Search

Hypothesis: A lack of contraction of cerebral microarterioles to Ang II (“resilience”) depends on cyclooxygenase (COX) and lipocalin type prostaglandin D sythase L-PGDS producing PGD2 that activates prostaglandin D type 1 receptors (DP1Rs) and nitric oxide synthase (NOS). Materials & Methods: Contractions were assessed in isolated, perfused vessels and NO by fluorescence microscopy. Results: The mRNAs of penetrating intraparenchymal cerebral microarterioles versus renal afferent arterioles were >3000-fold greater for L-PGDS and DP1R and 5-fold for NOS III and COX 2. Larger cerebral arteries contracted with Ang II. However, cerebral microarterioles were entirely unresponsive but contracted with endothelin 1 and perfusion pressure. Ang II contractions were evoked in cerebral microarterioles from COX1 –/– mice or after blockade of COX2, L-PGDS or NOS and in deendothelialized vessels but effects of deendothelialization were lost during COX blockade. NO generation with Ang II depended on COX and also was increased by DP1R activation. Conclusion: The resilience of cerebral arterioles to Ang II contractions is specific for intraparenchymal microarterioles and depends on endothelial COX1 and two products that are metabolized by L-PGDS to generate PGD2 that signals via DP1Rs and NO.

A cascaded lattice Boltzmann (LB) approach based on central moments and multiple relaxation times to simulate thermal convective flows, which are driven by buoyancy forces and/or swirling effects, in the cylindrical coordinate system with axial symmetry is presented. In this regard, the dynamics of the axial and radial momentum components along with the pressure are represented by means of the 2D Navier-Stokes equations with geometric mass and momentum source terms in the pseudo Cartesian form, while the evolutions of the azimuthal momentum and the temperature field are each modeled by an advection-diffusion type equation with appropriate local source terms. Based on these, cascaded LB schemes involving three distribution functions are formulated to solve for the fluid motion in the meridian plane using a D2Q9 lattice, and to solve for the azimuthal momentum and the temperature field each using a D2Q5 lattice. The geometric mass and momentum source terms for the flow fields and the energy source term for the temperature field are included using a new symmetric operator splitting technique, via pre-collision and post-collision source steps around the cascaded collision step for each distribution function. These result in a particularly simple and compact formulation to directly represent the effect of various geometric source terms consistently in terms of changes in the appropriate zeroth and first order moments. Simulations of several complex buoyancy-driven thermal flows and including rotational effects in cylindrical geometries using the new axisymmetric cascaded LB schemes show good agreement with prior benchmark results for the structures of the velocity and thermal fields as well as the heat transfer rates given in terms of the Nusselt numbers., Comment: 49 pages,12 figures

A cascaded central moment based lattice Boltzmann (LB) method for solving low Mach number thermal convective flows with source terms in two-dimensions in a double distribution function framework is presented. For the passive temperature field, which satisfies the convection diffusion equation (CDE) with a source term to represent internal/external local heat source, a new cascaded collision kernel is presented. Due to the use of a single conserved variable in the thermal energy equation, the cascaded structure in its collision operator begins from the first order moments and evolves to higher order moments. This is markedly different from the collision operator for the fluid flow equations, constructed in previous work, where the cascaded formulation starts at the second order moments in its collision kernel. A consistent implementation of the spatially and temporally varying source terms in the thermal cascaded LB method representing the heat sources in the CDE that maintains second order accuracy via a variable transformation is discussed. The consistency of the thermal cascaded LB method including a source term for the D2Q9 lattice with the macroscopic convection–diffusion equation is demonstrated by means of a Chapman–Enskog analysis. The new model is tested on a set of benchmark problems such as the thermal Poiseuille flow, thermal Couette flow with either wall injection or including viscous dissipation and natural convection in a square cavity. The validation study shows that the thermal cascaded LB method with source term is in very good agreement with the analytical solutions or numerical results reported for the benchmark problems. In addition, the numerical results show that our new thermal cascaded LB model maintains second order accuracy.

Simulation of multiphase flows require coupled capturing or tracking of the interfaces in conjunction with the solution of fluid motion often occurring at multiple scales. We will present unified cascaded LB methods based on central moments for the solution of the incompressible two-phase flows at high density ratios and for capturing of the interfacial dynamics. Based on a modified continuous Boltzmann equation (MCBE) for two-phase flows, where a kinetic transformation to the distribution function involving the pressure field is introduced to reduce the associated numerical stiffness at high density gradients, a central moment cascaded LB formulation for computing the fluid motion will be constructed. In this LB scheme, the collision step is prescribed by the relaxation of various central moments to their equilibria that are reformulated in terms of the pressure field obtained via matching to the continuous equilibria based on the transformed Maxwell distribution. Furthermore, the differential treatments for the effects of the source term representing the change due to the pressure field and of the source term due to the interfacial tension force and body forces appearing in the MCBE on different moments are consistently accounted for in this cascaded LB solver that computes the pressure and velocity fields. In addition, another cascaded LB scheme via modified equilibria will be developed to solve for the interfacial dynamics represented by a phase field model based on the conservative Allen-Cahn equation. Based on numerical simulations of a variety of two-phase flow benchmark problems at high density ratios and involving the effects of surface tension and its tangential gradients (Marangoni stresses), we will validate our unified cascaded LB approach and also demonstrate improvements in numerical stability., Comment: This work was presented at the 71st Annual Meeting of the APS Division of Fluid Dynamics (DFD), Atlanta, Georgia, Nov. 2018 (http://meetings.aps.org/link/BAPS.2018.DFD.L31.7) with travel support from NSF. The first author's Ph.D. dissertation [52] is based, in part, on the research contribution presented in this work

Heterogeneous nucleate boiling over a flat surface has been studied through complete numerical simulations. During the growth and departure of the vapor bubble, the interface is tracked following a coupled level-set and volume of fluid approach. A microlayer evaporation model similar to Sato and Niceno [“A depletable microlayer model for nucleate pool boiling,” J. Comput. Phys. 300, 20–52 (2015)] has been deployed in this investigation. A detailed study of the changes in microlayer structure as a result of different modes of boiling scenario has been performed. The departure diameter is found to increase with an increase in substrate superheat. The predicted departure diameter has been compared with the available experimental and analytical results. A power-law curve has been obtained for depicting the growth rate of bubble depending on the degree of superheat at the wall. The space–time averaged wall-heat flux at different values of superheat temperature of substrate is obtained. Bubble growth during subcooled boiling at a low and intermediate subcooled degree has been observed through direct numerical simulations. The variations in bubble dynamics after departure in saturated and subcooled liquid states have been compared.

We have developed a new generation of low noise, broadband feeds for the Allen Telescope Array at the Hat Creek Observatory in Northern California. The new feeds operate over the frequency range 0.9 to 14 GHz. The noise temperatures of the feeds have been substantially improved by cooling the entire feed structure as well as the low noise amplifiers to 70 K. To achieve this improved performance, the new feeds are mounted in glass vacuum bottles with plastic lenses that maximize the microwave transmission through the bottles. Both the cooled feeds and their low noise amplifiers produce total system temperatures that are in the range 25-30 K from 1 GHz to 5 GHz and 40-50 K up to 12.5 GHz., Comment: 16 pages, 11 figures, accepted to Publications of the Astronomical Society of the Pacific

PurposeThe purpose of this paper is to present a numerical approach for investigating different phenomena during multiple liquid drop impact on air‐water interface.Design/methodology/approachThe authors have used the coupled level‐set and volume‐of‐fluid (CLSVOF) method to explore the different phenomena during multi‐drop impact on liquid‐liquid interface. Complete numerical simulation is performed for two‐dimensional incompressible flow, which is described in axisymmetric coordinates.FindingsDuring drop pair impact at very low impact velocities, the process of partial coalescence is observed where the process of pinch off is different than single drop impact. At higher impact velocities, phenomena such as bubble entrapment are observed.Originality/valueIn this paper, a new approach has been developed to simulate consecutive drop impact on a liquid pool.

Plants, algae, and fungi are essential for nearly all life on earth. Through photosynthesis, plants and algae convert solar energy to chemical energy in the form of organic compounds that sustains essentially all life on earth. In addition, plants and algae convert the carbon dioxide produced by respiring organisms to oxygen that is needed for respiration. Fungi decompose complex organic compounds produced by respiring organisms so that molecules can be recycled in photosynthesis and respiration. Plants, algae, and fungi have one important feature in common, their cells have walls. Expansive growth and its regulation are central to the life and development of plant, algal, and fungal cells, i.e. cells with walls. In recent decades there has been an explosion of information relevant to expansive growth of cells with walls. Mathematical models have been constructed in an attempt to organize and evaluate this information, to gain insight, to evaluate hypotheses, and to assist in the selection and development of new experimental studies. In this article some of the mathematical models constructed to study expansive growth of cells with walls are reviewed. It is nearly impossible to review all relevant research conducted in this area. Instead, the review focuses on the development of mathematical equations that have been used to model expansive growth, morphogenesis, and growth rate regulation of cells with walls. Also, relevant experimental findings are reviewed, conceptual models are presented, and suggestions for future research are proposed. The authors have attempted to provide an overview that is accessible to researchers that are not working in this field.

Two-phase flows involving phase change are ubiquitous in a diverse range of scientific and technological applications. There has been great recent interest in the enhancement of boiling heat transfer processes by means of additives such as surfactants. Surfactants can influence boiling through convection currents in the bulk fluids as a result of changes in the surface tension caused by local surfactant concentration due their adsorption/desorption from the bulk regions. This can result in changes in bubble release patterns and higher heat transfer rates if such changes lead to higher rate of vapor formation. We intend to study this effect in the context of film boiling. Our computational approach augments the CLSVOF method with bulk energy and diffusion equations along with a phase change model and an interface surfactant model. The challenge here is to accurately calculate the tangential gradients of the interfacial surfactant concentration in the presence of discontinuous bulk concentration gradients near the interface. We discuss a simplified model in which the interfacial surfactant concentration is always in equilibrium with the changing bulk concentrations and then present validation results to assess the accuracy of this approach. Finally, initial studies of surfactant enhanced film boiling will be presented and interpreted.

The complete solution of a two-phase flow problem requires the solution of appropriate partial differential equations (PDEs) of mass, momentum, and energy in the region occupied by the vapor and in the region occupied by the liquid. The moving interface between each phasic region requires the specification of additional interface conditions. These additional conditions are jump conditions imposed by the mass, momentum, and energy balances at the interface and additional interface ‘constitutive’ equations. These additional interface constitutive equations can also be thought of as internal interface boundary conditions that must be imposed on the PDEs on each side of the interface to secure a well posed problem. It is well known that the characteristic equations in any hyperbolic system give a complete picture of the required boundary conditions or interface shock conditions. In this paper, the limiting form of a set of characteristic equations will be used to determine the nature of the phasic interface conditions that are required in a compressible, viscous, conducting fluid at a mass transfer interface. The analysis will show that the traditional interface modeling constitutive equations are insufficient in number and hence lead to multiple solutions and therefore to an ill-posed problem. The source of the insufficient number of interface conditions will be discussed.

The presence of surfactants in two-phase flows results in the transport and adsorption of surfactants to the interface, and the resulting local interfacial concentration significantly influences the surface tension between the liquid and vapor phases in a fluid undergoing phase change. This computational study is aimed at understanding and elucidating the mechanisms of enhanced flows and thermal transport processes in film boiling due to the addition of surfactants. A change in surface tension results in a change in the critical Rayleigh-Taylor wavelength leading to different bubble release patterns and a change in the overall heat transfer rates. Due to the presence of surfactants, an additional transport mechanism of the Marangoni convection arises from the resulting tangential gradients in the surfactant concentration along the phase interface. Our computational approach to study such phenomena consists of representing the interfacial motion by means of the coupled level set-volume-of-fluid method, the fluid motion via the classical marker-and-cell approach, as well as representations for the bulk transport of energy and surfactants, in conjunction with a phase change model and an interfacial surfactant model. Using such an approach, we perform numerical simulations of surfactant-laden single mode as well as multiple mode film boiling and study the effect of surfactants on the transport processes in film boiling, including bubble release patterns, vapor generation rates, and heat transfer rates at different surfactant concentrations. The details of the underlying mechanisms will be investigated and interpreted.The presence of surfactants in two-phase flows results in the transport and adsorption of surfactants to the interface, and the resulting local interfacial concentration significantly influences the surface tension between the liquid and vapor phases in a fluid undergoing phase change. This computational study is aimed at understanding and elucidating the mechanisms of enhanced flows and thermal transport processes in film boiling due to the addition of surfactants. A change in surface tension results in a change in the critical Rayleigh-Taylor wavelength leading to different bubble release patterns and a change in the overall heat transfer rates. Due to the presence of surfactants, an additional transport mechanism of the Marangoni convection arises from the resulting tangential gradients in the surfactant concentration along the phase interface. Our computational approach to study such phenomena consists of representing the interfacial motion by means of the coupled level set-volume-of-fluid method, the...

A planar simulation of film boiling and bubble formation in water at 373°C, 219 bar on an isothermal horizontal surface was performed by using a volume of fluid (VOF) based interface tracking method. The complete Navier-Stokes equations and thermal energy equations were solved in conjunction with a interface mass transfer model. The numerical method takes into account the effect of temperature on the transportive thermal properties (thermal conductivity and specific heat) of vapor, effects of surface tension, the interface mass transfer and the corresponding latent heat. The computations provided a good insight into film boiling yielding quantitative information on unsteady periodic bubble release patterns and on the spatially and temporally varying film thickness. The computations also predicted the transport coefficients on the horizontal surface, which were greatly influenced by the variations in fluid properties, compared to calculations with constant properties.

This article presents a numerical method and simulations of film boiling including conjugate heat transfer. A volume-of-fluid (VOF) interface tracking method is augmented with a mass transfer model and a model for surface tension. The bulk fluids are viscous, conducting, and incompressible. We explore film boiling on a horizontal surface and we consider the effect of the energy exchange between a solid wall and the boiling fluid during saturated horizontal film boiling.

We present a high-resolution image of the region near HL Tau in 13CO (1-0) over a region of 3' made with the BIMA array, supplemented by data from the NRAO 12 m telescope to include emission structures with low spatial frequencies. We find evidence for a shell of dimensions ~2' ? 15 (~0.08 ? 0.06 pc), with XZ Tau being the closest known source to its center. The 13CO map is consistent with an expanding bubble that has blown out on the far side from earth. Portions of the bubble wall are seen in optical scattered light. HL Tau is situated in the bubble wall; the evacuated region corresponds to the truncation in the reflection nebula northeast of HL Tau. Although it is thought that a remnant protostellar envelope is still infalling onto HL Tau, the existence of the expanding bubble makes it difficult to interpret the geometry and kinematics of the HL Tau circumstellar material. Our results demonstrate the importance of including low-spatial frequency emission for the interpretation of interferometer maps.

We have observed the ionized gas in the star-forming region W49N with the National Radio Astronomy Observatory Very Large Array (VLA) at 13 mm and 7 mm, and with the Berkeley Illinois Maryland Association (BIMA) Array at 3.3 mm. These observations vary in resolution from 0045 to 035 (500 AU to 4000 AU at a distance of 11.4 kpc). In addition, we have used the VLA to observe water maser emission towards the bright W49N:G sources over a wide velocity range from -435 to 435 km s-1. The high-resolution continuum observations reveal the morphologies in the ultracompact sources; most of the sources at 0.045'' resolution appear to have shell or ring morphologies. The 3.3 mm emission observed with the BIMA array is dominated by free-free emission in all of the compact sources. There is no evidence for any spectral breaks corresponding to the emergence of a dust component. Of the seven bright sources in W49N for which multifrequency flux densities have been measured, four are observed to have rising spectral indices, with values ranging from α = 0.3-1.1 and three are observed to be flat (Sν ∝ να). Those sources with rising spectral indices (A, B1, B2, G1, and G2) also have the broadest radio recombination lines, with ΔVFWHM > 45 km s-1 in the H66α line (De Pree, Mehringer, & Goss). High-resolution 1.3 cm continuum images made at the same time as the water maser observations have been used to align the maser positions with the high-resolution 7 mm continuum to within 005. The maser positions are closely associated with the G1/G2 sources. The outflow traced by the water masers (Gwinn, Moran & Reid) appears to be centered within 0.2'' of the G2 peak, the brightest continuum source in the region, but it remains unclear whether this source drives the outflow.

This paper presents a numerical method directed towards the simulation of flows with mass transfer due to changes of phase. We use a volume of fluid (VOF) based interface tracking method in conjunction with a mass transfer model and a model for surface tension. The bulk fluids are viscous, conducting, and incompressible. A one-dimensional test problem is developed with the feature that a thin thermal layer propagates with the moving phase interface. This test problem isolates the ability of a method to accurately calculate the thermal layers responsible for driving the mass transfer in boiling flows. The numerical method is tested on this problem and then is used in simulations of horizontal film boiling.

The molecular basis of enhanced ischemic tissue survival in flaps preconditioned by surgical delay is poorly understood. Because elevated expression of so-called heat shock or stress proteins has been shown to protect tissues/organs against ischemic injury, the authors examined whether the levels of the most highly induced stress protein-hsp72-were elevated in delayed muscle flaps using a rat muscle flap model. Bilateral latissimus dorsi muscle flaps based on the thoracodorsal vessels were elevated in 16 male Sprague-Dawley rats. For each animal, one side was selected randomly to undergo preconditioning by surgical delay for a 7-day period prior to elevation. Delay was accomplished by preserving the thoracodorsal pedicle and a single large distal intercostal perforating vessel. After bilateral flap elevation, latissimus dorsi tissue was harvested from proximal, central, and distal flap segments 0, 1, 3, and 7 days postoperatively (N = 4 for each group), and was analyzed for the expression of hsp72 via Western blot analysis. At the time of harvest, flap viability was assessed by staining with nitroblue tetrazolium. Flap perfusion was measured prior to muscle elevation and harvest using laser Doppler flowmetry. The results demonstrate that delayed muscle flaps had significantly greater total perfusion (p0.05) and survival (p0.03) 1, 3, and 7 days after elevation compared with the acutely elevated control tissue. Western blot analysis revealed that tissues harvested from the delayed flaps expressed substantially higher levels of hsp72 compared with the acutely elevated control samples. Segmental analysis also revealed a proximalmiddledistal expression of hsp72 in the delayed flaps (p0.05). Flap preconditioning by surgical delay increases the expression of hsp72. Moreover, regional differences in hsp72 gene expression are associated with differences in perfusion and survival of delayed muscle flaps. These results indicate that hsp72 may play a substantial role in mediating the delay phenomenon.

We report on the spectroscopic identification and the long awaited redshift measurement of the heavily obscured, gravitationally lensed radio source PKS 1830-211, which was first observed as a radio Einstein ring. The NE component of the doubly imaged core is identified, in our infrared spectrum covering the wavelength range 1.5-2.5 microns, as an impressively reddened quasar at z=2.507. Our redshift measurement, together with the recently measured time delay (Lovell et al.), means that we are a step closer to determining the Hubble constant from this lens. Converting the time delay into the Hubble constant by using existing models leads to high values for the Hubble constant. Since the lensing galaxy lies very close to the center of the lensed ring, improving the error bars on the Hubble constant will require not only a more precise time delay measurement, but also very precise astrometry of the whole system., 11 pages, 2 figures, Accepted ApJL

In vitro transcription/translation of actin cDNA and analysis of the translation products by native-PAGE was used to study the maturation pathway of actin. During the course of actin synthesis, several distinct actin-containing species were observed and the composition of each determined by immunological procedures. After synthesis of the first approximately 145 amino acids, the nascent ribosome-associated actin chain binds to the recently identified heteromeric chaperone protein, prefoldin (PFD). PFD remains bound to the relatively unfolded actin polypeptide until its posttranslational delivery to cytosolic chaperonin (CCT). We show that alpha- and beta-tubulin follow a similar maturation pathway, but to date find no evidence for an interaction between PFD and several noncytoskeletal proteins. We conclude that PFD functions by selectively targeting nascent actin and tubulin chains pending their transfer to CCT for final folding and/or assembly.

The quasi-static viscoelastic response of polymeric materialsis investigated utilizing constitutive models based on fractionalcalculus. Time-based fractional calculus analysis techniques areemphasized. Analytic solutions to quasi-static boundary value problemsin which the viscoelastic behavior is characterized by thefour-parameter fractional calculus-based solid model are given. Varioussets of data from the literature are fit with existing and newfractional calculus-based constitutive equations.

We investigate the history and geometry of mass loss in three carbon-rich evolved stars, CIT 6, AFGL 618, and IRAS 21282+5050, using observations of the 12CO J = 1-0 line emission and a simple radiative transfer code to model these observations. Combining data from the Berkeley-Illinois-Maryland Association millimeter array and the NRAO 12 m, we have constructed full synthesis data cubes of the 12CO J = 1-0 line emission from CIT 6, AFGL 618, and IRAS 21282+5050 with angular resolutions of approximately 8'', 3'', and 4'', respectively. We find clumpy envelopes with zero-order structures of bright cores, surrounded by lower surface brightness halos in all three sources; however, the contrast between the core and halo is greater for AFGL 618 than for IRAS 21282+5050 and CIT 6. The total flux line profile for CIT 6 has a parabolic shape, in contrast to the flat-topped shape found by all previous single-dish observations that have resolved the envelope, which we measure to be at least 100'' in diameter. The 12CO emission in AFGL 618 has a similar east-west bipolar morphology as its optical reflection nebulosity, although on a much larger scale (90'' × 60''). The bulk of molecular gas in AFGL 618 participates in a symmetric expansion; however, a significant east-west bipolar outflow appears at the heart of the core with detected velocities up to ~70 km s-1. A blueshifted component (~-40 km s-1) of the this bipolar outflow is observed in absorption against the continuum source in AFGL 618. We resolve a central hole in IRAS 21282+5050 with a size, 6'', slightly larger than its H II region. A bright ring of 12CO emission surrounds this central hole, and a ~70'' diameter halo surrounds this ring. The ring appears broken in position-velocity cuts due to a significant blueshifted self-absorption of the gas. We develop a simple radiative transfer code that assumes spherically symmetric expansion to model the zero-order core-halo structures observed in these sources. We assume a temperature power-law profile with respect to radius and fit a power-law index between -0.7 and -0.8 for all three sources. The fitted density profiles with respect to radius reflect the observed differences in the core-halo structures and suggest differences in the mass-loss histories of the three sources. The models of both CIT 6 and IRAS 21282+5050 are consistent with constant mass-loss rates of (6 ± 2) × 10-6 and (6 ± 4) × 10-5 M☉ yr-1, respectively. The model of AFGL 618 suggests two phases of mass loss: an older asymptotic giant branch (AGB) wind lasting ~8000 yr when the mass-loss rate decreased from (2 ± 1) × 10-4 to (3 ± 1) × 10-5 M☉ yr-1 and a more recent superwind lasting ~4000 yr when the mass-loss rate increased to (2 ± 1) × 10-4 M☉ yr-1.

This paper presents a numerical method directed towards the local simulation of axisymmetric vapor bubble growth. We use an interface tracking method in conjunction with a finite volume method on a moving unstructured mesh. We allow metastable bulk states and assume the interface exists in thermal and chemical equilibrium. The bulk fluids are viscous, conducting, and compressible. The control volume continuity, momentum and energy equations are modified in the presence of a phase interface to include surface tension and discontinuous pressure and velocity. A solid wall model is included to allow for conjugate heat transfer modes.

One of the most powerful methods for generating similarity solutions to problems in fluid mechanics and heat transfer is the group-theory method; it is also one of the easiest to apply. However, because of the apparent difficulty and obscurity of the underlying mathematics it is rarely mentioned in anything but advanced graduate seminars in these areas. This is unfortunate, as it is actually one of the most physically based and computationally simple of the methods available for obtaining such solutions. In this paper we give a presentation of this method which will make these group-theoretic techniques accessible and useful to advanced undergraduates and beginning graduate students. Several examples, both standard and unusual, are also given.

Folding of newly synthesized proteins in vivo is believed to be facilitated by the cooperative interaction of a defined group of proteins known as molecular chaperones. We investigated the direct interaction of chaperones with nascent polypeptides in the cytosol of mammalian cells by multiple methods. A new approach using a polyclonal antibody to puromycin allowed us to tag and capture a population of truncated nascent polypeptides with no bias as to the identity of the bound chaperones. In addition, antibodies that recognize the cytosolic chaperones hsp70, CCT (TRiC), hsp40, p48 (Hip), and hsp90 were compared on the basis of their ability to coprecipitate nascent polypeptides, both before and after chemical cross-linking. By all three approaches, hsp70 was found to be the predominant chaperone bound to nascent polypeptides. The interaction between hsp70 and nascent polypeptides is apparently dynamic under physiological conditions but can be stabilized by depletion of ATP or by cross-linking. The cytosolic chaperonin CCT was found to bind primarily to full-length, newly synthesized actin, and tubulin. We demonstrate and caution that nascent polypeptides have a propensity for binding many proteins nonspecifically in cell lysates. Although current models of protein folding in vivo have described additional components in contact with nascent polypeptides, our data indicate that the hsp70 and, perhaps, the hsp90 families are the predominant classes of molecular chaperones that interact with the general population of cytosolic nascent polypeptides.

We present subarcsecond resolution imaging of the λ = 2.7 mm continuum emission from the young, embedded system L1551 IRS 5 using the nine-element, high-resolution configuration of the BIMA array. The observed emission arises from two compact sources separated by 035, coinciding with the two sources seen at λ = 2 cm and λ = 1.3 cm. When the high-resolution data are combined with data from two compact configurations, L1551 IRS 5 is argued to consist of a protobinary system separated by ~50 AU with individual circumstellar disks, a circumbinary structure, and a large-scale envelope. The characteristic masses of the components are 0.024 M☉ for the northern circumstellar disk, 0.009 M☉ for the southern circumstellar disk, 0.04 M☉ for the circumbinary material, and 0.28 M☉ for the envelope.

We have obtained a subarcsecond image of the disk associated with the T Tauri star HL Tau at a wavelength of 2.7 mm using the new high-resolution capability of the BIMA Array. The disk is elongated with a deconvolved Gaussian source size of 10 ± 02 × 05 ± 02, implying a semimajor axis of 70 ± 15 AU for a distance of 140 pc; the minor axis may be unresolved. The position angle of the major axis (125° ± 10°) is orthogonal to the axis of the optical jet. The disk centroid is coincident with the VLA λ = 3.6 cm source position and nearly coincident with recent measurements of the near-infrared emission peak. The λ = 2.7 mm images, along with previous interferometric measurements at λ = 0.87 mm and flux measurements from 10 μm to 1.3 cm, are well fitted by a simple power-law disk model with a shallow radial dependence to the surface density [Σ(r) ∝ r0 to r-1], an outer radius between 90 and 160 AU, and a dust opacity law proportional to ν1.

This paper presents a moving mesh, two-dimensional finite volume method suitable for tracking interfaces across which there is mass transfer. We consider liquid and vapor phases of single component fluids separated by a phase interface in an evolving flow field. Metastable bulk states are allowed (as are superheated vapor and subcooled liquid bulk states) while the interface is assumed to exist in thermal and chemical equilibrium. Mass transfer occurs at the interface, driven by the local flow conditions. The interface is tracked by nodes representing the liquid and vapor sides at the same spatial location. The interface motion is found from the solution of the coupled interfacial conditions and bulk fluid equations. The bulk fluids are considered as viscous, conducting, and compressible fluids necessitating the use of the continuity, momentum and energy equations in the bulk regions. The control volume continuity, momentum and energy equations are modified in the presence of a phase interface to include surface properties using a simple interface model with surface tension and surface energy. Simple simulations are presented illustrating the method.

Thromboxane A2 (TxA2) or its stable mimetic U-46,619 can increase the generation of arachidonate metabolites. Therefore, these studies were designed to investigate the role of prostaglandins, TxA2, and leukotrienes in the renal vascular response to U-46,619. Anesthetized rats were studied during a basal period and during an intra-aortic infusion of vehicle or U-46,619 (1 micrograms/kg per minute). U-46,619 reduced the GFR and the RBF without changing the mean arterial pressure or the femoral vascular resistance. All of the effects of U-46,619 were blocked by pretreatment with the TxA2/prostaglandin H2 receptor antagonist SQ-29,548. Pretreatment with the cyclo-oxygenase inhibitor indomethacin did not modify the renal vascular response to U-46,619. However, pretreatment with the TxA2 synthesis inhibitor UK-38,485 or with the leukotriene D4/E4 antagonist LY-163,443 markedly blunted the U-46,619-induced increase in renal vascular resistance and the decrease in GFR. These results indicate that the renal vascular response to U-46,619 is receptor mediated and is promoted by TxA2 and leukotriene D4/E4.

We incubated in vitro translated precursor of medium-chain acyl-CoA dehydrogenase (MCAD) with isolated rat liver mitochondria and fractionated the solubilized mitochondria on gel filtration. After a 5-min import into mitochondria, MCAD was recovered exclusively as a high molecular weight (hMr) complex (700,000), while after a 10-min import, it was recovered mainly in the hMr complex and mature tetramer, with a small amount in monomer. Either a further 15-min chase or exposure to ATP caused a marked decrease of MCAD in the hMr complex and an increase in the mature tetramer in comparable amounts, suggesting that the hMr complex was the precursor of tetramer. No monomer was detected in either case. Using specific antibodies, we have shown that the hMr complex represented a complex of MCAD and heat-shock protein 60 (hsp60), and, that upon import into mitochondria, unfolded MCAD first formed a transient complex with mitochondrial heat-shock protein 70 (hsp70mit) and then transferred to hsp60 to complete its folding into an assembly-competent conformation. We also examined the assembly of K304E MCAD, which is a prevalent variant enzyme among patients with MCAD deficiency. The assembly of the K304E into its tetrameric form was severely impaired. The binding of K304E with hsp70mit and its transfer from hsp70mit to hsp60 were normal. However, the hsp60 complex of K304E was much more stable than the wild-type counterpart upon a 15-min chase or exposure to ATP, suggesting that the folding in, or the transfer of K304E subunit to tetramer from, the complex with hsp60 was impaired.

The development of millimeter and submillimeter interferometers was basically motivated by the discovery, in the late 1960s and early 1970s, that trace amounts of molecular gas in the interstellar medium could be detected through millimeter-wave spectral line emission (cf Rank et al 1971). The observed lines reflected the presence of unexpectedly large amounts of molecular hydrogen, H_2 organized into giant molecular clouds where star formation takes place in the Milky Way and in other galaxies (e.g. Sanders et aI 1984). A wide variety of millimeter-wave molecular lines have also been identified in the circumstellar shells around evolved stars (cf Loup et al 1993). The intensities and Doppler shifts of these mm-wave spectral lines provide information about the density, temperature, kinematics, and chemical state of the gas. In addition, interstellar and circumstellar dust can be studied through observations of millimeter-wave continuum radiation. The success of centimeter-wavelength interferometers such as the VLA in producing fundamental new science argued that millimeter-wavelength astronomy would also benefit from the high angular resolution provided by interferometers.

Molecular chaperones belonging to heat shock protein families have been identified as prominent antigens in the immune response to a wide variety of infections. Recognition of such highly conserved antigens may contribute to protective immunity but, in some circumstances, may also have pathological autoimmune consequences. Recognition of chaperones may be an inherent feature of the immune system. Peptide mapping experiments revealed an overlap between hsp 70-binding sites and immunodominant regions of three protein antigens, consistent with a possible functional activity for molecular chaperones in the processing and presentation of peptides during class II-restricted T lymphocyte responses. A functional role for molecular chaperones in antigen processing may be a factor which contributes to their immunogenicity.

An enzyme-linked immunosorbent assay (ELISA) for measurement of levels of heat shock proteins 73 and 72 (HSP73/72) in cultured cells and tissues is described. The assay involves detection of HSP73/72 in cell homogenates in 96-well plates using a specific monoclonal antibody. The assay has been used to explore the relationship between the amount of HSP73/72 in a cell and its response to heat shock, both before and after the development of thermotolerance. Six mammalian cell lines with differing responses to heat were characterized with respect to their response to heat treatments at 44°C and concentrations of HSP73/72. Contrary to the widely expressed idea that the amount of HSP73/72 dictates the degree of heat resistance, no positive correlation between levels of HSP73/72 and heat resistance was found for the six lines tested here: if one particular line, a mutant selected for heat resistance, was excluded from the analysis, there was a negative correlation between HSF'73/72 levels and heat resistance. A ...

Because endogenous thromboxane A2 (TXA2) potentiates the tubuloglomerular feedback response (TGF), we studied the mechanism of action of TXA2 by using a stable TXA2/prostaglandin (PG) H2 mimetic, U-46,619. Intravenous infusion of U-46,619 at 100 ng.kg-1.min-1 reduced the GFR and the single-nephron (SN)GFR measured from the distal tubule (macula densa function intact), whereas the SNGFR measured from the proximal tubule (macula densa function interrupted) was not changed consistently. 10-100-fold higher rates of infusion of U-46,619 were required to raise blood pressure or femoral vascular resistance. The regulation of glomerular capillary pressure (PGC) by TGF was assessed in anesthetized rats from changes in proximal stop flow pressure (PSF) and/or SNGFR during perfusion of the loop of Henle (LH) with artificial tubular fluid (ATF). Orthograde loop perfusion and retrograde perfusion of U-46,619 into the macula densa segment reduced PSF. Responses to luminal U-46,619 were blunted by a TXA2-PGH2 receptor antagonist. Orthograde loop perfusions with luminal U-46,619 increased net Cl absorption, whereas coperfusion with furosemide (10(-4) M) blunted the response to U-46,619 by 68%. These data indicated that the luminal U-46,619 might increase the signal for TGF activation by increasing Cl reabsorption in macula densa cells. However, since 80 +/- 4% of [3H]U-46,619 perfused via the LH was reabsorbed peritubular capillaries (PTC) were perfused with U-46,619 to test additional extra-luminal actions. PTC perfusion with U-46,619 again increased TGF by reducing PSF selectively only while macula densa function was intact during perfusion of the LH with ATF. Conclusions: (a) TGF is potentiated by U-46,619 given systematically, via the lumen of the LH by orthograde or retrograde perfusions or via the PTC; (b) at the lower doses tested, reduction of PGC and SNGFR by U-46,619 depends on tubular fluid delivery and reabsorption by the macula densa; (c) potentiation of TGF by U-46,619 entails preglomerular vasoconstriction which may be elicited in part by an increased signal due to increased net chloride reabsorption in the LH and presumably macula densa cells and by an increased sensitivity of the arteriole to macula densa-derived signals; (d) activation of TGF may contribute to the selective vasoconstriction of the renal vascular bed by low doses of U-46,619.

A large number of protein and molecular markers have been identified that delineate the early stages of human B cell activation and proliferation. In contrast, few if any molecules are transiently expressed precisely as activated B cells stop proliferating and undergo growth arrest. We demonstrate that the low molecular weight heat shock protein (hsp28) exhibits unique induction kinetics that specifically demarcates this interval. After mitogenic activation of unstimulated splenic B cells, hsp28 protein and phosphorylation transiently increase coinciding precisely with the peak of cellular proliferation and the onset of growth arrest. Although most neoplastic B cells constitutively express hsp28, three cell lines were identified that were hsp28-. No differences in phenotype or growth kinetics were detected between hsp28+ and hsp28- neoplastic B cells demonstrating that hsp28 expression is not essential for cell growth. However, when treated with phorbol ester or heat shock, these hsp28- cell lines synthesize hsp28 followed by the onset growth arrest. The consistency with which hsp28 induction transiently delineates the interval from peak proliferation to the onset of growth arrest suggests hsp28 itself is likely to be involved in regulating this process.

BACKGROUND To test the hypothesis that the heat shock response is associated with improved myocardial salvage after myocardial ischemia and reperfusion, rats treated with prior whole-body hyperthermia and 24 hours of recovery (n = 26) or 20 minutes of ischemic pretreatment and 8 hours of recovery (n = 24) and control rats (n = 27, n = 24, for hyperthermic and ischemic pretreatment, respectively) were subjected to 35 minutes of left coronary artery (LCA) occlusion and 120 minutes of reperfusion. METHODS AND RESULTS Although ventricular samples from rats subjected to either hyperthermia (n = 7) or ischemic pretreatment (n = 6) all showed induction of HSP72 (heat shock protein), Western blot analysis revealed significantly greater amounts of HSP72 in samples obtained from rats subjected to hyperthermia compared with those from rats subjected to ischemic pretreatment. Control rats (n = 7) showed no significant presence of myocardial HSP72. After 35 minutes of LCA occlusion and 2 hours of reperfusion, infarct size was significantly reduced in heat-shocked rats compared with controls (8.4 +/- 1.7%, n = 26 versus 15.5 +/- 1.9%, n = 27; p = 0.007; mean +/- SEM; infarct mass/left ventricular mass x 100). There were no significant differences in left ventricular (LV) systolic pressure, heart rate, LV dP/dt, or rate-pressure product between heat-shocked (n = 11) and control (n = 14) rats during the ischemic period. There were no differences in infarct size between ischemically pretreated and control rats subjected to 35 minutes of ischemia and reperfusion (9.7 +/- 2.1%, n = 23 versus 10.0 +/- 2.1, n = 24; p = NS). CONCLUSIONS In this model of ischemia and reperfusion, prior heat shock was associated with significantly improved myocardial salvage after 35 minutes of LCA occlusion and reperfusion. This improved salvage was correlated with marked HSP72 induction and was independent of the hemodynamic determinants of myocardial oxygen supply and myocardial oxygen demand during the ischemic period. In contrast, mild HSP72 induction by ischemic pretreatment was not associated with improved myocardial salvage after myocardial ischemia and reperfusion. Thus, the absolute levels of HSP72 may be important in conferring protection from ischemic injury in this animal model.

Two populations of intercalated cells, type A and type B, are present in the rat cortical collecting duct (CCD). Type A cells are involved in proton secretion and contain an apical H(+)-adenosinetriphosphatase (ATPase) and a basolateral Cl(-)-HCO3- exchanger. Type B cells are believed to be involved in HCO3- secretion, which is mediated by a Cl(-)-HCO3- exchange process and is Cl- dependent. The aim of this study was to examine the morphological and immunocytochemical response of type B intercalated cells in the rat to increased delivery of Cl- to the CCD. This was accomplished by chronic infusion of a loop diuretic, bumetanide (30 mg.kg body wt-1.day-1), via an osmotic minipump, and simultaneous administration of 0.9% sodium chloride in the drinking water for 6 days. The kidneys were preserved by in vivo perfusion with a periodate-lysine-paraformaldehyde fixative and processed for horseradish peroxidase and protein A gold immunocytochemistry, using rabbit polyclonal antibodies against carbonic anhydrase II, proton ATPase, and band 3 protein. Chronic infusion of bumetanide in combination with a high salt intake was associated with significant changes in the intercalated cells. Type B cells were increased in size and exhibited numerous apical microvilli, increased basolateral membrane area, and marked cytoplasmic and basolateral labeling for H(+)-ATPase. In contrast, type A cells were small and had sparse apical microprojections. H(+)-ATPase immunolabeling was observed primarily over apical tubulovesicles, and there was decreased basolateral immunolabeling for band 3 protein and occasional labeling for band 3 in lysosome-like structures. These observations support the hypothesis that increased delivery of Cl- to the CCD is associated with stimulation of type B intercalated cells to secrete HCO3-. The observations in type A cells are consistent with the cells being in a resting or inactivated state.

To better understand assembly mechanisms of progesterone receptor (PR) complexes, we have developed a cell-free system for studying PR interactions with the 90- and 70-kDa heat shock proteins (hsp90 and hsp70), and we have used this system to examine requirements for hsp90 binding to PR. Purified chick PR, free of hsp90 and immobilized on an antibody affinity resin, will rebind hsp90 in rabbit reticulocyte lysate when several conditions are met. These include: 1) absence of progesterone, 2) elevated temperature (30 degrees C), 3) presence of ATP, and 4) presence of Mg2+. We have obtained maximal hsp90 binding to receptor when lysate is supplemented with 3 mM MgCl2 and an ATP-regenerating system. ATP depletion of lysate by dialysis or by enzymatic means blocks hsp90 binding to PR; likewise, addition of EDTA to lysate blocks hsp90 binding, but binding is restored by the addition of excess Mg2+. Addition to lysate of monoclonal antibody against hsp70 inhibits hsp90 binding to PR and destabilizes preformed complexes. Stabilization of hsp90-receptor complexes also requires ATP, indicating that ATP and hsp70 are needed to form and to maintain hsp90 complexes. Hormone-dependent activation of reconstituted receptor complexes was also examined. The addition of progesterone to the reticulocyte lysate promotes dissociation of hsp90 and hsp70 from the receptor. This also appears to require ATP and dissociation is most efficient in the presence of an ATP-regenerating system. In conclusion, these studies indicate that PR-hsp90 complexes do not self-assemble; instead, assembly is probably a multistep process requiring ATP and other cellular factors.

In mammalian cells, two of the so-called heat shock (hsp) or stress proteins are components of the mitochondria. One of these, hsp 58, is a member of the bacterial GroEL family, whereas the other, glucose-regulated protein (grp) 75, represents a member of the hsp 70 family of stress proteins. Owing to previous studies implicating a role for both the hsp 70 and GroEL families in facilitating protein maturation events, we used the method of native immunoprecipitation to examine whether hsp 58 and grp 75 might interact with other proteins of the mitochondria. In cells pulse-labeled with [35S]-methionine, a significant number of newly synthesized mitochondrial proteins co-precipitated with either hsp 58 or grp 75. Such interactions appeared transient. For example, providing the pulse-labeled cells a subsequent chase period in the absence of radiolabel resulted in a reduction of co-precipitating proteins. If the pulse-chase labeling experiments were performed in the presence of an amino acid analogue, somewhat different results were obtained. Specifically, although many of the newly synthesized and analogue-containing proteins again were observed to co-precipitate with grp 75, the interactions did not appear transient, but instead were stable. Under steady-state labeling conditions, we also observed a portion of hsp 58 and grp 75 in an apparent complex with one another. On addition of ATP, the complex was dissociated. Accompanying this dissociation was the concomitant autophosphorylation of grp 75. On the basis of these observations, as well as previous studies examining the structure/function of the hsp 70 and GroEL proteins, we suspect that both hsp 58 and grp 75 interact with and facilitate the folding and assembly of proteins as they enter into the mitochondria.

There are many important scientific problems to be attacked in the submillimeter wavelength region including the astrophysics of star formation, the dynamics of protoplanetary systems, the physics of interstellar gas, mass loss from stars, supernovae, the chemical evolution of galaxies, the star formation rates in galaxies, the astrophysics of active galactic nuclei, the deuterium abundance in different astrophysical environments, and the distribution of the cosmic background radiation. However, to effectively explore this wavelength range requires going into space since atmospheric absorption precludes most observations from the ground. As in most areas of astronomy, the twin needs for sensitivity and high redsolution indicate use of an imaging interferometer, but the needed baselines of a few tens-of-meters require a large physical structure. The planned Space Station will provide, for the first time, a platform which is large enough to accommodate a forefront submillimeter synthesis instrument. Such a telescope would open an entirely new wavelength regime to astronomy with the attendant possibilities for unexpected new discoveries. A submillimeter array would also be technically well suited for operation on the Space Station. Second-of-are resolution at submillimeter wavelengths requires only relatively short baselines; pointing accuracy and tracking stability requirements are relatively crude being determined by the single dish size rather than the array resolution; radio frequency interference (RFI) susceptibility is very low due to the large frequency separation from normal communications bands; emissions from co-orbiting debris, dust, gas, and water vapour are uncorrelated between interferometer elements; baseline stability requirements, while severe, are less stringent than for optical/IR interferometers and can almost certainly be satisfied for existing phase correction and phaseless image restoration techniques; and the technology for the dishes, mounts, receivers, LO/IF systems, and correlators either exists or is a reasonable extrapolation of what already is available on the ground. We consider the applications and possible design of a Space Station based submillimeter array which could be mounted along the main (‘Y’) axis of the Space Station and use orbital revolution and precession to produce high-resolution synthesis mapping in much the same way ground-based linear arrays do by Earth rotation synthesis.