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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]

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]

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 [...]

Multiple studies explore the issue of the absence of teachers of color in the profession at large. Few studies, however, address the issue from the angle of the teacher candidate of color. With so many competing professions, why do they ultimately make the decision to join the profession? What are the contexts that influence and support that choice? What are the challenges that make that choice questionable? Here, the authors examine from these and other angles African American teacher candidates' decisions to teach.

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)

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]

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.

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]

While the American civic religion is to be distrustful of government, feelings of discontent regarding our systems of criminal investigation and adjudication feel historic. And while those systems are capable of great carnage en route, the endgame is, ultimately, criminal punishment. Yet before punishment can be imposed, every prosecution--and therefore every defendant--is meant to encounter a potential "circuit breaker": the jury. I propose that we re-inject this democratic voice into our criminal adjudications, but through an entirely novel structure: the defendant (and perhaps the prosecutor) would have the choice of invoking a jury empowered to 'veto' any judicial sentence. By carefully designing the ex post system, including to discourage over-invocation, we could provide more democratic results in individual cases, hold prosecutors to their charging threats, and obtain a meaningful sense of whether--as many of us believe--our institutions of criminal justice are dangerously out of touch with popular conceptions of what ought to be. [ABSTRACT FROM AUTHOR]

Mg(super.2+)-dependent compaction and folding of yeast tRNA(super.Phe) and the catalytic domain of the Bacillus subtilis RNase P RNA have been studied using synchrotron-based small-angle X-ray scattering. It was found that there is strong support for the cooperative Mg(super.2+)-binding model to account for the stability of a tertiary RNA.

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]