Measurement of the Excitation Spectrum of a Dipolar Gas in the Macrodroplet Regime.

The excitation spectrum of a cigar-shaped strongly dipolar quantum gas at the crossover from a Bose-Einstein condensate to a trapped macrodroplet is predicted to exhibit peculiar features-a strong upward shift of low momentum excitation energies together with a strong multiband response for high momenta. By performing Bragg spectroscopy over a wide range of momenta, we observe both key elements and also confirm the predicted stiffening of excitation modes when approaching the macrodroplet regime. Our measurements are in good agreement with numerical calculations taking into account finite size effects.

Quantum Droplet States of a Binary Magnetic Gas.

Quantum droplets can emerge in bosonic binary magnetic gases (BMGs) from the interplay of short- and long-ranged interactions, and quantum fluctuations. We develop an extended mean field theory for this system and use it to predict equilibrium and dynamical properties of BMG droplets. We present a phase diagram and characterize miscible and immiscible droplet states. We also show that a single-component self-bound droplet can bind another magnetic component, which is not in the droplet regime, due to the interspecies dipole-dipole interactions. Our results should be realizable in experiments with mixtures of highly magnetic lanthanide atoms.

Droplet Crystal Ground States of a Dipolar Bose Gas.

We show that the ground state of a dipolar Bose gas in a cylindrically symmetric harmonic trap has a rich phase diagram, including droplet crystal states in which a set of droplets arrange into a lattice pattern that breaks the rotational symmetry. An analytic model for small droplet crystals is developed and used to obtain a zero temperature phase diagram that is numerically validated. We show that in certain regimes a coherent low-density halo surrounds the droplet crystal, giving rise to a novel phase with localized and extended features.

Collective Excitations of Self-Bound Droplets of a Dipolar Quantum Fluid.

We calculate the collective excitations of a dipolar Bose-Einstein condensate in the regime where it self-binds into droplets stabilized by quantum fluctuations. We show that the filament-shaped droplets act as a quasi-one-dimensional waveguide along which low-angular-momentum phonons propagate. The evaporation (unbinding) threshold occurring as the atom number N is reduced to the critical value N_{c} is associated with a monopolelike excitation going soft as ε_{0}∼(N-N_{c})^{1/4}. Considering the system in the presence of a trapping potential, we quantify the crossover from a trap-bound condensate to a self-bound droplet.

Minimal skin dose increase in longitudinal rotating biplanar linac-MR systems: examination of radiation energy and flattening filter design.

The magnetic fields of linac-MR systems modify the path of contaminant electrons in photon beams, which alters patient entrance skin dose. Also, the increased SSD of linac-MR systems reduces the maximum achievable dose rate. To accurately quantify the changes in entrance skin dose, the authors use EGSnrc Monte Carlo calculations that incorporate 3D magnetic field of the Alberta 0.5 T longitudinal linac-MR system. The Varian 600C linac head geometry assembled on the MRI components is used in the BEAMnrc simulations for 6 MV and 10 MV beam models and skin doses are calculated at an average depth of 70 µm using DOSXYZnrc. 3D modeling shows that magnetic fringe fields decay rapidly and are small at the linac head. SSDs between 100 and 120 cm result in skin-dose increases of between ~6%-19% and ~1%-9% for the 6 and 10 MV beams, respectively. For 6 MV, skin dose increases from ~10.5% to ~1.5% for field-size increases of 5 × 5 cm(2) to 20 × 20 cm(2). For 10 MV, skin dose increases by ~6% for a 5 × 5 cm(2) field, and decreases by ~1.5% for a 20 × 20 cm(2) field. Furthermore, the proposed reshaped flattening filter increases the dose rate from the current 355 MU min(-1) to 529 MU min(-1) (6 MV) or 604 MU min(-1) (10 MV), while the skin-dose increases by only an additional ~2.6% (all percent increases in skin dose are relative to D max). This study suggests that there is minimal increase in the entrance skin dose and minimal/no decrease in the dose rate of the Alberta longitudinal linac-MR system. The even lower skin dose increase at 10 MV offers further advantages in future designs of linac-MR prototypes.

Number fluctuations of a dipolar condensate: anisotropy and slow approach to the thermodynamic regime.

We present a theory for the number fluctuations of a quasi-two-dimensional (quasi-2D) dipolar Bose-Einstein condensate measured with finite resolution cells. We show that when the dipoles are tilted to have a component parallel to the plane of the trap, the number fluctuations become anisotropic, i.e., depend on the in-plane orientation of the measurement cell. We develop analytic results for the quantum and thermal fluctuations applicable to the cell sizes accessible in experiments. We show that as cell size is increased the thermodynamic fluctuation result is approached much more slowly than in condensates with short range interactions, so experiments would not require high numerical aperture imaging to observe the predicted effect.

MO-A-213AB-02: Redesign of a 6 MV Linear Accelerator Waveguide to Produce Energies Up to 10 MV.

PURPOSE: To investigate the feasibility of producing a short, high-energy linear accelerator for use in a proposed hybrid linear accelerator magnetic resonance imager (linac-MRI). METHODS: A short 6MV waveguide was previously simulated in COMSOL and benchmarked against experiment. The simulated input power is increased from 2.5 to 7.5 MW to reflect replacing the magnetron power source with a commercially available klystron, and the RF fields within the waveguide are calculated. The RF solution is used as an input into PARMELA, an electron-tracking software, to calculate the electron energy and spatial distribution exiting the waveguide. The electric fields within the waveguide are compared with experimental thresholds for electric breakdown within the waveguide to determine the possibility of operation at increased input power. The energy spectrum of the electron beam incident on the target is analyzed for suitability for radiotherapy. Finally, some potential modifications to the simulated cavity dimensions and positioning are discussed, and a preliminary estimate of the effects on the electron distributions are analyzed. RESULTS: When the input power is increased, peak surface electric fields within the waveguide of 215 MV/m are calculated, below the threshold determined by experiment of 240 - 300 MV/m for similar resonant structures. The FWHM of the electron focal spot is shown to be 1.5 times larger than the focal spot from the unmodified waveguide. The maximum electron energy increases from 6.1 to 10.6 MeV and the spread of electron energies is 5 times larger than the original. The modifications to the first cavity are shown to reduce the focal spot and energy spread to be comparable to the unmodified waveguide. CONCLUSIONS: It is feasible to produce a high-energy waveguide that is short enough for use in our linac-MRI. Slight modifications to the existing waveguide design will be required to optimize beam parameters for treatment. ACF Graduate Studentship.

Description of International Caenorhabditis elegans Experiment first flight (ICE-FIRST).

Traveling, living and working in space is now a reality. The number of people and length of time in space is increasing. With new horizons for exploration it becomes more important to fully understand and provide countermeasures to the effects of the space environment on the human body. In addition, space provides a unique laboratory to study how life and physiologic functions adapt from the cellular level to that of the entire organism. Caenorhabditis elegans is a genetic model organism used to study physiology on Earth. Here we provide a description of the rationale, design, methods, and space culture validation of the ICE-FIRST payload, which engaged C. elegans researchers from four nations. Here we also show C. elegans growth and development proceeds essentially normally in a chemically defined liquid medium on board the International Space Station (10.9 day round trip). By setting flight constraints first and bringing together established C. elegans researchers second, we were able to use minimal stowage space to successfully return a total of 53 independent samples, each containing more than a hundred individual animals, to investigators within one year of experiment concept. We believe that in the future, bringing together individuals with knowledge of flight experiment operations, flight hardware, space biology, and genetic model organisms should yield similarly successful payloads.

Caenorhabditis elegans expresses three functional profilins in a tissue-specific manner.

Profilins are actin binding proteins, which also interact with polyphosphoinositides and proline-rich ligands. On the basis of the genome sequence, three diverse profilin homologues (PFN) are predicted to exist in Caenorhabditis elegans. We show that all three isoforms PFN-1, PFN-2, and PFN-3 are expressed in vivo and biochemical studies indicate they bind actin and influence actin dynamics in a similar manner. In addition, they bind poly(L-proline) and phosphatidylinositol 4,5-bisphosphate micelles. PFN-1 is essential whereas PFN-2 and PFN-3 are nonessential. Immunostainings revealed different expression patterns for the profilin isoforms. In embryos, PFN-1 localizes in the cytoplasm and to the cell-cell contacts at the early stages, and in the nerve ring during later stages. During late embryogenesis, expression of PFN-3 was specifically detected in body wall muscle cells. In adult worms, PFN-1 is expressed in the neurons, the vulva, and the somatic gonad, PFN-2 in the intestinal wall, the spermatheca, and the pharynx, and PFN-3 localizes in a striking dot-like fashion in body wall muscle. Thus the model organism Caenorhabditis elegans expresses three profilin isoforms and is the first invertebrate animal with tissue-specific profilin expression.

The sterol modifying enzyme LET-767 is essential for growth, reproduction and development in Caenorhabditis elegans.

The let-767 gene encodes a protein that is similar to mammalian steroid enzymes that are responsible for the reduction of 17-beta hydroxysteroid hormones. Caenorhabditis elegans is incapable of the de novo synthesis of cholesterol. Therefore, this free-living nematode must extract cholesterol from its environment and modify it to form steroid hormones that are necessary for its survival. C. elegans is unable to survive in the absence of supplemental cholesterol, and is therefore sensitive to cholesterol limitation. We show that a mutation in let-767 results in hypersensitivity to cholesterol limitation, supporting the hypothesis that LET-767 acts on a sterol derivative. Furthermore, let-767 mutants exhibit defects in embryogenesis, female reproduction and molting. Although ecdysone is the major molting hormone in insects, there is as yet no evidence for ecdysone synthesis in C. elegans, suggesting that a different hormone is required for molting in C. elegans. Our results suggest that LET-767 modifies a sterol hormone that is required both for embryogenesis and for later stages of development.

Changes in gene expression associated with developmental arrest and longevity in Caenorhabditis elegans.

Gene expression in a developmentally arrested, long-lived dauer population of Caenorhabditis elegans was compared with a nondauer (mixed-stage) population by using serial analysis of gene expression (SAGE). Dauer (152,314) and nondauer (148,324) SAGE tags identified 11,130 of the predicted 19,100 C. elegans genes. Genes implicated previously in longevity were expressed abundantly in the dauer library, and new genes potentially important in dauer biology were discovered. Two thousand six hundred eighteen genes were detected only in the nondauer population, whereas 2016 genes were detected only in the dauer, showing that dauer larvae show a surprisingly complex gene expression profile. Evidence for differentially expressed gene transcript isoforms was obtained for 162 genes. H1 histones were differentially expressed, raising the possibility of alternative chromatin packaging. The most abundant tag from dauer larvae (20-fold more abundant than in the nondauer profile) corresponds to a new, unpredicted gene we have named tts-1 (transcribed telomere-like sequence), which may interact with telomeres or telomere-associated proteins. Abundant antisense mitochondrial transcripts (2% of all tags), suggest the existence of an antisense-mediated regulatory mechanism in C. elegans mitochondria. In addition to providing a robust tool for gene expression studies, the SAGE approach already has provided the advantage of new gene/transcript discovery in a metazoan.

Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing.

RNAi is a gene-silencing phenomenon triggered by double-stranded (ds) RNA and involves the generation of 21 to 26 nt RNA segments that guide mRNA destruction. In Caenorhabditis elegans, lin-4 and let-7 encode small temporal RNAs (stRNAs) of 22 nt that regulate stage-specific development. Here we show that inactivation of genes related to RNAi pathway genes, a homolog of Drosophila Dicer (dcr-1), and two homologs of rde-1 (alg-1 and alg-2), cause heterochronic phenotypes similar to lin-4 and let-7 mutations. Further we show that dcr-1, alg-1, and alg-2 are necessary for the maturation and activity of the lin-4 and let-7 stRNAs. Our findings suggest that a common processing machinery generates guide RNAs that mediate both RNAi and endogenous gene regulation.

MUP-4 is a novel transmembrane protein with functions in epithelial cell adhesion in Caenorhabditis elegans.

Tissue functions and mechanical coupling of cells must be integrated throughout development. A striking example of this coupling is the interactions of body wall muscle and hypodermal cells in Caenorhabditis elegans. These tissues are intimately associated in development and their interactions generate structures that provide a continuous mechanical link to transmit muscle forces across the hypodermis to the cuticle. Previously, we established that mup-4 is essential in embryonic epithelial (hypodermal) morphogenesis and maintenance of muscle position. Here, we report that mup-4 encodes a novel transmembrane protein that is required for attachments between the apical epithelial surface and the cuticular matrix. Its extracellular domain includes epidermal growth factor-like repeats, a von Willebrand factor A domain, and two sea urchin enterokinase modules. Its intracellular domain is homologous to filaggrin, an intermediate filament (IF)-associated protein that regulates IF compaction and that has not previously been reported as part of a junctional complex. MUP-4 colocalizes with epithelial hemidesmosomes overlying body wall muscles, beginning at the time of embryonic cuticle maturation, as well as with other sites of mechanical coupling. These findings support that MUP-4 is a junctional protein that functions in IF tethering, cell-matrix adherence, and mechanical coupling of tissues.

Molecular and functional characterization of a family of rat brain T-type calcium channels.

Voltage-gated calcium channels represent a heterogenous family of calcium-selective channels that can be distinguished by their molecular, electrophysiological, and pharmacological characteristics. We report here the molecular cloning and functional expression of three members of the low voltage-activated calcium channel family from rat brain (alpha(1G), alpha(1H), and alpha(1I)). Northern blot and reverse transcriptase-polymerase chain reaction analyses show alpha(1G), alpha(1H), and alpha(1I) to be expressed throughout the newborn and juvenile rat brain. In contrast, while alpha(1G) and alpha(1H) mRNA are expressed in all regions in adult rat brain, alpha(1I) mRNA expression is restricted to the striatum. Expression of alpha(1G), alpha(1H), and alpha(1I) subunits in HEK293 cells resulted in calcium currents with typical T-type channel characteristics: low voltage activation, negative steady-state inactivation, strongly voltage-dependent activation and inactivation, and slow deactivation. In addition, the direct electrophysiological comparison of alpha(1G), alpha(1H), and alpha(1I) under identical recording conditions also identified unique characteristics including activation and inactivation kinetics and permeability to divalent cations. Simulation of alpha(1G), alpha(1H), and alpha(1I) T-type channels in a thalamic neuron model cell produced unique firing patterns (burst versus tonic) typical of different brain nuclei and suggests that the three channel types make distinct contributions to neuronal physiology.

LET-413 is a basolateral protein required for the assembly of adherens junctions in Caenorhabditis elegans.

Epithelial cells are polarized, with apical and basal compartments demarcated by tight and adherens junctions. Proper establishment of these subapical junctions is critical for normal development and histogenesis. We report the characterization of the gene let-413 which has a critical role in assembling adherens junctions in Caenorhabditis elegans. In let-413 mutants, adherens junctions are abnormal and mislocalized to more basolateral positions, epithelial cell polarity is affected and the actin cytoskeleton is disorganized. The LET-413 protein contains one PDZ domain and 16 leucine-rich repeats with high homology to proteins known to interact with small GTPases. Strikingly, LET-413 localizes to the basolateral membrane. We suggest that LET-413 acts as an adaptor protein involved in polarizing protein trafficking in epithelial cells.

let-756, a C. elegans fgf essential for worm development.

In vertebrates, Fibroblast Growth Factors (FGFs) and their receptors are involved in various developmental and pathological processes, including neoplasia. The number of FGFs and their large range of activities have made the understanding of their precise functions difficult. Investigating their biology in other species might be enlightening. A sequence encoding a putative protein presenting 30-40% identity with the conserved core of vertebrate FGFs has been identified by the C. elegans sequencing consortium. We show here that this gene is transcribed and encodes a putative protein of 425 amino acids (aa). The gene is expressed at all stages of development beyond late embryogenesis, peaking at the larval stages. Loss-of-function mutants of the let-756 gene are rescued by the wild type fgf gene in germline transformation experiments. Two partial loss-of-function alleles, s2613 and s2809, have a mutation that replaces aa 317 by a stop. The truncated protein retains the FGF core but lacks a C-termins portion. These worms are small and develop slowly into clear and scrawny, yet viable and fertile adults. A third allele, s2887, is inactivated by an inversion that disrupts the first exon. It causes a developmental arrest early in the larval stages. Thus, in contrast to the other nematode fgf gene egl-17, let-756/fgf is essential for worm development.

UNC-60B, an ADF/cofilin family protein, is required for proper assembly of actin into myofibrils in Caenorhabditis elegans body wall muscle.

The Caenorhabditis elegans unc-60 gene encodes two functionally distinct isoforms of ADF/cofilin that are implicated in myofibril assembly. Here, we show that one of the gene products, UNC-60B, is specifically required for proper assembly of actin into myofibrils. We found that all homozygous viable unc-60 mutations resided in the unc-60B coding region, indicating that UNC-60B is responsible for the Unc-60 phenotype. Wild-type UNC-60B had F-actin binding, partial actin depolymerizing, and weak F-actin severing activities in vitro. However, mutations in UNC-60B caused various alterations in these activities. Three missense mutations resulted in weaker F-actin binding and actin depolymerizing activities and complete loss of severing activity. The r398 mutation truncated three residues from the COOH terminus and resulted in the loss of severing activity and greater actin depolymerizing activity. The s1307 mutation in a putative actin-binding helix caused greater activity in actin-depolymerizing and severing. Using a specific antibody for UNC-60B, we found varying protein levels of UNC-60B in mutant animals, and that UNC-60B was expressed in embryonic muscles. Regardless of these various molecular phenotypes, actin was not properly assembled into embryonic myofibrils in all unc-60 mutants to similar extents. We conclude that precise control of actin filament dynamics by UNC-60B is required for proper integration of actin into myofibrils.

Identification and characterization of a serine hydroxymethyltransferase isoform in Caenorhabditis briggsae.

In the nematode Caenorhabditis elegans, the maternal effect lethal gene mel-32 encodes a serine hydroxymethyltransferase isoform. Since interspecies DNA comparison is a valuable tool for identifying sequences that have been conserved because of their functional importance or role in regulating gene activity, mel-32(SHMT) genomic DNA from C. elegans was used to screen a genomic library from the closely related nematode Caenorhabditis briggsae. The C. briggsae genomic clone identified fully rescues the Mel-32 phenotype in C. elegans, indicating functional and regulatory conservation. Computer analysis reveals that CbMEL-32(SHMT) is 92% identical (97% similar) to CeMEL-32(SHMT) at the amino acid level over the entire length of the protein (484 amino acids), whereas the coding DNA is 82.5% identical (over 1455 nucleotides). Several highly conserved non-coding regions upstream and downstream of the mel-32(SHMT) gene reveal potential regulatory sites that may bind trans-acting protein factors.