Demonstration of reduced neoclassical energy transport in Wendelstein 7-X.

Research on magnetic confinement of high-temperature plasmas has the ultimate goal of harnessing nuclear fusion for the production of electricity. Although the tokamak1 is the leading toroidal magnetic-confinement concept, it is not without shortcomings and the fusion community has therefore also pursued alternative concepts such as the stellarator. Unlike axisymmetric tokamaks, stellarators possess a three-dimensional (3D) magnetic field geometry. The availability of this additional dimension opens up an extensive configuration space for computational optimization of both the field geometry itself and the current-carrying coils that produce it. Such an optimization was undertaken in designing Wendelstein 7-X (W7-X)2, a large helical-axis advanced stellarator (HELIAS), which began operation in 2015 at Greifswald, Germany. A major drawback of 3D magnetic field geometry, however, is that it introduces a strong temperature dependence into the stellarator's non-turbulent 'neoclassical' energy transport. Indeed, such energy losses will become prohibitive in high-temperature reactor plasmas unless a strong reduction of the geometrical factor associated with this transport can be achieved; such a reduction was therefore a principal goal of the design of W7-X. In spite of the modest heating power currently available, W7-X has already been able to achieve high-temperature plasma conditions during its 2017 and 2018 experimental campaigns, producing record values of the fusion triple product for such stellarator plasmas3,4. The triple product of plasma density, ion temperature and energy confinement time is used in fusion research as a figure of merit, as it must attain a certain threshold value before net-energy-producing operation of a reactor becomes possible1,5. Here we demonstrate that such record values provide evidence for reduced neoclassical energy transport in W7-X, as the plasma profiles that produced these results could not have been obtained in stellarators lacking a comparably high level of neoclassical optimization.

Retraction: Pressure-Induced Superconducting State of Europium Metal at Low Temperatures [Phys. Rev. Lett. 102, 197002 (2009)].

Retraction of DOI: 10.1103/PhysRevLett.102.197002.

Ascending Si diffusion into growing GaN nanowires from the SiC/Si substrate: up to the solubility limit and beyond.

We report a novel mechanism that allows the incorporation of Si into GaN nanowires up to and beyond the solubility limit. This mechanism is documented during the growth on vicinal (misoriented) SiC/Si hybrid substrates having the step bunches. Nanowires that are grown at these locations become heavily Si doped. Such high Si concentrations were verified by secondary-ion mass spectrometry. Photoluminescence data also point to very high carrier concentrations. Moreover, Raman spectroscopy together with quantum chemical modelling shows the build up of Si into Ga sites and indicates even the possibility of the formation of a Ga(Si)N solid solution. The microscopic mechanism responsible for heavy doping and even alloying is diffusion driven by the mechano-chemical effect, which allows for the extremely efficient injection of Si atoms into the nanowires from the step bunches at the vicinal SiC/Si substrates.

Radiologic Evaluation of Lower Leg, Ankle, and Foot Fracture Fixation Hardware.

Radiologists should be familiar with basic principles of fracture fixation and the normal imaging appearances of implant constructs and their complications. The surgeon's selection of external fixation, intramedullary nail fixation, open reduction and internal fixation, or some combination depends on patient factors, fracture configuration, injury to the soft tissue envelope, and surgeon experience. Complications including loss of fixation with resultant malalignment, nonunion, infection, and posttraumatic osteoarthritis present additional challenges for the surgeon as well as the radiologist. This article reviews the rationale behind fracture fixation in fractures of the lower leg, ankle, and foot. Examples of postoperative complications are also reviewed.

Pressure-Induced Superconductivity in Elemental Ytterbium Metal.

Ytterbium (Yb) metal is divalent and nonmagnetic (4f^{14} configuration). Under pressure its valence increases significantly leading to the expectation that magnetic instabilities and other highly correlated electron effects may appear before a stable trivalent state is reached (4f^{13} configuration). We carried out electrical resistivity and ac magnetic susceptibility measurements to 179 GPa over the temperature range 1.4-295 K. No evidence for magnetic order is observed. However, Yb becomes a superconductor at 86 GPa with T_{c}≃1.4 K, increasing to 4.6 K at 179 GPa. X-ray absorption spectroscopy shows that Yb remains mixed valent to at least 125 GPa, pointing to an active role of f electrons in the emergence of superconductivity in this simple, elemental solid.

Inhibition of RhoA reduces propofol-mediated growth cone collapse, axonal transport impairment, loss of synaptic connectivity, and behavioural deficits.

BACKGROUND: Exposure of the developing brain to propofol results in cognitive deficits. Recent data suggest that inhibition of neuronal apoptosis does not prevent cognitive defects, suggesting mechanisms other than neuronal apoptosis play a role in anaesthetic neurotoxicity. Proper neuronal growth during development is dependent upon growth cone morphology and axonal transport. Propofol modulates actin dynamics in developing neurones, causes RhoA-dependent depolymerisation of actin, and reduces dendritic spines and synapses. We hypothesised that RhoA inhibition prevents synaptic loss and subsequent cognitive deficits. The present study tested whether RhoA inhibition with the botulinum toxin C3 (TAT-C3) prevents propofol-induced synapse and neurite loss, and preserves cognitive function. METHODS: RhoA activation, growth cone morphology, and axonal transport were measured in neonatal rat neurones (5-7 days in vitro) exposed to propofol. Synapse counts (electron microscopy), dendritic arborisation (Golgi-Cox), and network connectivity were measured in mice (age 28 days) previously exposed to propofol at postnatal day 5-7. Memory was assessed in adult mice (age 3 months) previously exposed to propofol at postnatal day 5-7. RESULTS: Propofol increased RhoA activation, collapsed growth cones, and impaired retrograde axonal transport of quantum dot-labelled brain-derived neurotrophic factor, all of which were prevented with TAT-C3. Adult mice previously treated with propofol had decreased numbers of total hippocampal synapses and presynaptic vesicles, reduced hippocampal dendritic arborisation, and infrapyramidal mossy fibres. These mice also exhibited decreased hippocampal-dependent contextual fear memory recall. All anatomical and behavioural changes were prevented with TAT-C3 pre-treatment. CONCLUSION: Inhibition of RhoA prevents propofol-mediated hippocampal neurotoxicity and associated cognitive deficits.

Inhibition of p75 neurotrophin receptor does not rescue cognitive impairment in adulthood after isoflurane exposure in neonatal mice.

BACKGROUND: Isoflurane is widely used for anaesthesia in humans. Isoflurane exposure of rodents prior to post-natal day 7 (PND7) leads to widespread neurodegeneration in laboratory animals. Previous data from our laboratory suggest an attenuation of apoptosis with the p75 neurotrophin receptor (p75NTR) inhibitor TAT-Pep5. We hypothesized that isoflurane toxicity leads to behavioural and cognitive abnormalities and can be rescued with pre-anaesthesia administration of TAT-Pep5. METHODS: Neonatal mouse pups were pretreated with either TAT-Pep5 (25 µl, 10 µM i.p.) or a scrambled control peptide (TAT-ctrl; 25 µl, 10 µM i.p.) prior to isoflurane exposure (1.4%; 4 h) or control ( n = 15-26/group). Three to 5 months after exposure, behavioural testing and endpoint assays [brain volume (stereology) and immunoblotting] were performed. RESULTS: No significant difference was observed in open field, T-maze, balance beam or wire-hanging testing. The Barnes maze revealed a significant effect of isoflurane ( P = 0.019) in errors to find the escape tunnel during the day 5 probe trial, a finding indicative of impaired short-term spatial memory. No difference was found for brain volumes or protein expression. TAT-Pep5 treatment did not reverse the effects of isoflurane on neurocognitive behaviour. CONCLUSION: A single isoflurane exposure to early post-natal mice caused a hippocampal-dependent memory deficit that was not prevented by pre-administration of TAT-Pep5, although TAT-Pep5, an inhibitor of p75NTR, has been shown to reduce isoflurane-induced apoptosis. These findings suggest that neuronal apoptosis is not requisite for the development of cognitive deficits in the adults attendant with neonatal anaesthetic exposure.

3D superimposition and understanding temporomandibular joint arthritis.

OBJECTIVES: To investigate the 3D morphological variations in 169 temporomandibular ioint (TMJ) condyles, using novel imaging statistical modeling approaches. SETTING AND SAMPLE POPULATION: The Department of Orthodontics and Pediatric Dentistry at the University of Michigan. Cone beam CT scans were acquired from 69 subjects with long-term TMJ osteoarthritis (OA, mean age 39.1±15.7 years), 15 subjects at initial consult diagnosis of OA (mean age 44.9±14.8 years), and seven healthy controls (mean age 43±12.4 years). MATERIALS AND METHODS: 3D surface models of the condyles were constructed, and homologous correspondent points on each model were established. The statistical framework included Direction-Projection-Permutation (DiProPerm) for testing statistical significance of the differences between healthy controls and the OA groups determined by clinical and radiographic diagnoses. RESULTS: Condylar morphology in OA and healthy subjects varied widely with categorization from mild to severe bone degeneration or overgrowth. DiProPerm statistics supported a significant difference between the healthy control group and the initial diagnosis of OA group (t=6.6, empirical p-value=0.006) and between healthy and long-term diagnosis of OA group (t=7.2, empirical p-value=0). Compared with healthy controls, the average condyle in OA subjects was significantly smaller in all dimensions, except its anterior surface, even in subjects with initial diagnosis of OA. CONCLUSION: This new statistical modeling of condylar morphology allows the development of more targeted classifications of this condition than previously possible.

Survival after neoadjuvant chemotherapy with or without bevacizumab or everolimus for HER2-negative primary breast cancer (GBG 44-GeparQuinto)†.

BACKGROUND: The GeparQuinto study showed that adding bevacizumab to 24 weeks of anthracycline-taxane-based neoadjuvant chemotherapy increases pathological complete response (pCR) rates overall and specifically in patients with triple-negative breast cancer (TNBC). No difference in pCR rate was observed for adding everolimus to paclitaxel in nonearly responding patients. Here, we present disease-free (DFS) and overall survival (OS) analyses. PATIENTS AND METHODS: Patients (n = 1948) with HER2-negative tumors of a median tumor size of 4 cm were randomly assigned to neoadjuvant treatment with epirubicin/cyclophosphamide followed by docetaxel (EC-T) with or without eight infusions of bevacizumab every 3 weeks before surgery. Patients without clinical response to EC ± Bevacizumab were randomized to 12 weekly cycles paclitaxel with or without everolimus 5 mg/day. To detect a hazard ratio (HR) of 0.75 (α = 0.05, ß = 0.8) 379 events had to be observed in the bevacizumab arms. RESULTS: With a median follow-up of 3.8 years, 3-year DFS was 80.8% and 3-year OS was 89.7%. Outcome was not different for patients receiving bevacizumab (HR 1.03; P = 0.784 for DFS and HR 0.974; P = 0.842 for OS) compared with patients receiving chemotherapy alone. Patients with TNBC similarly showed no improvement in DFS (HR = 0.99; P = 0.941) and OS (HR = 1.02; P = 0.891) when treated with bevacizumab. No other predefined subgroup (HR+/HER2-; locally advanced (cT4 or cN3) or not; cT1-3 or cT4; pCR or not) showed a significant benefit. No difference in DFS (HR 0.997; P = 0.987) and OS (HR 1.11; P = 0.658) was observed for nonearly responding patients receiving paclitaxel with or without everolimus overall as well as in subgroups. CONCLUSIONS: Long-term results, in opposite to the results of pCR, do not support the neoadjuvant use of bevacizumab in addition to an anthracycline-taxane-based chemotherapy or everolimus in addition to paclitaxel for nonearly responding patients. CLINICAL TRIAL NUMBER: NCT 00567554, www.clinicaltrials.gov.

3D osteoarthritic changes in TMJ condylar morphology correlates with specific systemic and local biomarkers of disease.

OBJECTIVE: To assess 3D morphological variations and local and systemic biomarker profiles in subjects with a diagnosis of temporomandibular joint osteoarthritis (TMJ OA). DESIGN: Twenty-eight patients with long-term TMJ OA (39.9 ± 16 years), 12 patients at initial diagnosis of OA (47.4 ± 16.1 years), and 12 healthy controls (41.8 ± 12.2 years) were recruited. All patients were female and had cone beam CT scans taken. TMJ arthrocentesis and venipuncture were performed on 12 OA and 12 age-matched healthy controls. Serum and synovial fluid levels of 50 biomarkers of arthritic inflammation were quantified by protein microarrays. Shape Analysis MANCOVA tested statistical correlations between biomarker levels and variations in condylar morphology. RESULTS: Compared with healthy controls, the OA average condyle was significantly smaller in all dimensions except its anterior surface, with areas indicative of bone resorption along the articular surface, particularly in the lateral pole. Synovial fluid levels of ANG, GDF15, TIMP-1, CXCL16, MMP-3 and MMP-7 were significantly correlated with bone apposition of the condylar anterior surface. Serum levels of ENA-78, MMP-3, PAI-1, VE-Cadherin, VEGF, GM-CSF, TGFßb1, IFNγg, TNFαa, IL-1αa, and IL-6 were significantly correlated with flattening of the lateral pole. Expression levels of ANG were significantly correlated with the articular morphology in healthy controls. CONCLUSIONS: Bone resorption at the articular surface, particularly at the lateral pole was statistically significant at initial diagnosis of TMJ OA. Synovial fluid levels of ANG, GDF15, TIMP-1, CXCL16, MMP-3 and MMP-7 were correlated with bone apposition. Serum levels of ENA-78, MMP-3, PAI-1, VE-Cadherin, VEGF, GM-CSF, TGFß1, IFNγ, TNFα, IL-1α, and IL-6 were correlated with bone resorption.

Metabolomics Highlights Different Life History Strategies of White and Brown Rot Wood-Degrading Fungi.

White and brown rot fungi efficiently deconstruct lignocellulose in wood, Earth's largest pool of aboveground biotic carbon and an important natural resource. Despite its vital importance, little is known about the metabolomic signatures among fungal species and nutritional modes (rot types). In this study, we used GC-MS metabolomics in solid wood substrates (in planta) to compare brown rot fungi (Rhodonia placenta and Gloeophylum trabeum) and white rot fungi (Trametes versicolor and Pleurotus ostreatus) at two decay stages (earlier and later), finding identifiable patterns for brown rot fungi at later decay stages. These patterns occurred in highly reducing environments that were not observed in white rot fungi. Metabolomes measured among the two white rot fungi were notably different, but we found a potential biomarker compound, galactitol, that was characteristic to white rot taxa. In addition, we found that white rot fungi were more efficient at catabolizing phenolic compounds that were originally present in wood. Collectively, white rot fungi were characterized by measured sugar release relative to higher carbohydrate solubilization by brown rot fungi, a distinction in soluble sugar availability that might shape success in the face of "cheater" competitors. This need to protect excess free sugars may explain the differentially high brown rot fungal production of pyranones and furanones, likely linked to an expansion of polyketide synthase genes. IMPORTANCE Despite the ecological and economic importance of wood-degrading fungi, little is known about the array of metabolites that fungi produce during wood decomposition. This study provides an in-depth insight into the wood decomposition process by analyzing and comparing the changes of >100 compounds produced by fungi with metabolic distinct nutritional modes (white and brown rot fungi) at different decay stages. We found a unique pattern of metabolites that correlated well with brown rot (carbohydrate selective mode) in later decay. These compounds were in line with some of the physiochemical and genetic features previously seen in these fungi such as a faster sugar release, lower pH, and the expansion of polyketide-synthase genes compared to white rot fungi (lignin-degrading mode). This study provides spatiotemporally resolved mechanism insights as well as critical groundwork that will be valuable for studies in basic biology and ecology, as well as applied biomass deconstruction and bioremediation.

Structural correlates of cross-reactive and individual idiotypic determinants on murine antibodies to alpha-(1 leads to 3) dextran.

For the first time V-region amino acid sequence differences have been correlated with the expression of cross-reactive and individual idiotypes through an analysis of 12 dextran-binding proteins. This correlation has been possible because of the apparent sequence identity of the corresponding lambda chains. Expression of a cross-reactive idiotype was localized to two residues and/or a carbohydrate in the second hypervariable region of the heavy chain. Two individual idiotypes correlate with the two amino acids within the third hypervariable region that comprises the D segment of the dextran-binding proteins. These results demonstrate that idiotype reagents can recognize two amino acid differences within V and D segments of classical variable regions. In anti-dextran antibodies, cross-reactive idiotypes involve V-region determinants, whereas individual idiotype determinants correlate with D-segment variation.

Combining site specificities of mouse hybridoma antibodies to dextran B1355S.

The combining sites of 12 mouse hybridoma antibodies to dextran B1355S have been characterized by quantitative precipitin assay. All antibodies preferentially bind the immunizing antigen B1355S and two other class I dextrans, B1498S and B1501S, but show substantial differences in the extents to which they cross react with class I dextrans, suggesting their clustering into five groups. Three myeloma proteins, CAL20 TEPC1035, J558, and MOPC104E, which bind dextran B1355S, each fall into a different group. There appears to be a substantial, but imperfect, correlation of DH region structure and individual idiotypic determinants with dextran binding patterns. Proteins with RY DH segments and IdI (J558) idiotypes are in groups 1 or 3, and proteins with YD DH segments and IdI (MOPC104E) idiotypes are exclusively in group 5. However, identical patterns of precipitin curves accompany very different sequences in CDR3. Antibodies of group 1, which react only with class II dextrans, differ the most in primary sequence, a finding suggesting that subsites responsible for cross reactivity with class I dextrans may be blocked and that this may be effected by side chains of different amino acids. This finding delineates a new aspect of the relationship of variability in amino acid sequence to antibody complementarity.

Spontaneous symmetry breaking by charge stripes in the high pressure phase of superconducting La1.875Ba0.125CuO4.

In those cases where charge-stripe order has been observed in cuprates, the crystal structure is such that the average rotational symmetry of the CuO2 planes is reduced from fourfold to twofold. As a result, one could argue that the reduced lattice symmetry is essential to the existence of stripe order. We use pressure to restore the average fourfold symmetry in a single crystal of La1.875Ba0.125CuO4, and show by x-ray diffraction that charge-stripe order still occurs. Thus, electronically driven stripe order can spontaneously break the lattice symmetry.

Enhancement of the critical temperature of HgBa2CuO(4+δ) by applying uniaxial and hydrostatic pressure: implications for a universal trend in cuprate superconductors.

It is well known that the superconducting transition temperature (T(c)) of cuprate superconductors can be enhanced by varying certain structural and electronic parameters, such as the flatness of the CuO2 planes or their doping level. We determine the uniaxial and hydrostatic pressure derivatives of T(c) in the structurally simple tetragonal compound HgBa2CuO(4+δ) near optimal doping. Our results provide experimental evidence for two further methods to enhance T(c): (i) reducing the area of the CuO2 planes, and (ii) increasing the separation of the CuO2 planar groups. T(c) is found to couple much more strongly to the ratio c/a of the lattice constants than to the unit cell volume. A comparison with prior results for structurally more complicated cuprates reveals a general trend of uniaxial pressure derivatives with T(c).

Cellular redistribution of protein tyrosine phosphatases LAR and PTPsigma by inducible proteolytic processing.

Most receptor-like protein tyrosine phosphatases (PTPases) display a high degree of homology with cell adhesion molecules in their extracellular domains. We studied the functional significance of processing for the receptor-like PTPases LAR and PTPsigma. PTPsigma biosynthesis and intracellular processing resembled that of the related PTPase LAR and was expressed on the cell surface as a two-subunit complex. Both LAR and PTPsigma underwent further proteolytical processing upon treatment of cells with either calcium ionophore A23187 or phorbol ester TPA. Induction of LAR processing by TPA in 293 cells did require overexpression of PKCalpha. Induced proteolysis resulted in shedding of the extracellular domains of both PTPases. This was in agreement with the identification of a specific PTPsigma cleavage site between amino acids Pro821 and Ile822. Confocal microscopy studies identified adherens junctions and desmosomes as the preferential subcellular localization for both PTPases matching that of plakoglobin. Consistent with this observation, we found direct association of plakoglobin and beta-catenin with the intracellular domain of LAR in vitro. Taken together, these data suggested an involvement of LAR and PTPsigma in the regulation of cell contacts in concert with cell adhesion molecules of the cadherin/catenin family. After processing and shedding of the extracellular domain, the catalytically active intracellular portions of both PTPases were internalized and redistributed away from the sites of cell-cell contact, suggesting a mechanism that regulates the activity and target specificity of these PTPases. Calcium withdrawal, which led to cell contact disruption, also resulted in internalization but was not associated with prior proteolytic cleavage and shedding of the extracellular domain. We conclude that the subcellular localization of LAR and PTPsigma is regulated by at least two independent mechanisms, one of which requires the presence of their extracellular domains and one of which involves the presence of intact cell-cell contacts.

Red sea floor origin: rare-Earth evidence.

Abundance patterns of rare earths of submarine tholeiitic basalts from the axial trough of the Red Sea resemble those of basalts from mid-ocean ridges but are distinct from shield or plateau basalts of tholeiitic composition. These results imply that à similar magmatic process, related to spreading of sea floors, operates beneath the axial trough of the Red Sea and the crest of mid-ocean ridges.

Evolution of the ratio of strontium-87 to strontium-86 in seawater from cretaceous to present.

A detailed record of the strontium-87 to strontium-86 ratio in seawater during the last 100 million years was determined by measuring this ratio in 137 well-preserved and well-dated fossil foraminifera samples. Sample preservation was evaluated from scanning electron microscopy studies, measured strontium-calcium ratios, and pore water strontium isotope ratios. The evolution of the strontium isotopic ratio in seawater offers a means to evaluate long-term changes in the global strontium isotope mass balance. Results show that the marine strontium isotope composition can be used for correlating and dating well-preserved authigenic marine sediments throughout much of the Cenozoic to a precision of +/-1 million years. The strontium-87 to strontium-86 ratio in seawater increased sharply across the Cretaceous/Tertiary boundary, but this feature is not readily explained as strontium input from a bolide impact on land.

Rare earths in hawaiian basalts.

Rare-earth elements have been determined by neutron activation analysis in 20 basalts from the Hawaiian Islands. The abundance patterns of these elements form groups coinciding closely with groupings based on other evidence, and a fractional crystallization mechanism for change in rare earth abundance is implied.