A magnetic diagnostic suite for the Pegasus-III experiment.

Pegasus-III is an ultralow aspect ratio spherical tokamak providing a dedicated US experiment for comparative solenoid-free startup studies. A new magnetic diagnostic suite for equilibrium and low frequency (<200 kHz) magnetohydrodynamic mode analysis has been installed. These new diagnostics address the significant challenges of measuring magnetic field in a high noise environment with the majority constrained to fit in an 8 mm diagnostic gap on the high field side.

Implementation of an impurity diagnostic suite on the Pegasus-III experiment.

A suite of diagnostics used to assess impurity content and dynamics has been updated, upgraded, and installed on the Pegasus-III Experiment. Typical plasma parameters during local helicity injection start-up are τshot ∼ 10 ms, ne ∼ 1 × 1019 m-3, and Te ∼ 50 eV. The deployed diagnostics are compatible with this modest temperature and density regime and provide species identification, source localization, and estimation of radiation losses.

Exploring functional interplay amongst efflux pumps.

Bacterial efflux pumps exhibit functional interplay that can translate to additive or multiplicative effects on resistance to antimicrobial compounds. In diderm bacteria, two different efflux pump structural types - single-component inner membrane efflux pumps and cell envelope-spanning multicomponent systems - cooperatively export antimicrobials with cytoplasmic targets from the cell. Harnessing our recently developed efflux platform, which is built upon an extensively efflux-deficient strain of , here we explore interplay amongst a panel of diverse efflux pumps.

A genetic platform to investigate the functions of bacterial drug efflux pumps.

Efflux pumps are a serious challenge for the development of antibacterial agents. Overcoming efflux requires an in-depth understanding of efflux pump functions, specificities and the development of inhibitors. However, the complexities of efflux networks have limited such studies.

Using integrated data analysis to extend measurement capability (invited).

The analysis approach called integrated data analysis (IDA) provides a means to exploit all information present in multiple streams of raw data to produce the best inference of a plasma parameter. This contrasts with the typical approach in which information (data) from a single diagnostic is used to measure a given parameter, e.g.

Observation of Electron Bernstein Wave Heating in a Reversed Field Pinch.

The first observation of rf heating in a reversed field pinch (RFP) using the electron Bernstein wave (EBW) is demonstrated on the Madison Symmetric Torus. Propagation across and heating in a stochastic magnetic field is observed. Novel techniques are required to measure the suprathermal electron tail generated by EBW heating in the presence of intense Ohmic heating.

Complementary Glycomic Analyses of Sera Derived from Colorectal Cancer Patients by MALDI-TOF-MS and Microchip Electrophoresis.

Colorectal cancer is the fourth most prevalent cancer in the United States, yet there are no reliable noninvasive early screening methods available. Serum-based glycomic profiling has the necessary sensitivity and specificity to distinguish disease states and provide diagnostic potential for this deadly form of cancer. We applied microchip electrophoresis and MALDI-TOF-MS-based glycomic procedures to 20 control serum samples and 42 samples provided by patients diagnosed with colorectal cancer.

Note: Effect of photodiode aluminum cathode frame on spectral sensitivity in the soft x-ray energy band.

Silicon photodiodes used for soft x-ray detection typically have a thin metal electrode partially covering the active area of the photodiode, which subtly alters the spectral sensitivity of the photodiode. As a specific example, AXUV4BST photodiodes from International Radiation Detectors have a 1.0 μm thick aluminum frame covering 19% of the active area of the photodiode, which attenuates the measured x-ray signal below ~6 keV.

Comparative profiling of N-glycans isolated from serum samples of ovarian cancer patients and analyzed by microchip electrophoresis.

Ovarian cancer is the fifth leading cause of cancer-related mortalities for women in the United States and the most lethal gynecological cancer. Aberrant glycosylation has been linked to several human diseases, including ovarian cancer, and accurate measurement of changes in glycosylation may provide relevant diagnostic and prognostic information. In this work, we used microchip electrophoresis coupled with laser-induced fluorescence detection to determine quantitative differences among the N-glycan profiles of control individuals and late-stage recurrent ovarian cancer patients prior to and after an experimental drug treatment that combined docetaxel and imatinib mesylate.

High-performance double-filter soft x-ray diagnostic for measurement of electron temperature structure and dynamics.

A new soft x-ray (SXR) T(e) and tomography diagnostic has been developed for MST that can be used for simultaneous SXR spectrum measurement, tomographically reconstructed emissivity, and reconstructed and line-of-sight electron temperature. The diagnostic utilizes high-performance differential transimpedance amplifiers (gain 10(5)-10(9)) to provide fast time response (up to 125 kHz), allowing for the study of plasma structure dynamics. SXR double-foil T(e) measurements are consistent with Thomson scattering.

Smoking and lung cancer-induced changes in N-glycosylation of blood serum proteins.

Glycosylation is a key post-translational protein modification which appears important in malignant transformation and tumor metastasis. Abnormal glycosylation of different proteins can often be measured in the blood serum. In this study, we extend our serum-based structural investigations to samples provided by patients diagnosed with lung cancer, paying particular attention to the effects of smoking on the serum glycomic traces.

Glycomic and proteomic profiling of pancreatic cyst fluids identifies hyperfucosylated lactosamines on the N-linked glycans of overexpressed glycoproteins.

Pancreatic cancer is now the fourth leading cause of cancer deaths in the United States, and it is associated with an alarmingly low 5-year survival rate of 5%. However, a patient's prognosis is considerably improved when the malignant lesions are identified at an early stage of the disease and removed by surgical resection. Unfortunately, the absence of a practical screening strategy and clinical diagnostic test for identifying premalignant lesions within the pancreas often prevents early detection of pancreatic cancer.

Examination of glycan profiles from IgG-depleted human immunoglobulins facilitated by microscale affinity chromatography.

Among the most important proteins involved in disease and healing processes are the immunoglobulins (Igs). Although many of the Igs have been studied through proteomics, aside from IgG, immunoglobulin carbohydrates have not been extensively characterized in different states of health. It seems valuable to develop techniques that permit an understanding of changes in the structures and abundances of Ig glycans in the context of disease onset and progression.

N-linked glycan structures and their expressions change in the blood sera of ovarian cancer patients.

Glycosylated proteins play important roles in a broad spectrum of biochemical and biological processes, and prior reports have suggested that changes in protein glycosylation occur during cancer initiation and progression. Ovarian cancer (OC) is a fatal malignancy, most commonly diagnosed after the development of metastases. Therefore, early detection of OC is key to improving survival.

Hedgehog-producing cancer cells respond to and require autocrine Hedgehog activity.

A number of Smoothened (SMO) pathway antagonists are currently undergoing clinical trials as anticancer agents. These drugs are proposed to attenuate tumor growth solely through inhibition of Hedgehog (HH), which is produced in tumor cells but acts on tumor stromal cells. The pivotal argument underlying this model is that the growth-inhibitory properties of SMO antagonists on HH-producing cancer cells are due to their off-target effects.

A new double-foil soft x-ray array to measure T(e) on the MST reversed field pinch.

A soft x-ray (SXR) diagnostic to measure electron temperature on the Madison Symmetric Torus using two complementary methods is presented. Both methods are based on the double-foil technique, which calculates electron temperature via the ratio of SXR bremsstrahlung emission from the plasma in two different energy ranges. The tomographic emissivity method applies the double-foil technique to a tomographic reconstruction of SXR emissivity, creating a two-dimensional map of temperature throughout the plasma.

An upgraded x-ray spectroscopy diagnostic on MST.

An upgraded x-ray spectroscopy diagnostic is used to measure the distribution of fast electrons in MST and to determine Z(eff) and the particle diffusion coefficient D(r). A radial array of 12 CdZnTe hard-x-ray detectors measures 10-150 keV Bremsstrahlung from fast electrons, a signature of reduced stochasticity and improved confinement in the plasma. A new Si soft-x-ray detector measures 2-10 keV Bremsstrahlung from thermal and fast electrons.

One institution's experience in implementing protocols for glycemic management.

The objective for monitoring blood glucose is to determine the need for intervention. This article describes an institution's comprehensive program of protocols and education initiated to manage inpatient hyperglycemia.

The full-length unprocessed hedgehog protein is an active signaling molecule.

The hedgehog (HH) family of ligands plays an important instructional role in metazoan development. HH proteins are initially produced as approximately 45-kDa full-length proteins, which undergo an intramolecular cleavage to generate an amino-terminal product that subsequently becomes cholesterol-modified (HH-Np). It is well accepted that this cholesterol-modified amino-terminal cleavage product is responsible for all HH-dependent signaling events.

Enzymatic/chemical release of O-glycans allowing MS analysis at high sensitivity.

As the role of O-linked oligosaccharides have been demonstrated to be increasingly important in numerous medical conditions, it is imperative to develop new techniques allowing their analysis at high sensitivity. While mass spectrometry (MS) provides adequate measurements of important O-linked oligosaccharides glycans and their profiles, the release from glycoproteins has not been sufficiently addressed for the needs of biomedical applications. This work describes a new strategy, involving the combination of a complete enzymatic degradation with a chemical release during the solid-phase permethylation of O-linked oligosaccharides.

Sonic hedgehog mutations identified in holoprosencephaly patients can act in a dominant negative manner.

Sonic hedgehog (SHH) plays an important instructional role in vertebrate development, as exemplified by the numerous developmental disorders that occur when the SHH pathway is disrupted. Mutations in the SHH gene are the most common cause of sporadic and inherited holoprosencephaly (HPE), a developmental disorder that is characterized by defective prosencephalon development. SHH HPE mutations provide a unique opportunity to better understand SHH biogenesis and signaling, and to decipher its role in the development of HPE.

Glycomic profiling of invasive and non-invasive breast cancer cells.

Quantitative profiling of glycans with different structures appears essential for a better understanding of the cellular adhesion phenomena associated with malignant transformation and the underlying aberrant glycosylation of cancer cells. Using the recently developed glycomic techniques and mass-spectrometric measurements, we compare the N-linked and O-linked oligosaccharide profiles for different breast cancer cell lines with those of normal epithelial cells. Statistically significant differences in certain neutral, sialylated and fucosylated structures are readily discerned through quantitative measurements, indicating a potential of distinguishing invasive and non-invasive cancer attributes.

Breast cancer diagnosis and prognosis through quantitative measurements of serum glycan profiles.

Background: Glycosylated proteins play important roles in cell-to-cell interactions, immunosurveillance, and a variety of receptor-mediated and specific protein functions through a highly complex repertoire of glycan structures. Aberrant glycosylation has been implicated in cancer for many years.

Methods: We performed specific MALDI mass spectrometry (MS)-based glycomic profile analyses of permethylated glycans in sera from breast cancer patients (12, stage I; 11, stage II; 9, stage III; and 50, stage IV) along with sera from 27 disease-free women.

Comparative glycomic mapping through quantitative permethylation and stable-isotope labeling.

Comparative glycan quantification has thus far been a challenging task due to the lack of sensitive and reproducible analytical techniques. We introduce here a combination of quantitative permethylation and isotope labeling of glycans as an approach (C-GlycoMAP) allowing precise comparison between different samples in a single MALDI-MS analysis. Samples are either methylated or deuteriomethylated prior to their mixing and mass spectrometric acquisitions.