High Resolution Observations of GRB 030329

The nearby (z=0.1685) gamma-ray burst of 29 March 2003 has presented us with a unique opportunity to study an event with unprecedented physical resolution. This burst reached flux density levels at centimeter wavelengths more than 50 times brighter than any previously studied event. Here we present the results of VLBI observations that have resolved the radio afterglow, and constrain its proper motion in the sky to <0.3 mas. The size of the afterglow is measured to be ~0.08 mas 24 days after the burst, consistent with expectations of the standard fireball model. In observations taken 51 days after the burst we detect an additional compact, "jet", component at a distance from the main component of 0.28 ± 0.05 mas. The presence of this jet component is not consistent with the standard model

United States Reexamination Procedures: Recent Trends, Strategies and Impact on Patent Practice, 8 J. Marshall Rev. Intell. Prop. L. 381 (2009)

Reexamination is playing a significant role in the patent landscape. The United States Patent and Trademark Office is reexamining and invalidating more patent claims than ever before. Potential infringers, aware of this trend, can benefit from reexamination proceedings initiated before, during, and after litigation. Moreover, a prevalent reexamination system benefits both the public and industry. Efficient reexamination enables parties to challenge overly broad patents at a reasonable cost which reduces transaction costs, promoting innovation. Patent holders have responded by crafting narrow claims which fair well before the patent office and in court. The current reexamination trend, if continued, will have a strong and positive effect on innovation in the United States

Toward a statistical mechanics of four letter words

We consider words as a network of interacting letters, and approximate the probability distribution of states taken on by this network. Despite the intuition that the rules of English spelling are highly combinatorial (and arbitrary), we find that maximum entropy models consistent with pairwise correlations among letters provide a surprisingly good approximation to the full statistics of four letter words, capturing ~92% of the multi-information among letters and even "discovering" real words that were not represented in the data from which the pairwise correlations were estimated. The maximum entropy model defines an energy landscape on the space of possible words, and local minima in this landscape account for nearly two-thirds of words used in written English

Prefrontal cortical microcircuits bind perception to executive control

During the perception-to-action cycle, our cerebral cortex mediates the interactions between the environment and the perceptual-executive systems of the brain. At the top of the executive hierarchy, prefrontal cortical microcircuits are assumed to bind perceptual and executive control information to guide goal-driven behavior. Here, we tested this hypothesis by comparing simultaneously recorded neuron firing in prefrontal cortical layers and the caudate-putamen of rhesus monkeys, trained in a spatial-versus-object, rule-based match-to-sample task. We found that during the perception and executive selection phases, cell firing in the localized prefrontal layers and caudate-putamen region exhibited similar location preferences on spatial-trials, but less on object- trials. Then, we facilitated the perceptual-executive circuit by stimulating the prefrontal infra-granular-layers with patterns previously derived from supra-granular-layers, and produced stimulation-induced spatial preference in percent correct performance on spatial trials, similar to neural tuning. These results show that inter-laminar prefrontal microcircuits play causal roles to the perception-to-action cycle

Distributed Encoding of Spatial and Object Categories in Primate Hippocampal Microcircuits

The primate hippocampus plays critical roles in the encoding, representation, categorization and retrieval of cognitive information. Such cognitive abilities may use the transformational input-output properties of hippocampal laminar microcircuitry to generate spatial representations and to categorize features of objects, images, and their numeric characteristics. Four nonhuman primates were trained in a delayed-match-to-sample (DMS) task while multi-neuron activity was simultaneously recorded from the CA1 and CA3 hippocampal cell fields. The results show differential encoding of spatial location and categorization of images presented as relevant stimuli in the task. Individual hippocampal cells encoded visual stimuli only on specific types of trials in which retention of either, the Sample image, or the spatial position of the Sample image indicated at the beginning of the trial, was required. Consistent with such encoding, it was shown that patterned microstimulation applied during Sample image presentation facilitated selection of either Sample image spatial locations or types of images, during the Match phase of the task. These findings support the existence of specific codes for spatial and numeric object representations in primate hippocampus which can be applied on differentially signaled trials. Moreover, the transformational properties of hippocampal microcircuitry, together with the patterned microstimulation are supporting the practical importance of this approach for cognitive enhancement and rehabilitation, needed for memory neuroprosthetics

Aerothermodynamic Analyses of Towed Ballutes

A ballute (balloon-parachute) is an inflatable, aerodynamic drag device for application to planetary entry vehicles. Two challenging aspects of aerothermal simulation of towed ballutes are considered. The first challenge, simulation of a complete system including inflatable tethers and a trailing toroidal ballute, is addressed using the unstructured-grid, Navier-Stokes solver FUN3D. Auxiliary simulations of a semi-infinite cylinder using the rarefied flow, Direct Simulation Monte Carlo solver, DSV2, provide additional insight into limiting behavior of the aerothermal environment around tethers directly exposed to the free stream. Simulations reveal pressures higher than stagnation and corresponding large heating rates on the tether as it emerges from the spacecraft base flow and passes through the spacecraft bow shock. The footprint of the tether shock on the toroidal ballute is also subject to heating amplification. Design options to accommodate or reduce these environments are discussed. The second challenge addresses time-accurate simulation to detect the onset of unsteady flow interactions as a function of geometry and Reynolds number. Video of unsteady interactions measured in the Langley Aerothermodynamic Laboratory 20-Inch Mach 6 Air Tunnel and CFD simulations using the structured grid, Navier-Stokes solver LAURA are compared for flow over a rigid spacecraft-sting-toroid system. The experimental data provides qualitative information on the amplitude and onset of unsteady motion which is captured in the numerical simulations. The presence of severe unsteady fluid - structure interactions is undesirable and numerical simulation must be able to predict the onset of such motion

VLBI and Archival VLA and WSRT Observations of the GRB 030329 Radio Afterglow

We present VLBI and archival Karl G. Jansky Very Large Array (VLA) and Westerbork Synthesis Radio Telescope (WSRT) observations of the radio afterglow from the gamma-ray burst (GRB) of 2003 March 29 (GRB 030329) taken between 672 and 2032 days after the burst. The EVLA and WSRT data suggest a simple power law decay in the flux at 5 GHz, with no clear signature of any rebrightening from the counter jet. We report an unresolved source at day 2032 of size $1.18\pm0.13$ mas, which we use in conjunction with the expansion rate of the burst to argue for the presence of a uniform, ISM-like circumburst medium. We develop a semi-analytic method to model gamma-ray burst afterglows, and apply it to the 5 GHz light curve to perform burst calorimetry. A limit of $< 0.067$ mas yr$^{-1}$ is placed on the proper motion, supporting the standard afterglow model for gamma-ray bursts.Comment: 24 pages, 5 figure

Characterization of BRD4 during mammalian post-meiotic sperm development

During spermiogenesis, the post-meiotic phase of mammalian spermatogenesis, transcription is progressively repressed as nuclei of haploid spermatids are compacted through a dramatic chromatin reorganization involving hyper-acetylation and replacement of most histones with protamines. Although BRDT functions in transcription and histone removal in spermatids, it is unknown whether other BET family proteins play a role. Immunofluorescence of spermatogenic cells revealed BRD4 in a ring around the nuclei of spermatids containing hyper-acetylated histones. The ring lies directly adjacent to the acroplaxome, the cytoskeletal base of the acrosome, previously linked to chromatin reorganization. The BRD4 ring does not form in acrosomal mutant mice. ChIP sequencing in spermatids revealed enrichment of BRD4 and acetylated histones at the promoters of active genes. BRD4 and BRDT show distinct and synergistic binding patterns, with a pronounced enrichment of BRD4 at spermatogenesis-specific genes. Direct association of BRD4 with acetylated H4 decreases in late spermatids as acetylated histones are removed from the condensing nucleus in a wave following the progressing acrosome. These data provide evidence for a prominent transcriptional role of BRD4 and suggest a possible removal mechanism for chromatin components from the genome via the progressing acrosome as transcription is repressed in response to chromatin condensation during spermiogenesis

Osteoblast-specific deficiency of ectonucleotide pyrophosphatase or phosphodiesterase-1 engenders insulin resistance in high-fat diet fed mice

Supraphysiological levels of the osteoblast‐enriched mineralization regulator ectonucleotide pyrophosphatase or phosphodiesterase‐1 (NPP1) is associated with type 2 diabetes mellitus. We determined the impact of osteoblast‐specific Enpp1 ablation on skeletal structure and metabolic phenotype in mice. Female, but not male, 6‐week‐old mice lacking osteoblast NPP1 expression (osteoblast‐specific knockout [KO]) exhibited increased femoral bone volume or total volume (17.50% vs. 11.67%; p < .01), and reduced trabecular spacing (0.187 vs. 0.157 mm; p < .01) compared with floxed (control) mice. Furthermore, an enhanced ability of isolated osteoblasts from the osteoblast‐specific KO to calcify their matrix in vitro compared to fl/fl osteoblasts was observed (p < .05). Male osteoblast‐specific KO and fl/fl mice showed comparable glucose and insulin tolerance despite increased levels of insulin–sensitizing under‐carboxylated osteocalcin (195% increase; p < .05). However, following high‐fat‐diet challenge, osteoblast‐specific KO mice showed impaired glucose and insulin tolerance compared with fl/fl mice. These data highlight a crucial local role for osteoblast NPP1 in skeletal development and a secondary metabolic impact that predominantly maintains insulin sensitivity

Lamin B1 Depletion in Senescent Cells Triggers Large-Scale Changes in Gene Expression and the Chromatin Landscape

Senescence is a stable proliferation arrest, associated with an altered secretory pathway, thought to promote tumor suppression and tissue aging. While chromatin regulation and lamin B1 down-regulation have been implicated as senescence effectors, functional interactions between them are poorly understood. We compared genome-wide Lys4 trimethylation on histone H3 (H3K4me3) and H3K27me3 distributions between proliferating and senescent human cells and found dramatic differences in senescence, including large-scale domains of H3K4me3- and H3K27me3-enriched “mesas” and H3K27me3-depleted “canyons.” Mesas form at lamin B1-associated domains (LADs) in replicative senescence and oncogene-induced senescence and overlap DNA hypomethylation regions in cancer, suggesting that pre-malignant senescent chromatin changes foreshadow epigenetic cancer changes. Hutchinson-Gilford progeria syndrome fibroblasts (mutant lamin A) also show evidence of H3K4me3 mesas, suggesting a link between premature chromatin changes and accelerated cell senescence. Canyons mostly form between LADs and are enriched in genes and enhancers. H3K27me3 loss is correlated with up-regulation of key senescence genes, indicating a link between global chromatin changes and local gene expression regulation. Lamin B1 reduction in proliferating cells triggers senescence and formation of mesas and canyons. Our data illustrate profound chromatin reorganization during senescence and suggest that lamin B1 down-regulation in senescence is a key trigger of global and local chromatin changes that impact gene expression, aging, and cancer