Coexisting crystal and liquid-like properties in a 2D long-range self-consistent model.

A two-dimensional class of mean-field models serving as a minimal frame to study long-range interaction in two space dimensions is considered. In the case of an anisotropic mixed attractive-repulsive interaction, an initially spatially homogeneous cold fluid is dynamically unstable and evolves towards a quasi-stationary state in which the less energetic particles get trapped into clusters forming a Bravais-like lattice, mimicking a crystalline state. Superimposed to this, one observes in symplectic numerical simulations a flux of slightly more energetic particles channeling through this crystalline background. The resultant system combines the rigidity features of a solid, as particles from a displaced core are shown to snap back into place after a transient, and the dynamical diffusive features of a liquid for the fraction of channeling and free particles. The combination of solid and liquid properties is numerically observed here within the classical context. The quantum transposition of the model may be experimentally reached using the latest ultracold atoms techniques to generate long-range interactions.

The clinical utility of CA 19-9 in pancreatic adenocarcinoma: diagnostic and prognostic updates.

CA 19-9 and CEA are the most commonly used biomarkers for diagnosis and management of patients with pancreatic cancer. Since the original compendium by Steinberg in 1990, numerous studies have reported the use of CA 19-9 and, to a lesser extent, CEA in the diagnosis of pancreatic cancer. Here we update an evaluation of the accuracy of CA 19-9 and CEA, and, unlike previous reviews, focus on discrimination between malignant and benign disease instead of normal controls. In 57 studies involving 3,285 pancreatic carcinoma cases, the combined sensitivity of CA 19-9 was 78.2% and in 37 studies involving 1,882 cases with benign pancreatic disease the specificity of CA 19-9 was 82.8%. From the combined analysis of studies reporting CEA, the sensitivity was 44.2% (1,324 cases) and the specificity was 84.8% (656 cases). These measurements more appropriately reflect the expected biomarker accuracy in the differential diagnosis of patients with periampullary diseases. We also present a summary of the use of CA 19-9 as a prognostic tool and evaluate CA 19-9 diagnostic and prognostic utility in a 10-year, single institution experience.

SU-E-T-477: Influence of Eye Size on Radiation Absorbed Dose Delivered to Non- Targeted Tissues during Stereotactic Radiosurgery for Age-Related Macular Degeneration.

PURPOSE: This work determines how variations in eye size will influence the radiation absorbed dose delivered to non-targeted tissues within the eye during stereotactic radiosurgery of age-related macular degeneration (AMD) using the IRay™ treatment. METHODS: Stylized models of the eye were created with axial lengths of 20, 22, 24, 26, and 28mm. Each model was based upon the reference eye model from NCRP Report 130 and then scaled appropriately for each axial length. Models were incorporated with MCNPX radiation transport code in order to simulate the three beam IRay™ delivery system. Simulation results were assessed for both the mean absorbed dose and dose-volume histograms (DVH) for both target (macula) and non- targeted eye tissues, including the lens, retina, central retinal artery, and optic nerve. RESULTS: For each of the three beams, an average dose of 8Gy was delivered to the macula resulting in a total average dose of 24Gy for each eye model. The lens of the eye received a total average dose ranging from 146 to 189mGy, with the larger doses occurring in the smaller eye models since the beams traverse through the sciera closer to the limbus. The distal tip (1.5mm) of the central retinal artery received a total average dose ranging from 499 to 567mGy, with the larger doses occurring in the larger eye models due to increased scatter resulting from longer tissue path length to the nominal target. The optic nerve received a total average dose ranging from 207 to 225mGy, with the larger doses occurring in the smaller eye models. CONCLUSIONS: The small variation in dose to the lens, central retinal artery, and optic nerve suggests that eye size does not significantly affect radiation dose to non-targeted eye tissues. This work was sponsored by Oraya Therapeutics.

Stochastic treatment of finite-N effects in mean-field systems and its application to the lifetimes of coherent structures.

A stochastic treatment yielding to the derivation of a general Fokker-Planck equation is presented to model the slow convergence toward equilibrium of mean-field systems due to finite-N effects. The thermalization process involves notably the disintegration of coherent structures that may sustain out-of-equilibrium quasistationary states. The time evolution of the fraction of particles remaining close to a mean-field potential trough is analytically computed. This indicator enables to estimate the lifetime of coherent structures and thermalization time scale in mean-field systems.

Early out-of-equilibrium beam-plasma evolution.

We solve analytically the out-of-equilibrium initial stage that follows the injection of a radially finite electron beam into a plasma at rest and test it against particle-in-cell simulations. For initial large beam edge gradients and not too large beam radius, compared to the electron skin depth, the electron beam is shown to evolve into a ring structure. For low enough transverse temperatures, the filamentation instability eventually proceeds and saturates when transverse isotropy is reached. The analysis accounts for the variety of very recent experimental beam transverse observations.

Síndrome de Hamman, revisión bibliográfica y presentación de un caso / Hamman syndrome, literature review and case report

Introducción: El neumomediastino se define como la presencia de aires en el espacio mediastinito. Desde su introducción en la literatura por Hamman se ha podido determinar su origen en la lesión alveolar por barotrauma. Generalmente tiene un curso benigno afectando a hombres entre los 20-30 años de edad.Objetivo: Revisión bibliográfica y presentación de caso.Lugar de aplicación: Hospital polivalente de alta complejidad.Caso Clínico: Varón de 22 años que consulta por dolor en hemotórax derecho, alteración del tono de vos y enfisema subcutáneo cervical. Al examen físico se constata signo de Hamman. Se solicita radiografía de tórax haciéndose diagnóstico de neumomediastino. Se instaura tratamiento médico con buena evolución sin requerir tratamiento quirúrgico.Discusión: El neumomediastino es una patología poco frecuente de curso generalmente benigno. Su diagnóstico obliga a descartar otras causas como la perforación esofágica o lesión del árbol traqueobronquial. Su tratamiento implica medidas de sostén y en algunos casos oxígeno a altas dosis, reservando el tratamiento quirúrgico a las complicaciones como el taponamiento cardíaco o neumotórax hipertensivo.

Interplay of collisions with quasilinear growth rates of relativistic electron-beam-driven instabilities in a superdense plasma.

We focus attention on the rapidly growing electromagnetic instabilities arising in the interaction of intense and relativistic electron beams (REB) with supercompressed thermonuclear fuel. REB-target system is considered neutralized in charge and current with a distribution function including beam and target temperatures. The electromagnetic filamentation (Weibel) instability is first considered analytically in a linear approximation. Relevant growth rates parameters then highlight density ratios between target and particle beams, as well as transverse temperatures. Significant refinements include mode-mode coupling and collisions with target electrons. The former qualify the so-called quasilinear (weakly turbulent) approach. Usually, it produces significantly lower growth rates than the linear ones. Collisions enhance them slightly for kc/omega(p) < 1, and dampen them strongly for kc/omega(p) < 1. In a low temperature target plasma, intrabeam scattering also contributes to the instability taming, while keeping it close to zero in a warm plasma. Our numerical exploration provides further support to the cone-angle configuration (Osaka experiment) with REB penetrating close to the dense core of superdense deuterium + tritium fuel.

Electromagnetic instabilities for relativistic beam-plasma interaction in whole k space: nonrelativistic beam and plasma temperature effects.

For the system formed by a relativistic electron beam and its plasma return current, we investigate the effects of both transverse and parallel beam and plasma temperatures on the linear stability of collective electromagnetic modes. We focus on nonrelativistic temperatures and wave-vector orientations ranging from two-stream to filamentation instabilities. Water-bag distributions are used to model temperature effects and we discuss their relevance. Labeling Theta(k) the angle between the beam and the wave vector, one or two critical angles Theta(c,i) are determined exactly and separate the k space into two parts. Modes with Theta(k) < Theta(c) =min ( Theta(c,i)) are quasilongitudinal and poorly affected by any kind of temperature. Modes having Theta(k) > Theta(c) are very sensitive to transverse beam and plasma parallel temperatures. Also, parallel plasma temperature can trigger a transition between the beam-dependent filamentation instability (Theta(k) =pi/2) and the plasma-temperature-dependent Weibel instability so that two-stream, filamentation, and Weibel instabilities are eventually closely connected to each other. The maximum growth rate being reached for a mode with Theta(k) < Theta(c), no temperature of any kind can significantly reduce it in the nonrelativistic temperature regime.

Characterization of the initial filamentation of a relativistic electron beam passing through a plasma.

The linear instability that induces a relativistic electron beam passing through a plasma with return current to filament transversely is often related to some filamentation mode with the wave vector normal to the beam or confused with Weibel modes. We show that these modes may not be relevant in this matter and identify the most unstable mode on the two-stream or filamentation branch as the main trigger for filamentation. This sets both the characteristic transverse and longitudinal filamentation scales in the nonresistive initial stage.

Collective electromagnetic modes for beam-plasma interaction in the whole k space.

We investigate the linear stability of the system formed by an electron beam and its return plasma current within a general framework, namely, for any orientation of the wave vector k with respect to the beam and without any a priori assumption on the orientation of the electric field with respect to k . We apply this formalism to three configurations: cold beam and cold plasma, cold beam and hot plasma, and cold relativistic beam and hot plasma. We proceed to the identification and systematic study of the two branches of the electromagnetic dispersion relation. One pertains to Weibel-like beam modes with transverse electric proper waves. The other one refers to electric proper waves belonging to the plane formed by k and the beam, it divides between Weibel-like beam modes and a branch sweeping from longitudinal two-stream modes to purely transverse filamentation modes. For this latter branch, we thoroughly investigate the intermediate regime between two-stream and filamentation instabilities for arbitrary wave vectors. When some plasma temperature is allowed for, the system exhibits a critical angle at which waves are unstable for every k . Besides, in the relativistic regime, the most unstable mode on this branch is reached for an oblique wave vector. This study is especially relevant to the fast ignition scenario as its generality could help clarify some confusing linear issues of present concern. This is a prerequisite towards more sophisticated nonlinear treatments.

Stimulation of in vivo angiogenesis by cytokine-loaded hyaluronic acid hydrogel implants.

Crosslinked hyaluronic acid (HA) hydrogels were evaluated for their ability to elicit new microvessel growth in vivo when preloaded with one of two cytokines, vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF). HA film samples were surgically implanted in the ear pinnas of mice, and the ears retrieved 7 or 14 days post implantation. Histologic analysis showed that all groups receiving an implant demonstrated significantly more microvessel density than control ears undergoing surgery but receiving no implant (p < 0.01). Moreover, aqueous administration of either growth factor produced substantially more vessel growth than an HA implant with no cytokine. However, the most striking result obtained was a dramatic synergistic interaction between HA and VEGF. Presentation of VEGF in crosslinked HA generated vessel density of NI = 6.7 at day 14, where NI is a neovascularization index defined below, more than twice the effect of the sum of HA alone (NI = 1.8) plus VEGF alone (NI=1.3). This was twice the vessel density generated by co-addition of HA and bFGF (NI=3.4, p<0.001). New therapeutic approaches for numerous pathologies could be notably enhanced by the localized, synergistic angiogenic response produced by release of VEGF from crosslinked HA films.

Dynamical analysis of the nonlinear growth of the m = n = 1 resistive internal mode.

A dynamical analysis is presented that self-consistently takes into account the motion of the critical layer, in which the magnetic field reconnects, to describe how the m=n=1 resistive internal kink mode develops in the nonlinear regime. The amplitude threshold marking the onset of strong nonlinearities due to a balance between convective and mode coupling terms is identified. We predict quantitatively the early nonlinear growth rate of the m=n=1 mode below this threshold.

Long-time discrete particle effects versus kinetic theory in the self-consistent single-wave model.

The influence of the finite number N of particles coupled to a monochromatic wave in a collisionless plasma is investigated. For growth as well as damping of the wave, discrete particle numerical simulations show an N-dependent long time behavior resulting from the dynamics of individual particles. This behavior differs from the one due to the numerical errors incurred by Vlasov approaches. Trapping oscillations are crucial to long time dynamics, as the wave oscillations are controlled by the particle distribution inhomogeneities and the pulsating separatrix crossings drive the relaxation towards thermal equilibrium.

The Hox cofactor and proto-oncogene Pbx1 is required for maintenance of definitive hematopoiesis in the fetal liver.

Pbx1 is the product of a proto-oncogene originally discovered at the site of chromosomal translocations in acute leukemias. It binds DNA as a complex with a broad subset of homeodomain proteins, but its contributions to hematopoiesis have not been established. This paper reports that Pbx1 is expressed in hematopoietic progenitors during murine embryonic development and that its absence results in severe anemia and embryonic lethality at embryonic day 15 (E15) or E16. Definitive myeloerythroid lineages are present in Pbx1(-/-) fetal livers, but the total numbers of colony-forming cells are substantially reduced. Fetal liver hypoplasia reflects quantitative as well as qualitative defects in the most primitive multilineage progenitors and their lineage-restricted progeny. Hematopoietic stem cells from Pbx1(-/-) embryos have reduced colony-forming activity and are unable to establish multilineage hematopoiesis in competitive reconstitution experiments. Common myeloid progenitors (CMPs), the earliest known myeloerythroid-restricted progenitors, are markedly depleted in Pbx1(-/-) embryos at E14 and display clonogenic defects in erythroid colony formation. Comparative cell-cycle indexes suggest that these defects result largely from insufficient proliferation. Megakaryocyte- and erythrocyte-committed progenitors are also reduced in number and show decreased erythroid colony-forming potential. Taken together, these data indicate that Pbx1 is essential for the function of hematopoietic progenitors with erythropoietic potential and that its loss creates a proliferative constriction at the level of the CMP. Thus, Pbx1 is required for the maintenance, but not the initiation, of definitive hematopoiesis and contributes to the mitotic amplifications of progenitor subsets through which mature erythrocytes are generated. (Blood. 2001;98:618-626)

Cardiovascular overexpression of transforming growth factor-beta(1) causes abnormal yolk sac vasculogenesis and early embryonic death.

Transforming growth factor-beta(1) (TGF-beta(1)) is expressed in the adult and embryonic vasculature; however, the biological consequences of increased vascular TGF-beta(1) expression remain controversial. To establish an experimental setting for investigating the role of increased TGF-beta(1) in vascular development and disease, we generated transgenic mice in which a cDNA encoding a constitutively active form of TGF-beta(1) is expressed from the SM22alpha promoter. This promoter fragment directs transgene expression to smooth muscle cells of large arteries in late-term embryos and postnatal mice. We confirmed the anticipated pattern of SM22alpha-directed transgene expression (heart, somites, and vasculature of the embryo and yolk sac) in embryos carrying an SM22alpha-beta-galactosidase transgene. SM22alpha- beta-galactosidase transgenic mice were born at the expected frequency (13%); however, nearly all SM22alpha-TGF-beta(1) transgenic mice died before E11.5. SM22alpha-TGF-beta(1) transgenic embryos identified at E8.5 to E10.5 had growth retardation and both gross and microscopic abnormalities of the yolk sac vasculature. Overexpression of TGF-beta(1) from the SM22alpha promoter is lethal at E8.5 to E10.5, most likely because of yolk sac insufficiency. Investigation of the consequences of increased vascular TGF-beta(1) expression in adults may require a conditional transgenic approach. Moreover, because the SM22alpha promoter drives transgene expression in the yolk sac vasculature at a time when embryonic survival is dependent on yolk sac function, use of the SM22alpha promoter to drive expression of "vasculoactive" transgenes may be particularly likely to cause embryonic death.

The 23 S rRNA environment of ribosomal protein L9 in the 50 S ribosomal subunit.

Ribosomal protein L9 consists of two globular alpha/beta domains separated by a nine-turn alpha-helix. We examined the rRNA environment of L9 by chemical footprinting and directed hydroxyl radical probing. We reconstituted L9, or individual domains of L9, with L9-deficient 50 S subunits, or with deproteinized 23 S rRNA. A footprint was identified in domain V of 23 S rRNA that was mainly attributable to N-domain binding. Fe(II) was tethered to L9 via cysteine residues introduced at positions along the alpha-helix and in the C-domain, and derivatized proteins were reconstituted with L9-deficient subunits. Directed hydroxyl radical probing targeted regions of domains I, III, IV, and V of 23 S rRNA, reinforcing the view that 50 S subunit architecture is typified by interwoven rRNA domains. There was a striking correlation between the cleavage patterns from the Fe(II) probes attached to the alpha-helix and their predicted orientations, constraining both the position and orientation of L9, as well as the arrangement of specific elements of 23 S rRNA, in the 50 S subunit.

Administration of Flk2/Flt3 ligand induces expansion of human high-proliferative potential colony-forming cells in the SCID-hu mouse.

The effects of Flk2/Flt3 ligand (FL) administration on human hematopoiesis were investigated using SCID-hu mice transplanted with human fetal bone fragments. Treatment with recombinant human FL induced significant increases in the frequencies of the high-proliferative potential colony-forming cells and low-proliferative potential colony-forming cells in steady-state human bone marrow. FL also promoted the expansion of high-proliferative potential colony-forming cells and low-proliferative potential colony-forming cells in the human bone marrow during the recovery phase after irradiation, which was evident in increases in the frequencies as well as in the absolute numbers of colony-forming cells. Furthermore, higher percentages of CD33+ CD15- cells were found in the marrows treated with FL as compared to that of controls, indicating that FL hastened the recovery of at least some aspect of myelopoiesis after irradiation. These results indicate that FL induces the expansion of primitive hematopoietic progenitor cells in vivo and, therefore, may be useful in treating patients to promote an early hematopoietic recovery after cytoablative therapies.

Release factor RF-3 GTPase activity acts in disassembly of the ribosome termination complex.

RF3 was initially characterized as a factor that stimulates translational termination in an in vitro assay. The factor has a GTP binding site and shows sequence similarity to elongation factors EF-Tu and EF-G. Paradoxically, addition of GTP abolishes RF3 stimulation in the classical termination assay, using stop triplets. We here show GTP hydrolysis, which is only dependent on the simultaneous presence of RF3 and ribosomes. Applying a new termination assay, which uses a minimessenger RNA instead of separate triplets, we show that GTP in the presence of RF3 stimulates termination at rate-limiting concentrations of RF1. We show that RF3 can substitute for EF-G in RRF-dependent ribosome recycling reactions in vitro. This activity is GTP-dependent. In addition, excess RF3 and RRF in the presence of GTP caused release of nonhydrolyzed fmet-tRNA. This supports previous genetic experiments, showing that RF3 might be involved in ribosomal drop off of peptidyl-tRNA. In contrast to GTP involvement of the above reactions, stimulation of termination with RF2 by RF3 was independent of the presence of GTP. This is consistent with previous studies, indicating that RF3 enhances the affinity of RF2 for the termination complex without GTP hydrolysis. Based on our results, we propose a model of how RF3 might function in translational termination and ribosome recycling.

The importance of base pairing in the penultimate stem of Escherichia coli 16S rRNA for ribosomal subunit association.

The influence of base pairing in the penultimate stem of Escherichia coli 16S rRNA (defined as nt 1409-1491) on ribosome function has been addressed by the construction of mutations in this region of rRNA. Two sets of mutations were made on either side of a structurally conserved region in the penultimate stem that disrupted base pairing, while a third set of mutations replaced the wild-type sequence with other base pair combinations. The effects of these mutations were analyzed in vivo and in vitro . The mutations that disrupted base pairing caused significant increases in cell doubling times as well as a severe subunit association defect and a modest increase in frame shifting and stop codon read-through. Restoration of base pairing restored wild-type growth rates, decoding and subunit association, indicating that base pairing in this region is essential for proper ribosome function.