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This Article proposes a new means of restraining police power: quantitative limits on the number of law enforcement intrusions—searches and seizures—that may occur over a given period of time. Like monetary constraints, search and seizure budgets would aim to curb abusive policing and improve democratic oversight. But unlike their monetary counterparts, budgets would be indexed directly to the specific police activities that most enable escalation and abuse. What is more, budgets are a tool that finds support, conceptually, in the American framing experience. The Fourth Amendment has long been understood to require procedural limits, such as probable cause, on specific police intrusions. But such requirements are only part of the story; limits on overall police capacity, we argue, are also hardwired into the Fourth Amendment via its founding era history. Search and seizure budgets would help reinvigorate that promise, offering an important tool in the ongoing effort to curb over-criminalization and the ever-expanding technologies of surveillance.

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.

Ponds are characterized by high biodiversity, intense biogeochemical cycling, and susceptibility to anthropogenic impacts. Yet few studies have quantified the water velocities responsible for vertical mixing or lateral transport in ponds. We used high‐resolution observations of velocity to examine mixing and transport during summer in a 50‐m‐long, 2.7‐m‐deep temperate pond. Many observed transport and mixing processes resembled those found in larger stratified lakes. A surface mixed layer was observed, whose depth ranged between ~ 1 m at night and < 0.3 m during the day. Turbulence was usually sufficient to vertically mix the surface layer in 4–12 min, but no turbulence was observed in the hypolimnion. Persistent (2.5‐h‐averaged) currents usually flowed downwind near the surface and returned upwind near the mixed layer base. Surface currents were proportional to windspeed, with root‐mean‐squared speed of 8×10−3ms−1$$ 8\times {10}^{-3}\ \mathrm{m}\;{\mathrm{s}}^{-1} $$ (persistent hypolimnion currents were much weaker). Superposed on persistent currents were 30‐ to 100‐min‐period fluctuations resulting from internal seiches. These fluctuations were comparable in magnitude to more persistent currents in the mixed layer and dominated in the hypolimnion. Seiches did not advect particles far across the pond, but did contribute to production of mixed layer turbulence. Seiches also contributed to shear dispersion, which was sufficient to mix near‐surface tracers across the pond in 2–4 d. Theory suggests that hypolimnion bottom boundary layers were laminar during the downslope phase of seiche motion, but became turbulent during the upslope phase as near‐bed water flows created unstable stratification. [ABSTRACT FROM AUTHOR]

Thus, it seems problematic to insist, as some lower courts have, that photography conducted for 'recreational and aesthetic' purposes lacks the First Amendment protection that would almost certainly prevent government [...]

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]

A conference of 47 science, mathematics, and technology educators and rural education experts from across the country prepared a research agenda regarding science and mathematics achievement in poor, rural schools. Researchable questions were grouped into categories of community support, instructional resources, leadership and school reform, professional development, preservice education and induction, curriculum and instruction, and databases. (Contains 21 references.) (TD)

Allogeneic blood or BM transplantation (BMT) is the most commonly applied form of adoptive cellular therapy for cancer. In this context, the ability of donor T cells to respond to recipient antigens is coopted to generate graft-versus-tumor (GVT) responses. The major reason for treatment failure is tumor recurrence, which is linked to the eventual loss of functional, host-specific CTLs. In this study, we have explored the role of recipient antigen expression by nonhematopoietic cells in the failure to sustain effective CTL immunity. Using clinically relevant models, we found that nonhematopoietic antigen severely disrupts the formation of donor [CD8.sup.+] T cell memory at 2 distinct levels that operate in the early and late phases of the response. First, initial and direct encounters between donor [CD8.sup.+] T cells and nonhematopoietic cells blocked the programming of memory precursors essential for establishing recall immunity. Second, surviving [CD8.sup.+] T cells became functionally exhausted with heightened expression of the coinhibitory receptor programmed death-1 (PD-1). These 2 factors acted together to induce even more profound failure in long-term immunosurveillance. Crucially, the functions of exhausted [CD8.sup.+] T cells could be partially restored by late in vivo blockade of the interaction between PD-1 and its ligand, PD-L1, without induction of graft-versus-host disease, suggestive of a potential clinical strategy to prevent or treat relapse following allogeneic BMT., Introduction Allogeneic blood or BM transplantation (BMT) represents the most commonly applied form of adoptive cellular therapy for cancer. This treatment exploits donor T cell alloreactivity to generate a graft-versus-tumor [...]

A genome-wide DNA-methylation profiling on familial breast cancer is performed to identify patterns of methylation which are particular to the different mutation groups or intrinsic types of breast cancer. Data obtained using a support vector machine classification algorithm, gene-expression profiling and SNP CGH array identify distinct methylation profiles defined by the mutation status, which are different from the intrinsic subtypes.