Collapse of the vortex-lattice inductance and shear modulus at the melting transition in untwinned YBa2Cu3O7\rm YBa_2Cu_3O_7

The complex resistivity $\hat{\rho}(\omega)$ of the vortex lattice in an untwinned crystal of 93-K $\rm YBa_2Cu_3O_7$ has been measured at frequencies $\omega/2\pi$ from 100 kHz to 20 MHz in a 2-Tesla field $\bf H\parallel c$, using a 4-probe RF transmission technique that enables continuous measurements versus $\omega$ and temperature $T$. As $T$ is increased, the inductance ${\cal L}_s(\omega) ={\rm Im} \hat{\rho}(\omega)/ \omega$ increases steeply to a cusp at the melting temperature $T_m$, and then undergoes a steep collapse consistent with vanishing of the shear modulus $c_{66}$. We discuss in detail the separation of the vortex-lattice inductance from the `volume' inductance, and other skin-depth effects. To analyze the spectra, we consider a weakly disordered lattice with a low pin density. Close fits are obtained to $\rho_1(\omega)$ over 2 decades in $\omega$. Values of the pinning parameter $\kappa$ and shear modulus $c_{66}$ obtained show that $c_{66}$ collapses by over 4 decades at $T_m$, whereas $\kappa$ remains finite.Comment: 11 pages, 8 figures, Phys. Rev. B, in pres

TFPIα Interacts with FVa and FXa to Inhibit Prothrombinase During the Initiation of Coagulation

Tissue factor pathway inhibitor α (TFPIα) inhibits prothrombinase, the thrombin-generating complex of factor Xa (FXa) and factor Va (FVa), during the initiation of coagulation. This inhibition requires binding of a conserved basic region within TFPIα to a conserved acidic region in FXa-activated and platelet-released FVa. In this study, the contribution of interactions between TFPIα and the FXa active site and FVa heavy chain to prothrombinase inhibition were examined to further define the inhibitory biochemistry. Removal of FXa active site binding by mutation or by deletion of the second Kunitz domain (K2) of TFPIα produced 17- or 34-fold weaker prothrombinase inhibition, respectively, establishing that K2 binding to the FXa active site is required for efficient inhibition. Substitution of the TFPIα basic region uncharged residues (Leu252, Ile253, Thr255) with Ala (TFPI-AAKA) produced 5.8-fold decreased inhibition. This finding was confirmed using a basic region peptide (Leu252-Lys261) and Ala substitution peptides, which established that the uncharged residues are required for prothrombinase inhibitory activity but not for binding the FVa acidic region. This suggests that the uncharged residues mediate a secondary interaction with FVa subsequent to acidic region binding. This secondary interaction seems to be with the FVa heavy chain, because the FV Leiden mutation weakened prothrombinase inhibition by TFPIα but did not alter TFPI-AAKA inhibitory activity. Thus, efficient inhibition of prothrombinase by TFPIα requires at least 3 intermolecular interactions: (1) the TFPIα basic region binds the FVa acidic region, (2) K2 binds the FXa active site, and (3) Leu252-Thr255 binds the FVa heavy chain

Home‐Based Cardiac Rehabilitation Alone and Hybrid With Center‐Based Cardiac Rehabilitation in Heart Failure: A Systematic Review and Meta‐Analysis

Background Center‐based cardiac rehabilitation (CBCR) has been shown to improve outcomes in patients with heart failure (HF). Home‐based cardiac rehabilitation (HBCR) can be an alternative to increase access for patients who cannot participate in CBCR. Hybrid cardiac rehabilitation (CR) combines short‐term CBCR with HBCR, potentially allowing both flexibility and rigor. However, recent data comparing these initiatives have not been synthesized. Methods and Results We performed a meta‐analysis to compare functional capacity and health‐related quality of life (hr‐QOL) outcomes in HF for (1) HBCR and usual care, (2) hybrid CR and usual care, and (3) HBCR and CBCR. A systematic search in 5 standard databases for randomized controlled trials was performed through January 31, 2019. Summary estimates were pooled using fixed‐ or random‐effects (when I2\u3e50%) meta‐analyses. Standardized mean differences (95% CI) were used for distinct hr‐QOL tools. We identified 31 randomized controlled trials with a total of 1791 HF participants. Among 18 studies that compared HBCR and usual care, participants in HBCR had improvement of peak oxygen uptake (2.39 mL/kg per minute; 95% CI, 0.28–4.49) and hr‐QOL (16 studies; standardized mean difference: 0.38; 95% CI, 0.19–0.57). Nine RCTs that compared hybrid CR with usual care showed that hybrid CR had greater improvements in peak oxygen uptake (9.72 mL/kg per minute; 95% CI, 5.12–14.33) but not in hr‐QOL (2 studies; standardized mean difference: 0.67; 95% CI, −0.20 to 1.54). Five studies comparing HBCR with CBCR showed similar improvements in functional capacity (0.0 mL/kg per minute; 95% CI, −1.93 to 1.92) and hr‐QOL (4 studies; standardized mean difference: 0.11; 95% CI, −0.12 to 0.34). Conclusions HBCR and hybrid CR significantly improved functional capacity, but only HBCR improved hr‐QOL over usual care. However, both are potential alternatives for patients who are not suitable for CBCR

Cloning and expression of a human neutral amino acid transporter with structural similarity to the glutamate transporter gene family

A cDNA was isolated from human brain that encodes an amino acid sequence 34-39% identical to previously published glutamate transporter sequences. Injection of RNA transcribed from this cDNA into Xenopus oocytes resulted in expression of a transport activity with the properties of the neutral amino acid uptake system ASC. Superfusion of alanine, serine, and cysteine evoked sodium-dependent inward currents in voltage-clamped oocytes expressing the transporter. These currents were dose-dependent, stereospecific, and saturable, with Km values ranging from 29 to 88 microM. Northern blot analyses revealed ubiquitous expression of this gene, termed ASCT1, consistent with the general metabolic role ascribed to system ASC

Pharmacogenetic testing affects choice of therapy among women considering tamoxifen treatment

Abstract Background Pharmacogenetic testing holds major promise in allowing physicians to tailor therapy to patients based on genotype. However, there is little data on the impact of pharmacogenetic test results on patient and clinician choice of therapy. CYP2D6 testing among tamoxifen users offers a potential test case of the use of pharmacogenetic testing in the clinic. We evaluated the effect of CYP2D6 testing in clinical practice to determine whether genotype results affected choice of hormone therapy in a prospective cohort study. Methods Women planning to take or currently taking tamoxifen were considered eligible. Participants were enrolled in an informational session that reviewed the results of studies of CYP2D6 genotype on breast cancer recurrence. CYP2D6 genotyping was offered to participants using the AmpliChip CYP450 Test. Women were classified as either poor, intermediate, extensive or ultra-rapid metabolizers. Results were provided to clinicians without specific treatment recommendations. Follow-up was performed with a structured phone interview 3 to 6 months after testing to evaluate changes in medication. Results A total of 245 women were tested and 235 completed the follow-up survey. Six of 13 (46%) women classified as poor metabolizers reported changing treatment compared with 11 of 218 (5%) classified as intermediate, extensive or ultra-rapid metabolizers (P < 0.001). There was no difference in treatment choices between women classified as intermediate and extensive metabolizers. In multi-variate models that adjusted for age, race/ethnicity, educational status, method of referral into the study, prior knowledge of CYP2D6 testing, the patients' CYP2D6 genotype was the only significant factor that predicted a change in therapy (odds ratio 22.8; 95% confidence interval 5.2 to 98.8). Genetic testing did not affect use of co-medications that interact with CYP2D6. Conclusions CYP2D6 genotype testing led to changes in therapy among poor metabolizers, even in the absence of definitive data that an alternative medicine improved outcomes. Pharmacogenetic testing can affect choice of therapy, even in the absence of definitive data on clinical impact

Global Gene Expression Profiling in Lung Tissues of Rat Exposed to Lunar Dust Particles

The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 12% respirable very fine dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to analyze the dynamics of global gene expression changes in lung tissues of rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in noseonly inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m3 of lunar dust. Animals were euthanized at 1 day and 13 weeks after the last inhalation exposure. After being lavaged, lung tissue from each animal was collected and total RNA was isolated. Four samples of each dose group were analyzed using Agilent Rat GE v3 microarray to profile global gene expression of 44K transcripts. After background subtraction, normalization, and log transformation, t tests were used to compare the mean expression levels of each exposed group to the control group. Correction for multiple testing was made using the method of Benjamini, Krieger, and Yekuteli (1) to control the false discovery rate. Genes with significant changes of at least 1.75 fold were identified as genes of interest. Both low and high doses of lunar dust caused dramatic, dosedependent global gene expression changes in the lung tissues. However, the responses of lung tissue to low dose lunar dust are distinguished from those of high doses, especially those associated with 61mg/m3 dust exposure. The data were further integrated into the Ingenuity system to analyze the gene ontology (GO), pathway distribution and putative upstream regulators and gene targets. Multiple pathways, functions, and upstream regulators have been identified in response to lunar dust induced damage in the lung tissue

Human embryonic myosin heavy chain cDNA Interspecies sequence conservation of the myosin rod, chromosomal locus and isoform specific transcription of the gene

AbstractA 3.6 kilobase cDNA clone coding for the human embryonic myosin heavy chain has been isolated and characterized from an expression library prepared from human fetal skeletal muscle. The derived amino acid sequence for the entire rod part of myosin shows 97% sequence homology between human and rat and a striking interspecies sequence conservation among the charged amino acid residues. The single copy gene is localized to human chromosome 17 and its expression in fetal skeletal muscle is developmentally regulated. The sequence information permits the design of isoform-specific probes for studies on the structure of the gene and its role in normal and defective human myogenesis.Myosin heavy chain cDNA; Nucleotide sequence; Amino acid sequence; Myosin rod; Chromosomal mapping; Gene transcription; (Human embryo