Visualizing metal ions in cells: An overview of analytical techniques, approaches, and probes

AbstractQuantifying the amount and defining the location of metal ions in cells and organisms are critical steps in understanding metal homeostasis and how dyshomeostasis causes or is a consequence of disease. A number of recent advances have been made in the development and application of analytical methods to visualize metal ions in biological specimens. Here, we briefly summarize these advances before focusing in more depth on probes for examining transition metals in living cells with high spatial and temporal resolution using fluorescence microscopy. This article is part of a Special Issue entitled: Cell Biology of Metals

Breast cancer detection using automated whole breast ultrasound and mammography in radiographically dense breasts

PurposeMammography, the standard method of breast cancer screening, misses many cancers, especially in dense-breasted women. We compared the performance and diagnostic yield of mammography alone versus an automated whole breast ultrasound (AWBU) plus mammography in women with dense breasts and/or at elevated risk of breast cancer.MethodsAWBU screening was tested in 4,419 women having routine mammography (Trial registrationClinicalTrials.gov Identifier: NCT00649337). Cancers occurring during the study and subsequent 1-year follow-up were evaluated. Sensitivity, specificity and positive predictive value (PPV) of biopsy recommendation for mammography alone, AWBU and mammography with AWBU were calculated.ResultsBreast cancer detection doubled from 23 to 46 in 6,425 studies using AWBU with mammography, resulting in an increase in diagnostic yield from 3.6 per 1,000 with mammography alone to 7.2 per 1,000 by adding AWBU. PPV for biopsy based on mammography findings was 39.0% and for AWBU 38.4%. The number of detected invasive cancers 10 mm or less in size tripled from 7 to 21 when AWBU findings were added to mammography.ConclusionAWBU resulted in significant cancer detection improvement compared with mammography alone. Additional detection and the smaller size of invasive cancers may justify this technology's expense for women with dense breasts and/or at high risk for breast cancer

A Noninvasive Brain-Computer Interface for Real-Time Speech Synthesis: The Importance of Multimodal Feedback.

We conducted a study of a motor imagery brain-computer interface (BCI) using electroencephalography to continuously control a formant frequency speech synthesizer with instantaneous auditory and visual feedback. Over a three-session training period, sixteen participants learned to control the BCI for production of three vowel sounds (/ textipa i/ [heed], / textipa A/ [hot], and / textipa u/ [who'd]) and were split into three groups: those receiving unimodal auditory feedback of synthesized speech, those receiving unimodal visual feedback of formant frequencies, and those receiving multimodal, audio-visual (AV) feedback. Audio feedback was provided by a formant frequency artificial speech synthesizer, and visual feedback was given as a 2-D cursor on a graphical representation of the plane defined by the first two formant frequencies. We found that combined AV feedback led to the greatest performance in terms of percent accuracy, distance to target, and movement time to target compared with either unimodal feedback of auditory or visual information. These results indicate that performance is enhanced when multimodal feedback is meaningful for the BCI task goals, rather than as a generic biofeedback signal of BCI progress

The serotonin transporter promotes a pathological estrogen metabolic pathway in pulmonary hypertension via cytochrome P450 1B1 pulmonary circulation

Pulmonary arterial hypertension (PAH) is a devastating vasculopathy that predominates in women and has been associated with dysregulated estrogen and serotonin signaling. Overexpression of the serotonin transporter (SERT+) in mice results in an estrogen-dependent development of pulmonary hypertension (PH). Estrogen metabolism by cytochrome P450 1B1 (CYP1B1) contributes to the pathogenesis of PAH, and serotonin can increase CYP1B1 expression in human pulmonary arterial smooth muscle cells (hPASMCs). We hypothesized that an increase in intracellular serotonin via increased SERT expression may dysregulate estrogen metabolism via CYP1B1 to facilitate PAH. Consistent with this hypothesis, we found elevated lung CYP1B1 protein expression in female SERT+ mice accompanied by PH, which was attenuated by the CYP1B1 inhibitor 2,3',4,5'-tetramethoxystilbene (TMS). Lungs from female SERT+ mice demonstrated an increase in oxidative stress that was marked by the expression of 8-hydroxyguanosine; however, this was unaffected by CYP1B1 inhibition. SERT expression was increased in monocrotaline-induced PH in female rats; however, TMS did not reverse PH in monocrotaline-treated rats but prolonged survival. Stimulation of hPASMCs with the CYP1B1 metabolite 16α-hydroxyestrone increased cellular proliferation, which was attenuated by an inhibitor (MPP) of estrogen receptor alpha (ERα) and a specific ERα antibody. Thus, increased intracellular serotonin caused by increased SERT expression may contribute to PAH pathobiology by dysregulation of estrogen metabolic pathways via increased CYP1B1 activity. This promotes PASMC proliferation by the formation of pathogenic metabolites of estrogen that mediate their effects via ERα. Our studies indicate that targeting this pathway in PAH may provide a promising antiproliferative therapeutic strategy

Making ARPES Measurements on Corrugated Monolayer Crystals: Suspended Exfoliated Single-Crystal Graphene

Free-standing exfoliated monolayer graphene is an ultra-thin flexible membrane, which exhibits out of plane deformation or corrugation. In this paper, a technique is described to measure the band structure of such free-standing graphene by angle-resolved photoemission. Our results show that photoelectron coherence is limited by the crystal corrugation. However, by combining surface morphology measurements of the graphene roughness with angle-resolved photoemission, energy dependent quasiparticle lifetime and bandstructure measurements can be extracted. Our measurements rely on our development of an analytical formulation for relating the crystal corrugation to the photoemission linewidth. Our ARPES measurements show that, despite significant deviation from planarity of the crystal, the electronic structure of exfoliated suspended graphene is nearly that of ideal, undoped graphene; we measure the Dirac point to be within 25 meV of $E_F$ . Further, we show that suspended graphene behaves as a marginal Fermi-liquid, with a quasiparticle lifetime which scales as $(E - E_F)^{-1}$; comparison with other graphene and graphite data is discussed

Instrumentation and Performance Analysis Plans for the HIFiRE Flight 2 Experiment

Supersonic combustion performance of a bi-component gaseous hydrocarbon fuel mixture is one of the primary aspects under investigation in the HIFiRE Flight 2 experiment. In-flight instrumentation and post-test analyses will be two key elements used to determine the combustion performance. Pre-flight computational fluid dynamics (CFD) analyses provide valuable information that can be used to optimize the placement of a constrained set of wall pressure instrumentation in the experiment. The simulations also allow pre-flight assessments of performance sensitivities leading to estimates of overall uncertainty in the determination of combustion efficiency. Based on the pre-flight CFD results, 128 wall pressure sensors have been located throughout the isolator/combustor flowpath to minimize the error in determining the wall pressure force at Mach 8 flight conditions. Also, sensitivity analyses show that mass capture and combustor exit stream thrust are the two primary contributors to uncertainty in combustion efficiency

Depth-dependent critical behavior in V2H

Using X-ray diffuse scattering, we investigate the critical behavior of an order-disorder phase transition in a defective "skin-layer" of V2H. In the skin-layer, there exist walls of dislocation lines oriented normal to the surface. The density of dislocation lines within a wall decreases continuously with depth. We find that, because of this inhomogeneous distribution of defects, the transition effectively occurs at a depth-dependent local critical temperature. A depth-dependent scaling law is proposed to describe the corresponding critical ordering behavior.Comment: 5 pages, 4 figure