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STUDY DESIGN A case-control study of risk alleles for degenerative disc disease (DDD) using magnetic resonance (MR) imaging for phenotyping. OBJECTIVE We aim to provide the first statistically adequately powered study of the relationship between the presence of common risk alleles and occurrence of DDD in Eastern US population. SUMMARY OF BACKGROUND DATA Many genetic predisposing factors have been identified in elevating the risk of DDD, including common variants in VDR, COL1A1, AGC1, COL9A2/3 genes. METHODS We utilized the Mass General Brigham (MGB) Biobank in which subjects' Medical Record is linked with genotyped data from single-nucleotide polymorphism (SNP) arrays. Subjects with lumbosacral spine MR imaging studies were used to construct the Cases cohort; the Biobank's Controls cohort was used as the Control cohort. Odds ratios (OR) and False-discovery-rate (FDR) q values from multiple-hypotheses-testing corrections were used to assess the likelihood of DDD given occurrence of the listed DDD risk alleles. RESULTS Four-hundred-fourteen subjects (mean age = 64, range = 27 to 94) were Cases and 925 Controls (mean age = 46, range = 21-61). A systematic search has identified 25 SNPs in 18 genes in the SNP arrays. At univariate level, rs1544410 in VDR was significantly associated with DDD for male subjects (odds ratio [OR] = 0.594, P = 0.011). After adjustment for all significant variants and demographics, three predictor variables had a significant association with the outcome, age (OR = 1.130, q

The electron temperature is a vital parameter in understanding the dynamics of fusion plasmas, helping to determine basic properties of the system, stability, and fast ion lifetime. We present a method for improving the sampling rate of historical Thomson scattering data by a factor of 103 on the decommissioned beam-driven C-2U field reversed configuration device by utilizing an artificial neural network. This work details the construction of the model, including an analysis of input signals and the model hyperparameter space. The model’s performance is evaluated on both a random subset and selected ensemble of testing data and its predictions are found to agree with the Thomson measurements in both cases. Finally, the model is used to reconstruct the effect of the micro-burst instability in C-2U, which is then compared to more recent results in C-2W, showing that the effects of the micro-burst on core electron temperature have been mitigated in C-2W.

Objectives Quantify the expected rate of CT radiation dose alerts for three body regions using accepted radiation dose benchmarks and assess key determinants of alert frequency. Methods This IRB-approved retrospective cohort study evaluated consecutive CT examinations performed between July and December 2013 within an academic medical system. CTDIvol x-ray tube output metrics were compared to the body-region-specific benchmark levels, Achievable Doses (AD), Diagnostic Reference Levels (DRL), and Dose Notification Values (DNV). A logistic regression model for the simulated alerts was fit as a function of the independent predictors: scanner, body region, gender, weight, and age. Results For 17,000 exams, the proportion of events triggering alerts increased with patient weight. Significant covariates were scanner, body region, patient weight and patient age (all p Conclusion Alert frequency was significantly correlated with weight, age, body region and scanner. Controllable factors include scanner functionality and associated protocol optimization. Patient factors driving alert frequency are predominantly weight, and to a lesser degree, age. Size-agnostic fixed dose thresholds can frequently produce false positive alerts in appropriately performed exams of large patients, while missing opportunities to identify outlier scans of higher-than-expected dose in small patients.

Key Points Question What is the extent of coronary artery disease among people with well-controlled HIV and low to moderate risk of atherosclerotic cardiovascular disease (ASCVD), and how is coronary artery disease associated with traditional risk, inflammatory, and immune activation indices? Findings In this cohort study of 755 people with HIV, coronary plaque was highly prevalent. Critical stenosis was rare, but higher-risk plaque features, including vulnerable plaque and high Leaman scores, were seen in approximately one-fifth of participants; plaque indices were associated with ASCVD risk scores and, independently, indices of inflammation and immune activation. Meaning These findings suggest that people with HIV at low to moderate risk of cardiovascular disease have a significant prevalence of coronary plaque associated with inflammation and immune activation markers., This cohort study examines the prevalence of coronary artery disease (CAD) among adults with well-controlled HIV and low to moderate risk of atherosclerotic cardiovascular disease using computed tomography angiography and assessment of inflammation and immune activation biomarkers., Importance Cardiovascular disease (CVD) is increased among people with HIV (PWH), but little is known regarding the prevalence and extent of coronary artery disease (CAD) and associated biological factors in PWH with low to moderate traditional CVD risk. Objectives To determine unique factors associated with CVD in PWH and to assess CAD by coronary computed tomography angiography (CTA) and critical pathways of arterial inflammation and immune activation. Design, Setting, and Participants This cohort study among male and female PWH, aged 40 to 75 years, without known CVD, receiving stable antiretroviral therapy, and with low to moderate atherosclerotic cardiovascular disease (ASCVD) risk according to the 2013 American College of Cardiology/American Heart Association pooled cohort equation, was part of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), a large, ongoing primary prevention trial of statin therapy among PWH conducted at 31 US sites. Participants were enrolled from May 2015 to February 2018. Data analysis was conducted from May to December 2020. Exposure HIV disease. Main Outcomes and Measures The primary outcome was the prevalence and composition of CAD assessed by coronary CTA and, secondarily, the association of CAD with traditional risk indices and circulating biomarkers, including insulin, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL) 6, soluble CD14 (sCD14), sCD163, lipoprotein-associated phospholipase A2 (LpPLA2), oxidized low-density lipoprotein (oxLDL), and high-sensitivity C-reactive protein (hsCRP). Results The sample included 755 participants, with a mean (SD) age of 51 (6) years, 124 (16%) female participants, 267 (35%) Black or African American participants, 182 (24%) Latinx participants, a low median (interquartile range) ASCVD risk (4.5% [2.6%-6.8%]), and well-controlled viremia. Overall, plaque was seen in 368 participants (49%), including among 52 of 175 participants (30%) with atherosclerotic CVD (ASCVD) risk of less than 2.5%. Luminal obstruction of at least 50% was rare (25 [3%]), but vulnerable plaque and high Leaman score (ie, >5) were more frequently observed (172 of 755 [23%] and 118 of 743 [16%], respectively). Overall, 251 of 718 participants (35%) demonstrated coronary artery calcium score scores greater than 0. IL-6, LpPLA2, oxLDL, and MCP-1 levels were higher in those with plaque compared with those without (eg, median [IQR] IL-6 level, 1.71 [1.05-3.04] pg/mL vs 1.45 [0.96-2.60] pg/mL; P = .008). LpPLA2 and IL-6 levels were associated with plaque in adjusted modeling, independent of traditional risk indices and HIV parameters (eg, IL-6: adjusted odds ratio, 1.07; 95% CI, 1.02-1.12; P = .01). Conclusions and Relevance In this study of a large primary prevention cohort of individuals with well-controlled HIV and low to moderate ASCVD risk, CAD, including noncalcified, nonobstructive, and vulnerable plaque, was highly prevalent. Participants with plaque demonstrated higher levels of immune activation and arterial inflammation, independent of traditional ASCVD risk and HIV parameters.

In the current experimental device of TAE Technologies, C-2W (also called "Norman"), record breaking advanced beam-driven field-reversed configuration (FRC) plasmas are produced and sustained in steady state utilizing variable energy neutral beams (15-40 keV, total power up to 20 MW), advanced divertors, bias electrodes, and an active plasma control system. This fully operational experiment is coupled with a fully operational suite of advanced diagnostic systems. The suite consists of 60+ individual systems spanning 20 categories, including magnetic sensors, Thomson scattering, interferometry/polarimetry, spectroscopy, fast imaging, bolometry, reflectometry, charged and neutral particle analysis, fusion product detection, and electric probes. Recently, measurements of main ion temperatures via a diagnostic neutral beam, axial profiles of energy flux from an array of bolometers, and divertor and edge plasma parameters via an extensive set of electric probes, interferometers, and spectrometers have all been made available. All the diagnostics work together to provide a complete picture of the FRC, fast-ion inventory, and edge plasma details enabling tomographic reconstruction of plasma parameter profiles and real-time plasma control.

Chlorophyll-a (Chl-a) concentration is an important indicator of phytoplankton bloom and water eutrophication. It is also a basic parameter of water quality. Remote sensing technology has been widely used for water quality monitoring in the past. In this study, the Chinese GF1 (Gaofen-1) WFV (Wide Field of View) images acquired on May 19th, 2016 were used to retrieve Chl-a concentration of central Bohai sea in order to assess the recovery condition of marine ecosystem which has been seriously polluted by the Penglai 19-3 platform oil spill accident in 2011. The remote sensing model of Chl-a concentration was developed using the linear regression method. The leave-one-out cross-validation (LOOCV) method showed that the average relative error and root mean square error (RMSE) between retrieved Chl-a concentration and in situ measurement was 11.67% and 0.1808, respectively. It indicated that the remote sensing model could correctly reflect the Chl-a concentration and its spatial distribution of the study area. The average Chl-a concentration in the buffer regions with the distance of 2km, 4km, 6km to the Penglai 19-3 platform was 0.32μg/L, 0.37μg/L and 0.40μg/L, respectively. They were in normal range and lower than that of the coastal waters. The spatial distribution of the result was similar to previous studies of Bohai sea in spring. These results indicated that Chl-a concentration of central Bohai sea was returned to normal after oil spill accident occurred for 5 years. The growth of phytoplankton in surface seawater has been returned to normal. The major causes for Chl-a concentration in the Bohai Sea was the land-sourced pollutant during the study period.

C-2 is a unique, large compact-toroid (CT) device at Tri Alpha Energy that produces field-reversed configuration (FRC) plasmas by colliding and merging oppositely directed CTs. Significant progress has recently been made on C-2, achieving ~5 ms stable plasmas with a dramatic improvement in confinement, far beyond the prediction from the conventional FRC scaling. This stable, long-lived FRC plasma state is called the high-performance FRC (HPF) regime. The key approaches to achieve the HPF regime are as follows: (i) dynamic FRC formation by collision/merging of super-Alfvenic CTs, (ii) effective control of stability and transport by end-on plasma guns and neutral-beam (NB) injection, and (iii) active wall conditioning using titanium and lithium gettering systems. Moreover, further improvement in FRC confinement has been obtained with improved open-field-line plasma properties such as a lower fluctuation level, reduced transport rates in radial/axial directions, and lower background neutral density a...

TAE Technologies' research is devoted to producing high temperature, stable, long-lived field-reversed configuration (FRC) plasmas by neutral-beam injection (NBI) and edge biasing/control. The newly constructed C-2W experimental device (also called "Norman") is the world's largest compact-toroid (CT) device, which has several key upgrades from the preceding C-2U device such as higher input power and longer pulse duration of the NBI system as well as installation of inner divertors with upgraded electrode biasing systems. Initial C-2W experiments have successfully demonstrated a robust FRC formation and its translation into the confinement vessel through the newly installed inner divertor with adequate guide magnetic field. They also produced dramatically improved initial FRC states with higher plasma temperatures (Te ~250+ eV; total electron and ion temperature g1.5 keV, based on pressure balance) and more trapped flux (up to ~15 mWb, based on rigid-rotor model) inside the FRC immediately after the merger of collided two CTs in the confinement section. As for effective edge control on FRC stabilization, a number of edge biasing schemes have been tried via open field-lines, in which concentric electrodes located in both inner and outer divertors as well as end-on plasma guns are electrically biased independently. As a result of effective outer-divertor electrode biasing alone, FRC plasma diamagnetism duration has reached up to ~9 ms which is equivalent to C-2U plasma duration. Magnetic field flaring/expansion in both inner and outer divertors plays an important role in creating a thermal insulation on open field-lines to reduce a loss rate of electrons, which leads to improvement of the edge and core FRC confinement properties. Experimental campaign with inner-divertor magnetic-field flaring has just commenced and early result indicates that electron temperature of the merged FRC stays relatively high and increases for a short period of time, presumably by NBI and ExB heating.

Department of Physics and Astronomy, UCLA, Los Angeles, CA 90095, USAA high temperature, stable, long-lived field-reversed configuration (FRC) plasma state has been produced in the C-2 device by dynamically colliding and merging two oppositely directed compact toroids, with combining effects of biasing edge plasma near the FRC separatrix from an end-plasma-gun with magnetic-mirror-plugs andof neutral-beam (NB) injection. The plasma-gun creates an inward radial electric field which mitigates the n = 2rotational instability. The gun also produces E×B velocity shear in the FRC edge layer, which may explain observations of improved transport properties. The FRCs are nearly axisymmetric which enables fast ion confinement, and increasing NB power input clearly extends the FRC lifetime. The combined effects of the plasma-gun with mirror-plugs and of NB injection yield anew High Performance FRC regime with confinement times improved by factors 2 to 4 and FRC lifetimes extended from 1 to 3 ms.

The C-2/C-2U Thomson scattering system has been substantially upgraded during the latter phase of C-2/C-2U program. A Rayleigh channel has been added to each of the three polychromators of the C-2/C-2U Thomson scattering system. Onsite spectral calibration has been applied to avoid the issue of different channel responses at different spots on the photomultiplier tube surface. With the added Rayleigh channel, the absolute intensity response of the system is calibrated with Rayleigh scattering in argon gas from 0.1 to 4 Torr, where the Rayleigh scattering signal is comparable to the Thomson scattering signal at electron densities from 1 × 1013 to 4 × 1014 cm−3. A new signal processing algorithm, using a maximum likelihood method and including detailed analysis of different noise contributions within the system, has been developed to obtain electron temperature and density profiles. The system setup, spectral and intensity calibration procedure and its outcome, data analysis, and the results of electron tem...

Conventional field-reversed configurations (FRC) face notable stability and confinement concerns, which can be ameliorated by introducing and maintaining a significant fast ion population in the system. This is the conjecture first introduced by Norman Rostoker multiple decades ago and adopted as the central design tenet in Tri Alpha Energy’s advanced beam driven FRC concept. In fact, studying the physics of such neutral beam (NB) driven FRCs over the past decade, considerable improvements were made in confinement and stability. Next to NB injection, the addition of axially streaming plasma guns, magnetic end plugs, as well as advanced surface conditioning lead to dramatic reductions in turbulence driven losses and greatly improved stability. In turn, fast ion confinement improved significantly and allowed for the build-up of a dominant fast particle population. This recently led to the breakthrough of sustaining an advanced beam driven FRC, thereby demonstrating successful maintenance of trapped magnetic flux, plasma dimensions and total pressure inventory for times much longer than all characteristic system time scales and only limited by hardware and electric supply constraints.

In modern field-reversed configuration (FRC) experiments (Binderbauer et al 2015 Phys. Plasmas 22 056110) at TAE Technologies, classical FRC instabilities are suppressed by advanced neutral beam injection and edge biasing methods, leading to high plasma confinement and fast ion pressure built-up which is comparable to the bulk plasma pressure. In some of these high performance FRC plasmas, a new macroscopically non-destructive fast ion driven micro-burst instability is observed as periodic small amplitude bursts with frequency down chirping in the diamagnetic drift frequency range, repeating about every 0.1 to 0.5 ms. The occurrence of these micro-bursts and burst-free operation can be controlled by changing the injected neutral beam energy. Major observed characteristics of this new instability are presented. Possible explanation of the phenomenon is suggested.

TAE Technologies' newly constructed C-2W experiment aims to improve the ion and electron temperatures in a sustained field-reversed configuration plasma. A suite of Thomson scattering systems has been designed and constructed for electron temperature and density profile measurements. The systems are designed for electron densities of 1 × 1012 cm-3 to 2 × 1014 cm-3 and temperature ranges from 10 eV to 2 keV. The central system will provide profile measurements of Te and ne at 16 radial locations from r = -9 cm to r = 64 cm with a temporal resolution of 20 kHz for 4 pulses or 1 kHz for 30 pulses. The jet system will provide profile measurements of Te and ne at 5 radial locations in the open field region from r = -5 cm to r = 15 cm with a temporal resolution of 100 Hz. The central system and its components have been characterized, calibrated, installed, and commissioned. A maximum-likelihood algorithm has been applied for data processing and analysis.

The new C-2W Thomson scattering (TS) diagnostic consists of two individual subsystems for monitoring electron temperature (Te) and density (ne): one system in the central region is currently operational, and the second system is being commissioned to monitor the open field line region. Validating the performance of the TS's custom designed system components and unique calibration of the detection system and diagnostic as a whole is crucial to obtaining high precision Te and ne profiles of C-2W's plasma. The major components include a diode-pumped Nd:YAG laser which produces 35 pulses at up to 20 kHz, uniquely designed collection lenses with a fast numerical aperture, and uniquely designed polychromators with filters sets to optimize a Te ranging from 10 eV to 2 keV. This paper describes the design principles and techniques used to characterize the main components of the TS diagnostic on C-2W, as well as the results of Rayleigh scattering calibrations performed for the whole system response.

A Charge Exchange Recombination Spectroscopy (ChERS) system has been used to measure the velocity, density, and temperature profiles of fully stripped carbon impurities in the Helically Symmetric eXperiment (HSX). Velocity measurements have been obtained by reversing the magnetic field between sets of shots in order to reverse the plasma flow velocity. This essentially doubles the Doppler shift of the measured photons. It also eliminates the need to accurately determine the exact wavelength of the unshifted emission line which can depend on plasma conditions. Because two viewing angles are used for each radial location, the velocity magnitude and direction can be determined. The intrinsic velocity is found to move primarily in the direction of quasihelical symmetry with a peak velocity ∼20 km/s. The velocity increases with increasing ECRH power (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Estuaries are elementary geochemical fronts where river water and seawater mix. Within this mixing zone, iron and other non-conservative elements can undergo complex reactions to form new solid phases. In order to understand authigenic iron oxide formation in the Yangtze River Estuary, two onsite water-mixing sets of experiments were conducted, one by mixing variable amounts of unfiltered Yangtze River water with filtered East China Sea water of different salinity (set 1), the other by mixing variable amounts of filtered Yangtze River water with filtered East China Sea water of different salinity (set 2). In set 2, the minerals newly formed in the course of mixing were investigated by means of a scanning electron microscope fitted with an energy-dispersive X-ray analytical system. It was found that ferrihydrite and lepidocrocite were formed in these mixing experiments, coexisting in nearly equal amounts. These iron oxides appear as aggregated particles with a large grain-size range of several microns to more than 100 μm. The electrolytic properties of seawater played an important role in the formation of these authigenic iron oxides. Kaolinite and organic aggregates were also found in the experimentally mixed pre-filtered waters. Amounts of newly formed suspended matter (set 2) were one to three orders of magnitude lower than those of total suspended matter (TSM) (set 1). This implies that newly formed minerals represent only a very small proportion of TSM in the estuarine mixing zone of the Yangtze River.

Toxoplasma gondii is an obligate intracellular parasite that has a remarkable ability to infect almost all warm-blooded animals, including humans. This study was aimed to determine the genetic characteristics of T. gondii isolates from domestic animals in Henan Province, central China. A total of 363 DNA samples, including 208 from hilar lymph nodes of pigs, 36 from blood samples of cats, 12 from tissues of aborted bovine fetuses and 107 from blood samples of dams with history of abortion in Henan Province, were examined for the presence of T. gondii by nested PCR based on B1 gene. The positive DNA samples were further genotyped by PCR-RFLP at 11 markers, including SAG1, (3'+ 5') SAG2, alt.SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico. DNA samples from 9 pigs, 5 cats, and 4 dairy cows were T. gondii B1 gene positive. Nine samples were successfully genotyped at all genetic loci, of which 5 samples from pigs, and 2 from cats were identified as ToxoDB genotype #9, and 2 samples from cows belonged to ToxoDB genotype #225. To our knowledge, the present study is the second report of genetic typing of T. gondii isolates from cattle in China, and the first report of T. gondii ToxoDB#225 from cattle.

Recent results are summarized for the Helically Symmetric Experiment (HSX), which has the capability of running as a quasi-helically symmetric stellarator or as a more conventional, nonsymmetric stellarator. From X-ray measurements, we have demonstrated improved confinement of energetic particles. With central electron cyclotron heating, the density profiles in the quasi-symmetric configuration are peaked, in contrast to the hollow or flat profiles when the symmetry is broken. The difference in profiles is attributed to the lowering of the neoclassical thermodiffusive flux when the symmetry is present. The central electron temperature is ∼200 eV higher for the quasi-symmetric configuration over the nonsymmetric case. The power deposition profiles are similar for the two cases, implying that the neoclassical electron thermal conductivity is reduced with quasi-symmetry. Related to the good confinement characteristics in the quasi-symmetric mode of operation, fluctuations in the density and magnetic field, consistent with that of a global Alfven eigenmode (GAE), are observed. While the neoclassical characteristics of the quasi-symmetric and nonsymmetric configurations are very different, we have yet to find, under present operating conditions, any significant difference (other than the possible GAE mode) in turbulence characteristics or blob formation at the plasma edge.

Thomson scattering and diamagnetic loop measurements in a hot electron plasma in the Helically Symmetric Experiment (HSX) indicate that the central electron temperature and stored energy increase linearly with power. Experimentally it is found that the central electron temperature is roughly independent of plasma density. The ASTRA code is used to model electron cyclotron heating for a magnetic configuration that is quasi-symmetric as well as for a configuration in which the symmetry is broken. The experimental results are consistent with an anomalous thermal conductivity that scales inversely with the density. However, the experimental scaling of the stored energy against density is not usually in agreement with the model. From the measured X-ray flux and the high absorbed power, as well as from the calculated low single-pass absorption efficiency, it is concluded that at low densities, a nonthermal electron population accounts for a significant fraction of the stored energy. With the ASTRA code, it is also possible to model under what conditions the central electron temperature in the quasi-symmetric configuration will be measurably greater than the temperature in the nonsymmetric configuration. These calculations depend greatly on the radial electric field of the nonsymmetric plasma but suggest that at somewhat higher densitymore » and higher power than achieved to date, differences in the central electron temperature may be observed.« less

The frequency dependence of the tokamak plasma response to the externally applied rotating helical field was investigated by measuring the radial profile of the perturbation field with small magnetic probes which were inserted in the plasma. The experimental results are discussed, directly comparing with the generally accepted linear theory, and taking into account the E×B drift and diamagnetic effect of the plasma. It was found that the experimental results are in good agreement with the simple linear analysis based on the single helicity approximation in a cylindrical geometry, except for the ergodic region, which comes from the overlapping of several sideband components of the perturbation. It is also found that the radial component of the perturbation field is still amplified inside the resonance surface (r

A detailed experimental investigation of plasma fluctuation and its modification due to radial electric field effects, both its shear and curvature, has been carried out on the Current Sustained Torus IV at Nagoya University [Takamura et al., J. Plasma Fusion Res. 74, 38 (1998)] through measurement with an array of Langmuir probes. The observed statistical dispersion relation indicates a drift-wave-type turbulence. An examination of the radial electric field shear and curvature effects on the fluctuations as well as comparisons to theoretical predictions are presented. The decorrelation of turbulence is found to be influenced by the radial electric field shear in our experiment. A modification of the poloidal correlation length and the two-poloidal-point coherency due to the radial electric field has also been identified. Nonlinear analysis of quadratic mode coupling indicates that the radial electric field can affect the fluctuation amplitudes by modifying the coupling between different spectral componen...

A high performance liquid chromatography method was established for simultaneously determining four bioactive components, salicin, liquiritin, paeonolum, and imperatorin in Fengshiding capsule, a widely used traditional Chinese medicine for treating rheumatic disease. The chromatographic separation was performed on a Shimadzu Shim-pack Stable Bond C18 column using gradient elution with methanol and water. The analytical method was validated through precision, repeatability and stability, and the relative standard deviation values were less than 3%, respectively. The recoveries of the four investigated compounds ranged from 95.80 to 101.21% with relative standard deviation values less than 3.2%. Then this proposed method was successfully applied to determine six batches of Fengshiding commercial products of capsule dosage form from two pharmaceutical factories. This study might provide a basis for quality control for this traditional Chinese medicine preparation.

We report the design and the performance of the ten-point Thomson scattering system installed on Helical Symmetry Experiment (HSX). Based upon the design of the GA Thomson scattering system, the HSX Thomson scattering system covers the complete plasma cross section, providing a ten-point plasma parameter profile measurement during a single plasma shot. The system consists of a commercial 1 J–10 ns yttrium–aluminum–garnet laser, ten polychromators from GA, the specially designed collection optics, a CAMAC data acquisition unit, and a controlling computer. The high throughput collection optics enables measurement even at a plasma density of 0.5×1012 cm−3. The system configuration, spectral response calibration, Raman calibration of the system, and operational results are presented.

During an immune response, activated B cells undergo isotype switching and begin to express isotypes other than IgM and IgD. Isotype switching occurs when downstream C gamma, C alpha, or C epsilon genes are rearranged into the S mu chromosomal region, resulting in the deletion of the region in between. These rearrangements usually occur in cis, i.e., intrachromosomally. In previous studies, we analyzed allotypic specificities of rabbit secretory IgA and identified a substantial number of IgA heavy chains with VH and C alpha allotypes that were encoded by VH and C alpha genes in trans. In those studies, however, we could not determine whether the trans association of VH and C alpha occurred during VDJ gene rearrangement or during isotype switching. Here, we cloned rabbit cDNA which encodes these trans IgA heavy chains and determined the chromosomal origin of the VH, JH, and C alpha regions. To determine whether the trans association occurred during VDJ gene rearrangement, we analyzed the nucleotide polymorphism of the JH region and the VH allotype encoded by the cDNA. We found that the VH and JH genes used in the VDJ gene rearrangements were from the same chromosome, indicating that the VH, D, and JH gene rearrangements occurred in cis. Furthermore, we analyzed the DNA polymorphisms of JH and C alpha and showed that the VDJ and C alpha genes encoding the trans IgA molecules were derived from different parental chromosomes. We suggest that the trans association occurred during isotype switching. This study shows that VH and CH can associate transchromosomally as part of a normal immune response.

A significant improvement of field reversed configuration (FRC) lifetime and plasma confinement times in the C-2 plasma, called High Performance FRC regime, has been observed with neutral beam injection (NBI), improved edge stability, and better wall conditioning [Binderbauer et al., Phys. Plasmas 22, 056110 (2015)]. A Quasi-1D (Q1D) fluid transport code has been developed and employed to carry out transport analysis of such C-2 plasma conditions. The Q1D code is coupled to a Monte-Carlo code to incorporate the effect of fast ions, due to NBI, on the background FRC plasma. Numerically, the Q1D transport behavior with enhanced transport coefficients (but with otherwise classical parametric dependencies) such as 5 times classical resistive diffusion, classical thermal ion conductivity, 20 times classical electron thermal conductivity, and classical fast ion behavior fit with the experimentally measured time evolution of the excluded flux radius, line-integrated density, and electron/ion temperature. The num...

The neonatal antibody repertoire in both mouse and humans differs from that of the adult repertoire in that the neonatal repertoire uses a limited set of JH-proximal VH genes but the adult repertoires use many different VH genes. Rabbits are unusual in that adults use only three or four VH genes, with approximately 80% of the B cells using VH1, the 3'-most VH gene. To investigate whether the repertoire of neonatal rabbits differs from that of adults, we analyzed VH, D, and JH gene usage in B cells of neonatal rabbits. A total of 68 rearranged VDJ genes was cloned from mRNA and genomic DNA isolated from lymphoid tissues of newborn to 10-day-old rabbits. We found that 74% of the VDJ gene rearrangements utilized VH1 and 15% utilized the genes that we designated VHx or VHy. From the remaining VDJ genes we identified seven novel VH genes, one, VHz, which was found in mRNA. We conclude that the repertoire of utilized VH genes in neonates is limited and is similar to that of adult rabbits. We also found the D1, D2a, D2b, and JH4 gene segments preferentially rearranged. We suggest that the preferential usage of VH, D, and JH gene segments in VDJ genes is caused by preferential rearrangement rather than by selective expansion of B cells that utilize the gene segments.

In this study we investigate the molecular genetic basis for VHa- Ig. Knowing that the expression of VHa allotype Ig is suppressed by neonatal injection of rabbits with anti-VHa allotype antibody, and that the decreased level of VHa allotype Ig, VHa+, in the suppressed rabbits is compensated for by an increase in VHa- Ig, we determined the nucleotide sequences of 41 VDJ genes from a2/a2 rabbits neonatally suppressed for the expression of a2 Ig. We compared these nucleotide sequences to each other and identified two groups of VH sequences. We predict that the molecules of each group are encoded by one germline VH gene. Inasmuch as VHa+ Ig is encoded predominantly by one germline VH gene, VH1, it appears that more than 95% of the VDJ repertoire of rabbits may be encoded by as few as three germline VH genes. A genomic VDJ gene whose VH sequence was similar to those of group I molecules was expressed in vitro and was shown by ELISA to encode molecules of the VHa- allotype, y33. Analysis of the D regions in the VDJ gene indicated that germline D2b and D3 gene segments were preferentially used in the VDJ gene rearrangement. A comparison of sequences of D regions of the 41 VDJ gene rearrangements in 3-, 6-, and 9-wk-old rabbits to sequences of germline D gene segments showed an accumulation of mutations in the D region. Inasmuch as we have previously shown that V regions of rabbit VDJ genes are diversified, in part, by somatic gene conversion, it appears now that rabbit VDJ genes diversify by a combination of somatic mutation and somatic gene conversion.

Differences in the electron particle and thermal transport are reported between plasmas produced in a quasihelically symmetric (QHS) magnetic field and a configuration with the symmetry broken. The thermal diffusivity is reduced in the QHS configuration, resulting in higher electron temperatures than in the nonsymmetric configuration for a fixed power input. The density profile in QHS plasmas is centrally peaked, and in the nonsymmetric configuration the core density profile is hollow. The hollow profile is due to neoclassical thermodiffusion, which is reduced in the QHS configuration.

Conventional field-reversed configurations (FRCs), high-beta, prolate compact toroids embedded in poloidal magnetic fields, face notable stability and confinement concerns. These can be ameliorated by various control techniques, such as introducing a significant fast ion population. Indeed, adding neutral beam injection into the FRC over the past half-decade has contributed to striking improvements in confinement and stability. Further, the addition of electrically biased plasma guns at the ends, magnetic end plugs, and advanced surface conditioning led to dramatic reductions in turbulence-driven losses and greatly improved stability. Together, these enabled the build-up of a well-confined and dominant fast-ion population. Under such conditions, highly reproducible, macroscopically stable hot FRCs (with total plasma temperature of ∼1 keV) with record lifetimes were achieved. These accomplishments point to the prospect of advanced, beam-driven FRCs as an intriguing path toward fusion reactors. This paper reviews key results and presents context for further interpretation.

The world-greatest water conservancy project, Three Gorges Reservoir (TGR), stored water for the first time in June 2003, which provides an excellent opportunity to examine its effects on the sediment entering the Yangtze River estuary. A daily record dataset of water discharge and suspended sediment concentration (SSC) of the Yangtze River measured at Datong (the controlling hydrological gauging station into the estuary) from May 15 to July of 2003 spanning the water storage, together with a monthly record dataset of runoff, sediment load and SSC measured at Datong from 1953 to 2003, were used to examine the effects of the TGR water storage in June 2003 on the Yangtze River sediment entering the estuary. The results show that the unnaturally clearer water due to the TGR sedimentation resulted by the water storage in June 2003 brought the Yangtze River markedly decreased SSC and sediment load entering the estuary both during the TGR water storage and in the second half year of 2003. The Yangtze River water and sediment discharges into the estuary from 15 May to 15 July in 2003 spanning the TGR water storage clearly indicated three phases: (1) pre-water storage of the TGR from 15 May to 25 May, during this phase, SSC and sediment load increased with water discharge increasing; (2) water storage of the TGR from 25 May to 10 June (including the preparation phase from 25 May to 31 May), during this phase, SSC and sediment load decreased dramatically with water discharge decreasing; and (3) post-water storage of the TGR, at the beginning, SSC, sediment load and water discharge basically remained at a relatively low value until the end of June, and since then, SSC and sediment load increased gradually with water discharge increasing. In addition, the real total sediment load was reduced by 2456.07×104 t than the estimated total sediment load during the period from 27 May to 2 July in 2003.

Second harmonic extraordinary mode ECH is used in the HSX stellarator at 0.5 T to break down and heat the plasma. To measure the absorbed power a set of absolutely calibrated microwave diodes have been installed inside the machine. In the QHS and Mirror configuration, the absorption efficiency is high (about 0.9) and drops (to about 0.5) in the anti‐Mirror mode. A comparison with ray tracing predictions is made.

Rabbits generate their antibody repertoire in three stages. First, a neonatal repertoire is generated by B lymphopoiesis in fetal liver and bone marrow and is limited by preferential V(H) gene segment usage. Between 4 and 8 weeks after birth a complex primary antibody repertoire is developed by somatically diversifying the neonatal repertoire through somatic hypermutation and a somatic gene conversion-like mechanism in gut-associated lymphoid tissue (GALT). In rabbits, unlike other species, the development of the primary antibody repertoire through somatic diversification of Ig genes appears to be dependent on intestinal microbial flora. The primary antibody repertoire is subsequently modified during antigen-dependent immune responses in which VDJ genes further diversify both by somatic hypermutation and by a gene conversion-like mechanism (the secondary repertoire). During the various stages of development, the antibody repertoire is modified and shaped by selective processes. In this review, we discuss the roles of GALT, microbes, and B-cell selection in generating antibody diversity in rabbits.

Young Alicia rabbits use VHa-negative genes, VHx and VHy, in most VDJ genes, and their serum Ig is VHa negative. However, as Alicia rabbits age, VHa2 allotype Ig is produced at high levels. We investigated which VH gene segments are used in the VDJ genes of a2 Ig-secreting hybridomas and of a2 Ig+ B cells from adult Alicia rabbits. We found that 21 of the 25 VDJ genes used the a2-encoding genes, VH4 or VH7; the other four VDJ genes used four unknown VH gene segments. Because VH4 and VH7 are rarely found in VDJ genes of normal or young Alicia rabbits, we investigated the timing of rearrangement of these genes in Alicia rabbits. During fetal development, VH4 was used in 60-80% of nonproductively rearranged VDJ genes, and VHx and VHy together were used in 10-26%. These data indicate that during B lymphopoiesis VH4 is preferentially rearranged. However, the percentage of productive VHx- and VHy-utilizing VDJ genes increased from 38% at day 21 of gestation to 89% at birth (gestation day 31), whereas the percentage of VH4-utilizing VDJ genes remained at 15%. These data suggest that during fetal development, either VH4-utilizing B-lineage cells are selectively eliminated, or B cells with VHx- and VHy-utilizing VDJ genes are selectively expanded, or both. The accumulation of peripheral VH4-utilizing a2 B cells with age indicates that these B cells might be selectively expanded in the periphery. We discuss the possible selection mechanisms that regulate VH gene segment usage in rabbit B cells during lymphopoiesis and in the periphery.

During T cell-dependent immune responses in mouse and human, Ig genes diversify by somatic hypermutation within germinal centers. Rabbits, in addition to using somatic hypermutation to diversify their IgH genes, use a somatic gene conversion-like mechanism, which involves homologous recombination between upstream VH gene segments and the rearranged VDJ genes. Somatic gene conversion and somatic hypermutation occur in young rabbit gut-associated lymphoid tissue and are thought to diversify a primary Ab repertoire that is otherwise limited by preferential VH gene segment utilization. Because somatic gene conversion is rarely found within Ig genes during immune responses in mouse and human, we investigated whether gene conversion in rabbit also occurs during specific immune responses, in a location other than gut-associated lymphoid tissue. We analyzed clonally related VDJ genes from popliteal lymph node B cells responding to primary, secondary, and tertiary immunization with the hapten FITC coupled to a protein carrier. Clonally related VDJ gene sequences were derived from FITC-specific hybridomas, as well as from Ag-induced germinal centers of the popliteal lymph node. By analyzing the nature of mutations within these clonally related VDJ gene sequences, we found evidence not only of ongoing somatic hypermutation, but also of ongoing somatic gene conversion. Thus in rabbit, both somatic gene conversion and somatic hypermutation occur during the course of an immune response.

The rabbit genome has 13 different Calpha genes that are expressed at different levels in mucosal tissues. To analyze the factors involved in the differential expression of these Calpha genes, we cloned and sequenced the promoters of the Ialpha regions that control the expression of sterile mRNA. We found that all Calpha genes, including Calpha3 and Calpha8, which are not expressed, and Calpha4, which is expressed at high levels, have similar nucleotide sequences in the Ialpha region, and all contain the recognition elements for TGF-beta in the promoter. B lymphocytes from popliteal lymph nodes or Peyer's patch activated in vitro could be induced by TGF-beta to express sterile IgA transcripts of all IgA isotypes, except Calpha2, Calpha3, and Calpha8. Many single B lymphocytes transcribed sterile mRNA of more than one IgA isotype, which demonstrates that transcription of sterile mRNA alone does not regulate the IgA isotype switch. The addition of IL-2 led to the expression of transcripts of mature IgA of all isotypes, except Calpha2, Calpha3, and Calpha8. The predominantly expressed isotype in these experiments was Calpha4. With the use of an IgA4-specific mAb we found that IgA4+ plasma cells are unevenly distributed throughout the small intestine such that many of the IgA+ plasma cells in the duodenum-jejunum produced IgA4, whereas in the lower part of the ileum IgA4-producing cells were almost absent. Because the microbial flora varies throughout the intestine, we suggest that the microbial flora creates different local environments and thus affects either isotype switching or homing of IgA-expressing cells.

Intrinsic flow velocities of up to ?20?km?s?1 have been measured using charge exchange recombination spectroscopy (CHERS) in the quasi-helically symmetric HSX stellarator and are compared with the neoclassical values calculated using an updated version (Lore 2010 Measurement and Transport Modeling with Momentum Conservation of an Electron Internal Transport Barrier in HSX (Madison, WI: University of Wisconsin); Lore et al 2010 Phys. Plasmas 17 056101) of the PENTA code (Spong 2005 Phys. Plasmas. 12 056114). PENTA uses the monoenergetic transport coefficients calculated by the drift kinetic equation solver code (Hirshman et al 1986 Phys. Fluids 29 2951; van Rij and Hirshman 1989 Phys. Fluids B 1 563), but corrects for momentum conservation. In the outer half of the plasma good agreement is seen between the measured parallel flow profile and the calculated neoclassical values when momentum correction is included. The flow velocity in HSX is underpredicted by an order of magnitude when this momentum correction is not applied. The parallel flow is calculated to be approximately equal for the majority hydrogen ions and the C6+ ions used for the CHERS measurements. The pressure gradient of the protons is the primary drive of the calculated parallel flow for a significant portion of the outer half of the plasma. The values of the radial electric field calculated with and without momentum correction were similar, but both were smaller than the measured values in the outer half of the plasma. Differences between the measured and predicted radial electric field are possibly a result of uncertainty in the composition of the ion population and sensitivity of the ion flux calculation to resonances in the radial electric field.

Electron cyclotron heated plasmas in the Helically Symmetric Experiment (HSX) feature strongly peaked electron temperature profiles; central temperatures are 2.5 keV with 100 kW injected power. These measurements, coupled with neoclassical predictions of large “electron root” radial electric fields with strong radial shear, are evidence of a neoclassically driven thermal transport barrier. Neoclassical transport quantities are calculated using the PENTA code [D. A. Spong, Phys. Plasmas12, 056114 (2005)], in which momentum is conserved and parallel flow is included. Unlike a conventional stellarator, which exhibits strong flow damping in all directions on a flux surface, quasisymmetric stellarators are free to rotate in the direction of symmetry, and the effect of momentum conservation in neoclassical calculations may therefore be significant. Momentum conservation is shown to modify the neoclassical ion flux and ambipolar ion root radial electric fields in the quasisymmetric configuration. The effect is much smaller in a HSX configuration where the symmetry is spoiled. In addition to neoclassical transport, a model of trapped electron mode turbulence is used to calculate the turbulent-driven electron thermal diffusivity. Turbulenttransport quenching due to the neoclassically predicted radial electric field profile is needed in predictive transport simulations to reproduce the peaking of the measured electron temperature profile [Guttenfelder et al. , Phys. Rev. Lett.101, 215002 (2008)].

Measurements of particle and heat transport have been made in the Helically Symmetric Experiment [F. S. B. Anderson et al., Fusion Technology 27, 273 (1995)]. Experimental differences in the density and temperature profiles are reported between plasmas produced in a quasihelically symmetric (QHS) magnetic field and a configuration with the symmetry broken. The electron temperature is higher in the QHS configuration, due to a reduction in electron thermal diffusivity that is comparable to the neoclassical prediction. The density profile in plasmas with the symmetry broken is measured to be hollow, while in QHS plasmas the profile is centrally peaked. Calculations of the radial particle flux using the DEGAS code [D. Heifetz et al., J. Comput. Phys. 46, 309 (1982)] show that the hollow profile observed with the symmetry broken is due to neoclassical thermodiffusion. Thermodiffusion is reduced in the QHS configuration, resulting in a peaked density profile.

Overlapping cosmid clones of rabbit germ-line DNA containing VH, DH and JH gene segments were isolated. The map of this cluster of cosmid clones indicated that the rabbit VH and JH regions were separated by 63 kb. Hybridization of Southern blots of these cosmid clones with two different DH segment probes identified a total of six DH segments within the region between the VH and JH regions. The nucleotide sequences of the JH region and one of the DH segments have been determined. The DH segment has conserved heptamer and nonamer sequences separated by 12 and 11 bp at the 3' and 5' sides, respectively, of the coding region and hence, appears to be a functional gene. The nucleotide sequence of the JH region revealed four functional JH gene segments and one JH pseudogene. Inasmuch as the JH region had previously been linked by contiguous overlapping clones with C mu, C gamma, C epsilon, and one C alpha gene, this VH-DH-JH cluster and the clones containing the Ig H chain C region genes represent 190 kb of contiguous germ-line DNA of the Ig H chain locus.

The extraordinary wave at the second harmonic of the electron cyclotron frequency produces and heats the plasma in the helically symmetric experiment. Ray-tracing calculations predict 40% first pass absorption at a plasma density of 1.5 x 10 18 m -3 and an electron temperature of 400 eV To measure the wave absorption, a set of absolutely calibrated microwave detectors is installed along the machine. It was found that the absorption efficiency is very high (about 0.9) in the quasi-helically symmetric (QHS) and mirror configurations, and it drops to 0.6 in the anti-mirror mode. The confinement of particles in the different configurations is studied in the neutral gas breakdown experiments. With the same gas pressure and heating power, the density for the QHS configuration has a larger growth rate (10 4 s -1 ) compared with the mirror (5 x 10 3 s -1 ) and anti-mirror modes (2 x 10 3 s -1 ). A study of the stored energy versus launched power and plasma density shows that it increases linearly (up to 50 J) with power and has a maximum at a low plasma density (at about 0.4 × 10 18 m -3 ). The central electron temperature measured by Thomson scattering also rises linearly with heating power and reaches 600 eV at 100 kW of launched power.