppression by Merlin requires CDC73. Merlin interacts with the PAFC in a cell density-dependent manner and we identify a role for FAT cadherins in regulating the Merlin-PAFC interaction. Our results suggest that in addition to its function within the Hippo pathway, Merlin is part of a tumour suppressor network regulated by cell-cell adhesion which coordinates post-initiation steps of the transcription cycle of genes mediating contact inhibition. [ABSTRACT FROM AUTHOR]

Within a wave‐exposed mangrove forest, novel field observations are presented, comparing millimeter‐scale turbulent water velocity fluctuations with contemporaneous subtidal bed elevation changes. High‐resolution velocity and bed level measurements were collected from the unvegetated mudflat, at the mangrove forest fringe, and within the forest interior over multiple tidal cycles (flood–ebb) during a 2‐week period. Measurements demonstrated that the spatial variability in vegetation density is a control on sediment transport at sub‐meter scales. Scour around single and dense clusters of pneumatophores was predicted by a standard hydraulic engineering equation for wave‐induced scour around regular cylinders, when the cylinder diameter in the equations was replaced with the representative diameter of the dense pneumatophore clusters. Waves were dissipated as they propagated into the forest, but dissipation at infragravity periods (> 30 s) was observed to be less than dissipation at shorter periods (< 30 s), consistent with the predictions of a simple model. Cross‐wavelet analysis revealed that infragravity‐frequency fluctuations in the bed level were occasionally coherent with velocity, possibly indicating scour upstream of dense pneumatophore patches when infragravity waves reinforced tidal currents. Consequently, infragravity waves were a likely driver of sediment transport within the mangrove forest. Near‐bed turbulent kinetic energy, estimated from the turbulent dissipation rate, was also correlated with bed level changes. Specifically, within the mangrove forest and over the unvegetated mudflat, high‐energy events were associated with erosion or near‐zero bed level change, whereas low‐energy events were associated with accretion. In contrast, no single relationship between bed level changes and mean current velocity was applicable across both vegetated and unvegetated regions. These observations support the theory that sediment mobilization scales with turbulent energy, rather than mean velocity, a distinction that becomes important when vegetation controls the development of turbulence. [ABSTRACT FROM AUTHOR]

Juries are the lifeblood of our criminal justice system. As the Framers clearly understood, and as the Supreme Court has consistently reaffirmed in recent years, their value goes far beyond accuracy in individual cases. Criminal juries are a democratic bulwark against overzealous state power; they keep prosecutors and police in check. Accordingly, the disappearance of traditional criminal trials is not just a problem for individual defendants. It is a problem for all of us. In this Article, we propose a novel mechanism to (partly) restore the criminal jury to its rightful pride of place--a trial lottery. In short, a small percentage of cases that plead out should be randomly selected for jury trial notwithstanding the plea, using the plea's terms as an upper limit on punishment. Such a system of lottery trials would yield three systemic benefits. First, it would counteract asymmetries in plea negotiations, leading to a more level field of bargaining. Second, it would 'audit' the law enforcement process, revealing patterns and irregularities in how police investigate and how prosecutors charge. Third, it would revitalize the role of jurors, lawyers, and judges in criminal adjudication. A trial lottery could thus restore a measure of accountability and democratic spirit to criminal justice systems that increasingly feel distressingly void of both. [ABSTRACT FROM AUTHOR]

The core proposition of the Fifth Amendment's Double Jeopardy Clause is as intuitive as it is straightforward. After all, if a state could prosecute someone despite her previous conviction or acquittal, then the scope of punishment would be unlimited and its threat unending--the sort of proposition only a tyrant could love. Yet, in Gamble v. United States, the Supreme Court once again blessed a dual sovereignty exception that permits just such duplicative prosecutions. We hardly are the first to question this rule, but we submit the Court's most recent primary mistakes were two. First, the Court began from a conception of constitutional community contrary to our Framers' own; and when one reaches for a grab bag of history, jurisprudence, and commentary, that starting point makes a difference. Second, the Court ignored both the logic of America's founding and recent double jeopardy jurisprudence, both of which strongly counsel against the exception in the federal-state context. We hope that a future Court will be more receptive to the nation's constitutional structure and to the genuine but limited needs of criminal justice. [ABSTRACT FROM AUTHOR]

Changes to the delivery of oral surgical services, the production and review of clinical guidelines, increased availability of cross-sectional imaging and the introduction of alternative techniques for surgical management of third molar disease have subtly changed the care that a patient will receive. In reviewing those changes, this article aims to promote continued discussion by the profession as to how patients can be best treated while avoiding a protectionist approach to patient care. [ABSTRACT FROM AUTHOR]

A dense population of embryo-derived Langerhans cells (eLCs) is maintained within the sealed epidermis without contribution from circulating cells. When this network is perturbed by transient exposure to ultraviolet light, short-term LCs are temporarily reconstituted from an initial wave of monocytes but thought to be superseded by more permanent repopulation with undefined LC precursors. However, the extent to which this process is relevant to immunopathological processes that damage LC population integrity is not known. Using a model of allogeneic hematopoietic stem cell transplantation, where alloreactive T cells directly target eLCs, we have asked whether and how the original LC network is ultimately restored. We find that donor monocytes, but not dendritic cells, are the precursors of long-term LCs in this context. Destruction of eLCs leads to recruitment of a wave of monocytes that engraft in the epidermis and undergo a sequential pathway of differentiation via transcriptionally distinct EpCAM+ precursors. Monocyte-derived LCs acquire the capacity of self-renewal, and proliferation in the epidermis matched that of steady-state eLCs. However, we identified a bottleneck in the differentiation and survival of epidermal monocytes, which, together with the slow rate of renewal of mature LCs, limits repair of the network. Furthermore, replenishment of the LC network leads to constitutive entry of cells into the epidermal compartment. Thus, immune injury triggers functional adaptation of mechanisms used to maintain tissue-resident macrophages at other sites, but this process is highly inefficient in the skin. [ABSTRACT FROM AUTHOR]

High‐resolution velocity measurements were collected within and above two dense canopies of mangrove pneumatophore roots in a wave‐exposed mangrove forest. In both canopies, root density decreased steadily with height above bed owing to the variability in root heights and the tapered shape of the roots. Within the canopies, we consider turbulence within three zones: near the bed above the wave boundary layer, around the mean canopy height, and above the canopy. The near‐bed turbulence was particularly intense (up to 6.5 × 10−4 W/kg), likely owing to oscillatory wave‐driven currents flowing past dense vegetation. Near the bed and around the mean canopy height, peaks in horizontal velocity power spectra at frequencies corresponding to Strouhal numbers of ~0.2 may indicate Von Kármán wake shedding in the lee of the pneumatophores. Furthermore, a recirculation zone was observed immediately behind a cluster of pneumatophores at intermediate heights. These coherent flow structures were associated with zones of enhanced Reynolds stresses (up to 5.3 × 10−3 m2/s2) and eddy viscosities (up to 1.9 × 10−3 m2/s). Large near‐bed stresses were associated with near‐bed drag coefficients that are up to an order of magnitude larger than those expected in the absence of vegetation. Observed eddy viscosities are consistent with theoretical expectations, derived from scaling arguments using a standard mixing‐length model. These results suggest that pneumatophore roots can contribute greatly to turbulent mixing (e.g., eddy viscosities were on average O(10−4–10−3 m2/s) and therefore may enhance the sediment transport occurring in mangrove forest fringes. Plain Language Summary: Mangrove forests comprise the dominant plant communities in tropical and subtropical coasts and provide many important physical and biological functions. However, mangrove forests are largely in decline worldwide, and hence, there is interest in rehabilitating or replanting damaged forests. The success rate of these efforts may be improved by understanding the physical forces that shape mangrove ecosystems. In this study, we deployed several high‐resolution velocity sensors within the pneumatophore roots of a coastal mangrove forest in the lower Mekong Delta, Vietnam. From velocity measurements, we assessed the spatial distribution of turbulence that formed in the wake of the roots when they were submerged during the rising or falling tide. We found that enhanced turbulence was associated with denser vegetation, particularly near the bed. This result indicates that pneumatophore roots do not necessarily shelter the bed from erosional forces and instead may enhance sediment transport occurring within the forest. Key Points: Turbulent dissipation, Reynolds stress, and eddy viscosity are enhanced near the bed within clusters of mangrove pneumatophore rootsEddy viscosities up to 1.9 x 10‐3 m2/s were estimated within the vegetationPneumatophore roots may inhibit sediment deposition, which contradicts the expectation that dense vegetation promotes sediment retention [ABSTRACT FROM AUTHOR]

This article draws from interviews with music promoters from the northern England to consider their use of social media to develop online communities. It reveals they have developed online spaces offering digital leisure for the making and enjoying of music, but the forming of these music-loving communities is problematic. Promoters are necessarily distracted by what might be called a corporate community of agents, local councils, and so forth. Promoting itself is complicated by the social community of live music fans with its different music genre-based subcommunities. As a result, complex community structures form around “pools,” “webs,” and “hubs” with whom the promoters communicate in both instrumental and communicative ways. Underpinning this social construct, activity in the community is predominantly transactional and instrumental in an approach that differs little from the equivalent offline world and, as a result, offers little as a transformative space for social justice. [ABSTRACT FROM AUTHOR]

As with most new things, the big data revolution in criminal justice has historic antecedents--indeed, a 1965 Presidential Commission called for some of the same data analysis that police departments and courts are today developing and implementing. But there is no doubt we are on the precipice of a criminal justice data revolution, and it is a good time to take stock and to begin developing guidelines so that, as much as possible, criminal justice systems might reap the benefits and avoid the pitfalls of this newly data-centric world. In that spirit, I propose ten high-level rules to guide criminal justice big data implementations. [ABSTRACT FROM AUTHOR]

We finally have a federal 'test case.' In Carpenter v. United States, the Supreme Court is poised to set the direction of the Fourth Amendment in the digital age. The case squarely presents how the twentieth-century third party doctrine will fare in contemporary times, and the stakes could not be higher. This Article reviews the Carpenter case and how it fits within the greater discussion of the Fourth Amendment third party doctrine and location surveillance, and I express a hope that the Court will be both a bit ambitious and a good measure cautious. As for ambition, the Court must recognize that the fundamental liberty protected by the Fourth Amendment--the right to be "secure in [our] persons, houses, papers, and effects"--is squarely at issue when the government seeks to track our longer term movements, whether historically or prospectively. It is not business records, beepers, automobiles, phones, cameras, drones, or some other coincidental medium or technology that is at issue: it is our constitutionally protected liberty. Thus, the Court should hold that law enforcement acquisition of longer term cell site location information (CSLI) constitutes a Fourth Amendment search, ending the monolithic, anachronistic third party doctrine. As to the precise durational trigger and as to what particular law enforcement restraint would be correspondingly reasonable, the Court should be cautious, as it was in United States v. Jones and Grady v. North Carolina. It will have taken the better part of a half century to undo the Court's expansive third-party declaration in United States v. Miller, an unnecessary overreach best relegated to history. Thus, while the Court should not abandon Fourth Amendment development through reasonable reliance, it should remand these constitutional determinations for lower court development. Those courts should consider not only Fourth Amendment precedents, but also how state supreme courts have independently interpreted their own constitutions. [ABSTRACT FROM AUTHOR]

The three-dimensional (across-shore, alongshore, and vertical) structure of hourly mean currents and <0.01 Hz eddies was measured on a natural beach using 12 Acoustic Doppler Profilers. Both eddies and alongshore currents became relatively depth-uniform inside the surfzone. Eddies showed greater depth dependence than alongshore currents. A two-layer model, derived by scaling of the wave-averaged shallow water equations, yielded separate equations for depth-averaged and depth-dependent velocity components. Scaling suggests, and observations confirm, only a small role for lateral advection in most surfzone cases, leading to one-dimensional vertical models for depth dependence. For alongshore currents, depth dependence is generated by opposite forcing on lower and upper layers, respectively by bottom friction (quantified by time scale [ABSTRACT FROM AUTHOR]

Mangrove forests are highly productive ecosystems that provide many physical, societal, and ecological services in tropical and subtropical regions. Accurate prediction of the morphological evolution for these areas, in the face of global sea level rise and changes in sediment supply, requires understanding of interactions between vegetation growth, water flows, and sediment transport. Data presented from a waveexposed mangrove forest in the Mekong Delta, Vietnam, include unique measurements that resolved water flows in and around the aerial mangrove roots (known as pneumatophores) over scales from a few millimeters to hundreds of meters. Flows were highly turbulent, with turbulence values sometimes as large as those measured in surf zones. These energetic processes appear to stir up sediments, with small scour troughs observed around individual pneumatophores, and larger-scale scour around clusters of pneumatophores. The vegetation fringe (the boundary between forest and mudflat) was a particularly dynamic area, with elevated turbulence levels, greater vegetation densities, coarser sediments, and occasional wave breaking. Intense turbulent dissipation at the fringe then reduces the energy of shoreward-propagating waves, sheltering the forest interior. The small-scale processes appear to be linked with forest-wide patterns of sediment transport and deposition. We discuss these links in the context of the biophysical interactions that control the changing shapes of deltas worldwide. [ABSTRACT FROM AUTHOR]

Metabolic changes within the cell and its niche affect cell fate and are involved in many diseases and disorders including cancer and viral infections. Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi’s sarcoma (KS). KSHV latently infected cells express only a subset of viral genes, mainly located within the latency-associated region, among them 12 microRNAs. Notably, these miRNAs are responsible for inducing the Warburg effect in infected cells. Here we identify a novel mechanism enabling KSHV to manipulate the metabolic nature of the tumour microenvironment. We demonstrate that KSHV infected cells specifically transfer the virus-encoded microRNAs to surrounding cells via exosomes. This flow of genetic information results in a metabolic shift toward aerobic glycolysis in the surrounding non-infected cells. Importantly, this exosome-mediated metabolic reprogramming of neighbouring cells supports the growth of infected cells, thereby contributing to viral fitness. Finally, our data show that this miRNA transfer-based regulation of cell metabolism is a general mechanism used by other herpesviruses, such as EBV, as well as for the transfer of non-viral onco-miRs. This exosome-based crosstalk provides viruses with a mechanism for non-infectious transfer of genetic material without production of new viral particles, which might expose them to the immune system. We suggest that viruses and cancer cells use this mechanism to shape a specific metabolic niche that will contribute to their fitness. [ABSTRACT FROM AUTHOR]

The English Premier League remains the envy of the rest of the world with eight clubs from this league in the top twenty based on revenue (Deloitte & Touche, 2007). This paper sets out to examine the impact of technology on those clubs. Secondary research identifies that a globalisation trend amongst the larger clubs is driving a variety of revenue streams. How technology is helping the clubs to create a wide range of service offerings for football fans in the UK and beyond is highlighted. It becomes clear that broadcasting is key in its ability to not only generate revenue in its own right but also increase merchandise and sponsorship revenues. The differing types of football fan are considered but it is discovered that the available research concentrates on fans attending matches. The global fan is expected to show a different pattern of consumption in terms of the location of consumption as well as the service itself. It becomes clear that not only is little known about the fans who don't regularly attend matches but that there is some scepticism about whether the technology will meet their needs. Alongside the secondary research noted above, primary research takes a look at 3G mobile phone technology as a way to examine the views on technology of the top-flight football clubs in the English Premier League. Clear, wide ranging, technically based strategies are observed amongst the larger football clubs enabling them to reach out to their global fan base. The findings support the view that there is a widening gap between the 'haves' and 'have nots'. Furthermore, they confirm the view that, whilst broadcasting rights are increasing their revenues, there remain gaps in market knowledge and mistrust of technologies that are neither necessarily stable nor offer the market a product that is valued. [ABSTRACT FROM AUTHOR]

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The polarization of CD4+ T cells into distinct T helper cell lineages is essential for protective immunity against infection, but aberrant T cell polarization can cause autoimmunity. The transcription factor T-bet (TBX21) specifies the Th1 lineage and represses alternative T cell fates. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) that may be causative for autoimmune diseases. The majority of these polymorphisms are located within non-coding distal regulatory elements. It is considered that these genetic variants contribute to disease by altering the binding of regulatory proteins and thus gene expression, but whether these variants alter the binding of lineage-specifying transcription factors has not been determined. Here, we show that SNPs associated with the mucosal inflammatory diseases Crohn’s disease, ulcerative colitis (UC) and celiac disease, but not rheumatoid arthritis or psoriasis, are enriched at T-bet binding sites. Furthermore, we identify disease-associated variants that alter T-bet binding in vitro and in vivo. ChIP-seq for T-bet in individuals heterozygous for the celiac disease-associated SNPs rs1465321 and rs2058622 and the IBD-associated SNPs rs1551398 and rs1551399, reveals decreased binding to the minor disease-associated alleles. Furthermore, we show that rs1465321 is an expression quantitative trait locus (eQTL) for the neighboring gene IL18RAP, with decreased T-bet binding associated with decreased expression of this gene. These results suggest that genetic polymorphisms may predispose individuals to mucosal autoimmune disease through alterations in T-bet binding. Other disease-associated variants may similarly act by modulating the binding of lineage-specifying transcription factors in a tissue-selective and disease-specific manner. [ABSTRACT FROM AUTHOR]

The General Dental Council has been through a very difficult period, and there is an appetite within government and the profession for a review of healthcare regulation, with an emphasis on right-touch regulation. The background to those difficulties is reviewed and the nature and impact of changes to the Dentist Act, which are being introduced during 2016, is discussed. The role of the Professional Standards Authority in regulating the healthcare professional is also explained. [ABSTRACT FROM AUTHOR]

The F-Club in Leeds, UK, was a punk and post-punk night club from the 1970s to the 1980s. Leeds as a city has a reputation for alternative music scenes, and the F-Club is part of the history recalled by musicians and fans locally. In this article, we interview people who publicly identified with going to the F-Club back in their youth, to map connections as well as memories, identity-work and myth-making. We are interested in leisure spaces and leisure lives, as well as cultural spaces and identity-work. We explore the history of the F-Club, its place in wider networks, and the memories of it by those who attended it. We explore the ways in which the F-Club is remembered and talked about by self-declared members of the scenes around the club. Our interest is not so much in mapping and understanding the identity-work and the community of the F-Club as it actually happened, but in how our respondents construct these things now from their own memories. This article also contributes to methodological and theoretical debates about network analysis against ethnography in the sociology of music, and defends the latter as a way to construct an emerging public sociology of leisure. [ABSTRACT FROM AUTHOR]

In a small lake, where flows were dominated by internal waves with 10-32-h period, slow but persistent mean transport of water over many wave periods was examined. Acoustic Doppler profilers (ADPs) and a vertical string of temperature loggers were deployed where the lower thermocline intersected the sloping lakebed. Near (<1 m above) the bed, internal waves, coherent with a lakewide seiche, propagated upslope at ~0.023 m s−1. Near-bed wave-induced water velocity fluctuations had a standard deviation of <0.02 m s−1. Near the surface, velocity fluctuations had similar magnitude, but lateral wave propagation was unclear. Averaged over many wave periods, the near-bed Eulerian velocity flowed downslope at ~0.01 m s−1, and was roughly cancelled by an upslope internal-wave Stokes drift (estimated by assuming that weakly nonlinear waves propagated without change of form). To examine net transport, while relaxing approximations used to estimate the Stokes drift, the observed temperature range (9°-25°C) was divided into 0.5°C increments, and the depth-integrated, wave-averaged flux of water in each temperature class was calculated. The coldest (near-bed) water was slowly transported onshore, opposite the Eulerian mean velocity. Onshore flux of warm near-surface water was comparable to an Eulerian-mean flux, indicating minimal near-surface Stokes drift. Intermediate water, from the middle of the water column and the outer boundary layer, was transported offshore by an offshore Stokes drift. The downslope near-bed Eulerian mean velocity, together with intensification of mean stratification within 0.4 m of the bed, may enhance boundary layer mixing. [ABSTRACT FROM AUTHOR]

When it comes to criminal investigation, time travel is increasingly possible. Despite longstanding roots in traditional investigation, science is today providing something fundamentally different in the form of remarkably complete digital records. And those big data records not only store our past, but thanks to data mining they are in many circumstances eerily good at predicting our future. So, now that we stand on the threshold of investigatory time travel, how should the Fourth Amendment and legislation respond? How should we approach bulk government capture, such as by a solar-powered drone employing wide-area persistent stare technology? Is it meaningfully different from civilian equivalents that find their way into government hands, whether it be tomorrow's drone flight, or today's record of all of our internet activity compiled by our internet service provider, or a current record of all of our movements compiled by our mobile phone company? What of targeted time machines such as government over-seizure of digital data in every computer search? This Article considers the benefits and costs of these miraculous timemachine technologies, including as evidenced by several recent court opinions. Considering the very serious privacy implications--from the individual to the relational and societal--we have good reason to be wary of their coming ubiquity. Yet perhaps in very limited spheres we should welcome them, going so far as to entirely abandon front-end acquisition restrictions and rely solely upon ex post access, use, and disclosure limitations to protect the security in our persons, houses, papers, and effects. I suggest that one such sphere might be law enforcement body cameras, an instance in which full capture has great benefits, and via which we can experiment upon the utility of solely ex post restraints. [ABSTRACT FROM AUTHOR]

The article launches a constitutionally grounded, but lighthearted campaign of citizen education and empowerment: Fourth Amendment lawn signs in the U.S. It says that ordinary citizens, with every stake in the ground, can proclaim their expectations and tell everyone that the Fourth Amendment is meant to apply to common people in everyday circumstances.

Dendritic cells (DCs) play a vital role in innate and adaptive immunities. Inducible depletion of CD11c+ DCs engineered to express a high-affinity diphtheria toxin receptor has been a powerful tool to dissect DC function in vivo. However, despite reports showing that loss of DCs induces transient monocytosis, the monocyte population that emerges and the potential impact of monocytes on studies of DC function have not been investigated. We found that depletion of CD11c+ cells from CD11c.DTR mice induced the expansion of a variant CD64+ Ly6C+ monocyte population in the spleen and blood that was distinct from conventional monocytes. Expansion of CD64+ Ly6C+ monocytes was independent of mobilization from the BM via CCR2 but required the cytokine, G-CSF. Indeed, this population was also expanded upon exposure to exogenous G-CSF in the absence of DC depletion. CD64+ Ly6C+ monocytes were characterized by upregulation of innate signaling apparatus despite the absence of inflammation, and an increased capacity to produce TNF-α following LPS stimulation. Thus, depletion of CD11c+ cells induces expansion of a unique CD64+ Ly6C+ monocyte population poised to synthesize TNF-α. This finding will require consideration in experiments using depletion strategies to test the role of CD11c+ DCs in immunity. [ABSTRACT FROM AUTHOR]

The FAA Modernization and Reform Act of 2012 requires the Federal Aviation Administration to integrate unmanned aerial vehicles (UAVs), or drones, into the national airspace system by September 2015. Yet perhaps because of their chilling accuracy in targeted killings abroad, perhaps because of an increasing consciousness of diminishing privacy more generally, and perhaps simply because of a fear of the unknown, divergent UAV-restrictive legislation has been proposed in Congress and enacted in a number of states. Given UAV utility and cost-effectiveness over a vast range of tasks, however, widespread commercial use ultimately seems certain. Consequently, it is imperative to understand the constitutional restraints on public flight and constitutional protections afforded to private flight. Unfortunately, although there are a few Fourth Amendment precedents in manned aviation, they are mired not only in 1980s technology but also in the 1980s third party doctrine, and therefore do not reflect more recent Fourth Amendment developments and doctrinal fissures. There is also considerable uncertainty over First Amendment protection of information-gathering--for example, is there a right to record? Further, there is no judicial or scholarly analysis of how UAV flight fits within contemporary First Amendment forum doctrine, a framework that provides a useful starting point for analyzing speech restrictions in government-controlled airspace, but that comes with some uncertainties of its own. It is into this thicket that we dive, and fortunately some clarity emerges. Although the Fourth Amendment third party doctrine hopelessly misunderstands privacy and therefore under-protects our security and liberty interests, the Supreme Court's manned flyover cases can be mined for a sensible public disclosure doctrine that seems agnostic as to the various Fourth Amendment conceptions: we do not typically require only law enforcement to shield its eyes. Of course, both constitutions and legislation can place special restrictions upon law enforcement, and sometimes doing so makes good sense. But as a general Fourth Amendment matter, the officer may do and see as the citizen would. Hence to understand Fourth Amendment regulation, we must understand how the First Amendment limits government restraint on speech-relevant private UAV flight. Here we analyze the developing right to record and apply contemporary forum doctrine to this novel means of speech and information-gathering. If navigable airspace is treated as a limited public forum, as we propose with some qualification, then the Federal Aviation Administration will have significant--though not unlimited--regulatory leeway to evenhandedly burden speech-related UAV activities where doing so would reasonably promote safe unmanned and manned flight operations. The Agency, however, would likely need further congressional action before it can restrict UAV flight based on privacy rather than safety concerns. As the legality and norms of private flight correspondingly take shape, they will inform Fourth Amendment restrictions on government use. [ABSTRACT FROM AUTHOR]

In lakes and reservoirs, the bottom boundary layer (BBL) mediates chemical fluxes between sediments and the overlying water column. At the internal shoreline, where the thermocline contacts the lakebed, the motions of internal waves can create fluctuating redox conditions and dynamic physical forcing that may support ecologically important reactions such as denitrification. We characterized physical and chemical dynamics within the internal shoreline of a eutrophic reservoir during the spring and early summer of 2012 (18 May to 18 July). An internal seiche was found to generate quasi-periodic fluctuations (periods about 12-24 h) in BBL stratification, temperature, and redox conditions. To examine possible implications for chemical mixing and microbial processing, differences between vertically offset, simultaneous BBL measurements of velocity, temperature, N2, and N2O were made over 23 h. Vertical differences in BBL temperature, N2, and N2O formed and collapsed during the wave cycle, with the largest differences occurring following the arrival of an internal bore. Through much of the wave cycle, chemical differences were explained by physical advection and mixing. However, chemical differences measured after bore arrival were not explained by advection, possibly owing to local production of N2 and N2O. These results highlight the dynamic physical environment within the internal shoreline, and the potential of this zone to contribute to system wide denitrification and nitrous oxide production. [ABSTRACT FROM AUTHOR]

The article focuses on granulocyte colony-stimulating factor (G-CSF) which is routinely used to collect peripheral blood stem cells (PBSCs) from healthy donors for allogeneic hematopoietic stem cell transplantation (allo-HSCT). It mentions G-CSF mobilizes a subset of CD34 cells with mature monocyte features and endowed with immunosuppressive properties. It also mentions Interferon gamma released by activated T cells and cells produce nitric oxide which induces allogeneic T cell death.

Summary Topological domains are key architectural building blocks of chromosomes, but their functional importance and evolutionary dynamics are not well defined. We performed comparative high-throughput chromosome conformation capture (Hi-C) in four mammals and characterized the conservation and divergence of chromosomal contact insulation and the resulting domain architectures within distantly related genomes. We show that the modular organization of chromosomes is robustly conserved in syntenic regions and that this is compatible with conservation of the binding landscape of the insulator protein CTCF. Specifically, conserved CTCF sites are co-localized with cohesin, are enriched at strong topological domain borders, and bind to DNA motifs with orientations that define the directionality of CTCF’s long-range interactions. Conversely, divergent CTCF binding between species is correlated with divergence of internal domain structure, likely driven by local CTCF binding sequence changes, demonstrating how genome evolution can be linked to a continuous flux of local conformation changes. We also show that large-scale domains are reorganized during genome evolution as intact modules. [ABSTRACT FROM AUTHOR]

In late 2014, two grand, juries returned controversial no bill decisions in police killings, one in Ferguson, Missouri, and one in New York City. These outcomes have renewed calls for grand jury reform, and whatever one thinks of these particular processes and outcomes, such reform is long overdue. One logical source of reform to better respect privacy in records, which would have incidental benefits beyond this privacy focus, would be the newly enacted American Bar Association Standards for Criminal Justice on Law Enforcement Access to Third Party Records (LEATPR). But LEATPR exempts from its requirements access to records via a grand jury subpoena, and, perhaps more surprisingly, potentially exempts access via a "functionally equivalent prosecutorial subpoena." The impetus for this exemption was a concern that applying LEATPR's requirements to the grand jury, or even to its functional equivalent, is unnecessary and might radically undermine longstanding systems of criminal investigation in perhaps unforeseeable ways. This Article addresses whether this exception can be justified by reviewing each of the four main regulatory mechanisms of LEATPR and examining whether grand jury procedures provide an adequate substitute. In finding that they do not, this Article indicates how to improve the grand jury process. These improvements would of course not resolve the very difficult and multifaceted social ills reflected in the controversy over recent grand jury decisions, but they could begin to restore the legitimacy of this once-revered but now-maligned institution. [ABSTRACT FROM AUTHOR]

T cell pathology in the skin leads to monocyte influx, but we have little understanding of the fate of recruited cells within the diseased niche, or the long-term impact on cutaneous immune homeostasis. By combining a murine model of acute graft-versus-host disease (aGVHD) with analysis of patient samples, we demonstrate that pathology initiates dermis-specific macrophage differentiation and show that aGVHD-primed macrophages continue to dominate the dermal compartment at the relative expense of quiescent MHCIIint cells. Exposure of the altered dermal niche to topical haptens after disease resolution results in hyper-activation of regulatory T cells (Treg), but local breakdown in tolerance. Disease-imprinted macrophages express increased IL-1β and are predicted to elicit altered TNF superfamily interactions with cutaneous Treg, and we demonstrate the direct loss of T cell regulation within the resolved skin. Thus, T cell pathology leaves an immunological scar in the skin marked by failure to re-set immune homeostasis. [Display omitted] • Skin immune pathology drives dermis-specific monocyte differentiation • GVHD-primed macrophages dominate the dermis after disease • T cell tolerance to topical haptens fails despite recovery from GVHD • Tregs are dysfunctional within the altered dermal niche The impact of T cell pathology on cutaneous immunity is not well understood. Here, West et al. combine a model of graft-versus-host-disease with patient data to reveal prolonged dysregulation of dermal macrophage differentiation, and breakdown in Treg function, leading to a failure to re-set the skin immune balance after disease. [ABSTRACT FROM AUTHOR]

Purpose -- To translate theory into a practical tool, the purpose of this paper is to provide a conceptual framework for the development of social marketing strategies to modify event attendee behaviour in a sustainable direction. Design/methodology/approach -- Consumer value is synthesised with social marketing and consumer behaviour theory to develop the framework. A major problem for festivals (throwaway tents) and current pro-environmental practices are used to determine the framework's applicability. Findings -- The conceptual framework suggests that achieving desired behaviour(s) within an audience requires consideration of the added value at the downstream level, strategies that recognise offsite/onsite behaviour settings, engagement of upstream advocacy and more attention to the evaluation of success. Research limitations/implications -- A single low-involvement behaviour example is used to validate the conceptual framework suggesting further work is needed to widen tests of its applicability. Originality/value -- This paper synthesises theory into a framework that has significant potential as a tool to develop behavioural change strategies at events. [ABSTRACT FROM AUTHOR]

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Summary: APOBEC3B cytosine deaminase activity has recently emerged as a significant mutagenic factor in human cancer. APOBEC activity is induced in virally infected cells, and APOBEC signature mutations occur at high frequency in cervical cancers (CESC), over 99% of which are caused by human papillomavirus (HPV). We tested whether APOBEC-mediated mutagenesis is particularly important in HPV-associated tumors by comparing the exomes of HPV+ and HPV− head and neck squamous cell carcinomas (HNSCCs) sequenced by The Cancer Genome Atlas project. As expected, HPV− HNSCC displays a smoking-associated mutational signature, whereas our data suggest that reduced exposure to exogenous carcinogens in HPV+ HNSCC creates a selective pressure that favors emergence of tumors with APOBEC-mediated driver mutations. Finally, we provide evidence that APOBEC activity is responsible for the generation of helical domain hot spot mutations in the PIK3CA gene across multiple cancers. Our findings implicate APOBEC activity as a key driver of PIK3CA mutagenesis and HPV-induced transformation. [Copyright &y& Elsevier]

Background The transcription factor Nrf2 is a key regulator of the cellular antioxidant response, and its activation by chemoprotective agents has been proposed as a potential strategy to prevent cancer. However, activating mutations in the Nrf2 pathway have been found to promote tumorigenesis in certain models. Therefore, the role of Nrf2 in cancer remains contentious. Methods We employed a well-characterized model of stepwise human mesenchymal stem cell (MSC) transformation and breast cancer cell lines to investigate oxidative stress and the role of Nrf2 during tumorigenesis. The Nrf2 pathway was studied by microarray analyses, qRT-PCR, and western-blotting. To assess the contribution of Nrf2 to transformation, we established tumor xenografts with transformed MSC expressing Nrf2 (n = 6 mice per group). Expression and survival data for Nrf2 in different cancers were obtained from GEO and TCGA databases. All statistical tests were two-sided. Results We found an accumulation of reactive oxygen species during MSC transformation that correlated with the transcriptional down-regulation of antioxidants and Nrf2-downstream genes. Nrf2 was repressed in transformed MSC and in breast cancer cells via oncogene-induced activation of the RAS/RAF/ERK pathway. Furthermore, restoration of Nrf2 function in transformed cells decreased reactive oxygen species and impaired in vivo tumor growth (P = 0.001) by mechanisms that included sensitization to apoptosis, and a decreased hypoxic/angiogenic response through HIF-1α destabilization and VEGFA repression. Microarray analyses showed down-regulation of Nrf2 in a panel of human tumors and, strikingly, low Nrf2 expression correlated with poorer survival in patients with melanoma (P = 0.0341), kidney (P = 0.0203) and prostate (P = 0.00279) cancers. Conclusions Our data indicate that oncogene-induced Nrf2 repression is an adaptive response for certain cancers to acquire a pro-oxidant state that favors cell survival and in vivo tumor growth. [ABSTRACT FROM AUTHOR]