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Residual systemic inflammation and mucosal immune dysfunction persist in people living with HIV, despite treatment with combined anti-retroviral therapy, but the underlying immune mechanisms are poorly understood. Here we report that the altered immune landscape of the oral mucosa of HIV-positive patients on therapy involves increased TLR and inflammasome signaling, localized CD4+ T cell hyperactivation, and, counterintuitively, enrichment of FOXP3+ T cells. HIV infection of oral tonsil cultures in vitro causes an increase in FOXP3+ T cells expressing PD-1, IFN-γ, Amphiregulin and IL-10. These cells persist even in the presence of anti-retroviral drugs, and further expand when stimulated by TLR2 ligands and IL-1β. Mechanistically, IL-1β upregulates PD-1 expression via AKT signaling, and PD-1 stabilizes FOXP3 and Amphiregulin through a mechanism involving asparaginyl endopeptidase, resulting in FOXP3+ cells that are incapable of suppressing CD4+ T cells in vitro. The FOXP3+ T cells that are abundant in HIV-positive patients are phenotypically similar to the in vitro cultured, HIV-responsive FOXP3+ T cells, and their presence strongly correlates with CD4+ T cell hyper-activation. This suggests that FOXP3+ T cell dysregulation might play a role in the mucosal immune dysfunction of HIV patients on therapy., Anti-retroviral treatment does not fully resolve mucosal dysfunction and systemic inflammation in HIV infected individuals. Authors show here that an unusual population of regulatory T cells, distinguished by Amphiregulin expression and the incapability to suppress CD4 T cells might contribute to disrupted oral immune protection in HIV patients.

The 2200 magnets used in the CEBAF beam transport system have each undergone testing of their magnetic fields. Results of these measurements will be reported. /spl int/Bdl profiles measurements (with a precision of /spl ap/10/sup -5/) for the 270 major solid-core dipoles used a multi-turn stretched wire with a reference magnet; the range of /spl int/Bdl for a given (1, 2, or 3 m) dipole family was /spl plusmn/5/spl times/10/sup -4/. The /spl sim/700 quadrupole magnets' /spl int/B/sub n/dl (1/spl les/n/spl les/16, R=R/sub pole/) values were measured with an accuracy of 0.01% of the quadrupole field component using a multi-turn "Halbach" bucked coil for 20% of the magnets and a reference magnet for all. They had (/spl int/B/sub 6/dl)/(/spl int/B/sub 2/dl) >

High energy photons ( E γ ⩾30 MeV) have been measured in coincidence with light particles observed in a multidetector array for the 40 Ar+ 51 V system at a bombarding energy of E A =65 MeV . Double differential cross sections were obtained as a function of the midrapidity charge representation of the centrality of the collision. The inverse slope parameter increases with centrality more strongly than predicted by a BUU model.

A reaction filter of nearly 4π sr geometry is presented. Its ability to tag heavy-ion collisions according to their centrality is established by a comparison of experimental data with computer simulations and BUU model calculations in which events of known impact parameter are filtered by the instrumental acceptance. On the one hand, energy spectra of light charged particles from reactions of 20 Ne at 35 and 45 MeV/nucleon with a NaF target show little dependence of their high-energy slopes upon the relative impact parameters determined by this technique. On the other hand, spectra from 20 Ne on 45 Sc and 197 Au targets display increasing slopes with increasing centrality. Such a difference between symmetric and asymmetric systems is consistent with the formation of a “participant” zone.

Ionization counters employing Bragg curve spectroscopy have been constructed for use in a 4π geometry. These detectors compare very favorably in terms of both energy and charge resolution with small solid angle devices. These detectors have a large dynamic range because they are backed by scintillation detectors, and are thus capable of detecting and identifying particles with energies from 1 MeV/nucleon up to 200 MeV/nucleon.

Using the MSU 4π Array with the NSCL K1200 Superconducting Cyclotron we have measured an excitation function for 40 Ar+ 51 V from 35 to 100 MeV/nucleon. We have observed a minimum in collective flow around 82 MeV/nucleon which marks the transition from attractive to repulsive scattering. Multi-fragment emission is observed to occur sequentially in reactions at 35 MeV/nucleon. As the beam energy is raised, the emission becomes more simultaneous. Using azimuthal asymmetries, we have extracted rotation-like phenomena. This signal for rotation is strong at 35 MeV/nucleon and nearly disappears as the beam energy is raised to 85 MeV/nucleon.

The Michigan State University 4{pi} array has been used to select central-impact-parameter events from the reaction {sup 40}Ar+{sup 51}V at incident energies from 35 to 85 MeV/nucleon. The event shape in momentum space is an observable which is shown to be sensitive to the dynamics of the fragmentation process. A comparison of the experimental event-shape distribution to sequential- and simultaneous-decay predictions suggests that a transition in the breakup process may have occurred. At 35 MeV/nucleon, a sequential-decay simulation reproduces the data. For the higher energies, the experimental distributions fall between the two contrasting predictions.

We first discuss the progress in linear optics, in particular, the formulation and application of geometrical-optics approximation and its generalization. We then discuss the progress in non-linear optics, in particular, the enhancement of a first-order Freedericksz transition and intrinsic optical bistability in homeotropic and parallel oriented nematic liquid crystal cells. Finally, we discuss the liquid crystal alignment and surface effects on field-induced Freedericksz transition. 50 refs.

We have measured directed transverse momentum and multi-fragment emission for the systems of 35 MeV/nucleon 40Ar-51V, 50 MeV/nucleon 12C + 12C, and 50, 70, and 130 MeV/nucleon 139La + 139La. We observe that directed transverse momentum increases with decreasing mass of the system at energies around 50 MeV/nucleon. In addition the directed transverse momentum goes to 0 as the beam energy is decreased from 130 to 50 MeV/nucleon for La + La. We present results for multiparticle emission from the same systems in terms of global momentum space variables. We demonstrate that there are observable differences between sequential and simultaneous emission dynamics using global variables. Our results for 35 MeV/nucleon Ar + V fall closer to the sequential simulations than the simultaneous.

In partnership with the NREL/DOE PV Manufacturing R&D Program, Energy Conversion Devices, Inc. (ECD) has developed a comprehensive set of online diagnostic systems that allow real-time measurement of PV device characteristics in-situ during amorphous silicon (a-Si) deposition, prior to deposition of ITO, PV device characteristics measured include open-circuit voltage (V/sub oc/), charging rate (CR), and thickness (t) of each of the three cells in the triple-junction device. Measurements are made with an rms precision of about 0.05%, and at periods of 1 s to 1 min (1 cm to 1 m). The information from these systems is displayed real-time in the control room for online quality assurance (QA) and trouble-shooting. The diagnostics systems have been incorporated into software feedback loops to control film thicknesses. We are now beginning the development of programs for continuous online optimization.

Magnetic measurements have been performed on the prototype dipole for the high power IR-FEL presently under construction at the Thomas Jefferson National Accelerator Facility. The optics-driven requirements for these magnets include low fields, large horizontal apertures, tight field homogeneity, absolute setability of core field and integrated field, and control of the horizontal & vertical focusing terms designed into the magnets. A prototype dipole was fabricated and underwent several iterations of mechanical adjustment and magnetic measurement. Measurements were made to quantify the effects of field clamps on vertical focusing terms and effective length. Additional tests were made using various applications of Purcell gaps and high permeability materials in order to achieve the required homogeneity. Results from the prototype have been integrated into the design of the seven families of dipoles needed for the FEL.

The development of beam-based digital feedback systems for the CEBAF accelerator has gone through several stages. As the accelerator moved from commissioning to operation for the nuclear physics program, the top priority was to stabilize the beam against slow energy and position drifts (

An EPICS-based control interface has been developed which enables effective monitoring of the 338 independent RF systems that drive CEBAF's superconducting cavities. Visual screens allow the operator to quickly identify cavities that have faulted, or which are operating out of specification. These screens allow the operator easy access to automated routines for clearing faults, routines for documenting and tracking hardware problems, and expert screens for immediate correction of RF problems. The combination of visual screens and automated scripts has greatly decreased the time required to identify and recover from RF problems, significantly increasing operational uptime.

Solar neutrinos from the decay of 8B have been detected at the Sudbury Neutrino Observatory (SNO) via the charged current (CC) reaction on deuterium and by the elastic scattering (ES) of electrons. The CC reaction is sensitive exclusively to νe, while the ES reaction also has a small sensitivity to νμ and ντ. The flux of νe from 8B decay measured by the CC reaction rate is φCC(ν e )=[1.75±0.07(stat.) −0.11 +0.12 (syst.)×0.05(theor.)]×106cm−2s−1. Assuming no flavor transformation, the flux inferred from the ES reaction rate is φES(ν x )=[2.39±0.34(stat.) −0.14 +0.16 (syst.)]×106cm−2s−1. Comparison of φCC(νe) to the Super-Kamiokande collaboration’s precision value of φES(νx) yields a 3.3σ difference, assuming the systematic uncertainties are normally distributed, providing evidence that there is a nonelectron flavor active neutrino component in the solar flux. The total flux of active 8B neutrinos is thus determined to be (5.44±0.99)×106 cm−2 s−1, in close agreement with the predictions of solar models.

This paper presents interim conceptual plans for upgrading the Continuous Electron Beam Accelerator Facility (CEBAF) at the Thomas Jefferson National Accelerator Facility to extend Jefferson Lab's world leadership in nuclear physics research. The CEBAF accelerator was designed in the mid-1980's to provide beams of electrons at an energy of 4 GeV (billion electron volts) for use as probes of the atom's nucleus in CEBAF's three experiment halls. As of early 1999, the accelerator exceeds its design energy by routinely operating above 5.5 GeV. When upgraded, it will provide 11 GeV electron beams for studies in existing experimental halls and 12 GeV electrons to generate photon beams for related but qualitatively different nuclear studies in a new Hall D.

The structural and accessory proteins of human immunodeficiency virus type 1 are expressed by unspliced or partially spliced mRNAs. Efficient transport of these mRNAs from the nucleus requires the binding of the viral nuclear transport protein Rev to an RNA stem-loop structure called the RRE (Rev response element). However, the RRE does not permit Rev to stimulate the export of unspliced mRNAs from the efficiently spliced beta-globin gene in the absence of additional cis-acting RNA regulatory signals. The p17gag gene instability (INS) element contains RNA elements that can complement Rev activity. In the presence of the INS element and the RRE, Rev permits up to 30 % of the total beta-globin mRNA to be exported to the cytoplasm as unspliced mRNA. Here, we show that a minimal sequence of 30 nt derived from the 5' end of the p17 gag gene INS element (5' INS) is functional and permits the export to the cytoplasm of 14% of the total beta-globin mRNA as unspliced pre-mRNA. Gel mobility shift assays and UV cross-linking experiments have shown that heterogeneous nuclear ribonucleoprotein (hnRNP) A1 and a cellular RNA-binding protein of 50 kDa form a complex on the 5' INS. Mutants in the 5' INS that prevent hnRNP A1 and 50 kDa protein binding are inactive in the transport assay. To confirm that the hnRNP A1 complex is responsible for INS activity, a synthetic high-affinity binding site for hnRNP A1 was also analysed. When the high affinity hnRNP A1 binding site was inserted into the beta-globin reporter, Rev was able to increase the cytoplasmic levels of unspliced mRNAs to 14%. In contrast, the mutant hnRNP A1 binding site, or binding sites for hnRNP C and L are unable to stimulate Rev-mediated RNA transport. We conclude that hnRNP A1 is able to direct unspliced globin pre-mRNA into a nuclear compartment where it is recognised by Rev and then transported to the cytoplasm.

A family of large bending dipoles has been successfully magnetically measured, installed and is operational in the high power IR-FEL. These magnets are unique in that they bend the beam 180 degrees on a 1 meter radius. The optics requirements for the magnets include low fields, large horizontal apertures, tight field homogeneity, high repeatability of core field and integrated field, and control of the horizontal and vertical focusing terms that are designed into the magnets. Quantifying the optics requirements proved to be a difficult task, due to the magnet's mechanical construction and sharp bending radius. The process involved in measuring and achieving the results are discussed.

The CEBAF accelerator at the Thomas Jefferson National Accelerator Facility contains 415 resistive dipoles in the recirculation arcs and transport lines. These dipoles were originally designed and magnetically mapped to support the operation of the accelerator at 6 GeV. Recent interests in upgrading the CEBAF energy beyond 6 GeV prompted a study into operating the dipoles beyond their design limits. Finite element modeling was performed to quantify saturation effects at higher currents and to test simple modifications to improve magnetic performance. For confirmation, various setups were prototyped and magnetically measured. Measurement results agreed with finite element models and showed that saturation could be reduced to manageable levels. It was found that the most populous dipole families could be modified to reach twice their design field with minimal cost and effort. At these higher fields, the magnets operate at a reasonable thermal state with minimal saturation losses and little degradation in field quality. Work continues on studying the smaller populations of dipoles to determine their performance at higher fields.

The CEBAF accelerator at Thomas Jefferson National Accelerator Facility (Jefferson Lab) successfully began its experimental nuclear physics program in November of 1995 and has since surpassed predicted machine availability. Part of this success can be attributed to using the EPICS (Experimental Physics and Industrial Control System) control system toolkit. The CEBAF control system is one of the largest accelerator control system now operating. It controls approximately 338 SRF cavities, 2,300 magnets, 500 beam position monitors and other accelerator devices, such as gun hardware and other beam monitoring devices. All told, the system must be able to access over 125,000 database records. The system has been well received by both operators and the hardware designers. The EPICS utilities have made the task of troubleshooting systems easier. The graphical and test-based creation tools have allowed operators to custom build control screens. In addition, the ability to integrate EPICS with other software packages, such as Tcl/Tk, has allowed physicists to quickly prototype high-level application programs, and to provide GUI front ends for command line driven tools. Specific examples of the control system applications are presented in the areas of energy and orbit control, cavity tuning and accelerator tune up diagnostics.

The complete biologically active human immunodeficiency virus type-1 (HIV-1) rev-response element (RRE) RNA is 351 nucleotides (nt) in length, and includes an extra 58 nt on the 5' end and 59 nt on the 3' end beyond the sites proposed in the original models for the RRE secondary structure. The extra sequences are able to form a duplex structure which extends Stem I. The presence of an elongated Stem I structure in the RRE RNA was confirmed by nuclease mapping experiments. Nuclease protection experiments have shown that rev binds to restricted regions of the RRE, including the high affinity site located at the base of Stem IIb and along the length of the Stem I region. The three large stem-loop structures which protrude from Stem I and Stem IIb (Stems IIc, III+IV and V) remain accessible to nucleases even in the presence of a large excess of protein. Gel-retardation experiments show that the truncations of Stem I reduced the total number of rev molecules that can bind co-operatively and with high affinity to the RRE RNA. To test whether the elongated Stem I structure is required for maximal rev activity, a series of truncations which progressively reduced the length of Stem I was introduced into an HIV-1 derived reporter plasmid. In the presence of rev and a functional RRE, there is an increase in the levels of gag and env mRNA in the cytoplasm and a decrease in levels of tat and rev mRNAs. Each of the truncations in Stem I reduced the rev responses, with the longest truncations producing the greatest losses of activity. The data suggest that the RRE acts as a "molecular rheostat" designed to detect rev levels during the early stages of the HIV growth cycle.

Synthetic oligoribonucleotides have been prepared and annealed to form model RNA duplexes that mimic the high affinity RNA recognition sites for the HIV-1 tat and rev proteins. The contributions of individual functional groups on the model RNAs to the specificity of binding by their respective proteins were studied by use of oligoribonucleotides containing site-specifically modified nucleotides. Both tat and rev appear to recognise specifically a limited number of functional groups in the major groove of an RNA double helix distorted by virtue of unpaired or non-Watson-Crick paired nucleotides.

By studying light charged particles emitted in coincidence with projectile-like fragments, we probe heavy ion reaction mechanisms that result in the production of light particles in peripheral collisions. Triple coincidence {alpha}-{alpha}-{sup 12}C correlations in the reactions of 35 MeV/nucleon {sup 16}O with Ni conclusively identify previously known sources of light particles. The fast, beam velocity component of {alpha} particles in coincidence with projectile-like fragments is associated with the breakup of the projectile. The correlations suggest that the origin of the intermediate velocity component of {alpha} particles is the target nucleus. Both of these components are characterized by {alpha} particles emitted during the early stages of the collision.

Light charged fragments from the reaction {sup 40}Ar+{sup 51}V at 35--85 MeV/nucleon in 10 MeV/nucleon steps have been measured with a 4{pi} detector. The observed transverse collective momentum in central collisions decreases monotonically from 45 to 85 MeV/nucleon. The data are interpreted assuming that the attractive mean-field deflects the fragments to negative scattering angles. As the beam energy is raised, the attractive scattering is opposed by the buildup of compressed nuclear matter. A lower limit of 76 MeV/nucleon is placed on the beam energy where the attractive deflection is balanced by the repulsive side-splash mechanism. The results are compared to theoretical predictions and it is demonstrated the predictions are sensitive to two aspects of nuclear matter physics: the in-medium nucleon-nucleon cross section and the nuclear compressibility.

Azimuthal distributions of fragments with respect to the reaction plane are studied in the Ar+V system as a function of beam energy. Light charged particles are found to exhibit an enhanced emission in the reaction plane which increases with the mass of the detected particle. As the beam energy is increased, the asymmetry decreases. Possible mechanisms behind the asymmetry, such as rotational collective motion and directed transverse momentum, are discussed.

It is experimentally demonstrated that an applied dc magnetic field can transform the optical Fr\'eedericksz transition in a nematic film from second order to first order. The results are in good agreement with theoretical predictions.

We examine a variety of methods for determining both the impact parameter and the direction of the impact vector in symmetric nuclear collisions at intermediate energies. Two quantities, the particle multiplicity and the midrapidity charge, retain their dependence on the impact parameter after filtering through the acceptance of a typical 4\ensuremath{\pi} detector. By gating on these quantities we can select four ranges of impact parameters. There is some overlap of these ranges. It is noted that this is dependent on the model used to simulate the collisions. The midrapidity charge has the advantage that it integrates over the final fragments and should be less sensitive to how the collision zone disassembles. The angle of the impact vector is well reproduced with the method developed by Danielewicz and Odyniec. The difference between known and determined reaction plane has a half-width at half-maximum of less than 70\ifmmode^\circ\else\textdegree\fi{}. Some comparisons are made to experimental data.