Topoisomer Differentiation of Molecular Knots by FTICR MS: Lessons from Class II Lasso Peptides

Lasso peptides constitute a class of bioactive peptides sharing a knotted structure where the C-terminal tail of the peptide is threaded through and trapped within an N-terminalmacrolactamring. The structural characterization of lasso structures and differentiation from their unthreaded topoisomers is not trivial and generally requires the use of complementary biochemical and spectroscopic methods. Here we investigated two antimicrobial peptides belonging to the class II lasso peptide family and their corresponding unthreaded topoisomers: microcin J25 (MccJ25), which is known to yield two-peptide product ions specific of the lasso structure under collisioninduced dissociation (CID), and capistruin, for which CID does not permit to unambiguously assign the lasso structure. The two pairs of topoisomers were analyzed by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR MS) upon CID, infrared multiple photon dissociation (IRMPD), and electron capture dissociation (ECD). CID and ECDspectra clearly permitted to differentiate MccJ25 from its non-lasso topoisomer MccJ25-Icm, while for capistruin, only ECD was informative and showed different extent of hydrogen migration (formation of c\bullet/z from c/z\bullet) for the threaded and unthreaded topoisomers. The ECD spectra of the triply-charged MccJ25 and MccJ25-lcm showed a series of radical b-type product ions {\eth}b0In{\TH}. We proposed that these ions are specific of cyclic-branched peptides and result from a dual c/z\bullet and y/b dissociation, in the ring and in the tail, respectively. This work shows the potentiality of ECD for structural characterization of peptide topoisomers, as well as the effect of conformation on hydrogen migration subsequent to electron capture

Investigation and compensation of the nonlinear response in photomultiplier tubes for quantitative single-shot measurements.

A concept for time-sensitive optical detectors is described that shows how to confirm whether the detection device is operating in the linear response regime. By evaluating the recorded time decay of a thermographic phosphor, even weak saturation effects far from obvious situations can be identified and further related to either optical or electrical saturation. The concept has been validated by running a PMT detector close to saturation and exposing it to the optical signal decay of two different thermographic phosphors, La(2)O(2)S:Eu and CdWO(4). It was confirmed that short but intense light exposures at the beginning of an individual time decay influence the detector response for the rest of the decaying signal including temporal areas, where the anode current has dropped well below the manufacturer specified current limit. Such situations are common when applying, e.g., phosphor thermometry where it is necessary to retrieve the full decay curve from a single-shot event, i.e., standard techniques based on single-photon counting are omitted. Finally, means of compensation are introduced in order to facilitate the retrieval of useful information from the measurement data when operation in the non-linear response regime is inevitable

Limit on Lorentz and CPT violation of the bound Neutron Using a Free Precession 3He/129Xe co-magnetometer

We report on the search for Lorentz violating sidereal variations of the frequency difference of co-located spin-species while the Earth and hence the laboratory reference frame rotates with respect to a relic background field. The co-magnetometer used is based on the detection of freely precessing nuclear spins from polarized 3He and 129Xe gas samples using SQUIDs as low-noise magnetic flux detectors. As result we can determine the limit for the equatorial component of the background field interacting with the spin of the bound neutron to be bn < 3.7 x 10^{-32} GeV (95 C.L.).Comment: 5 pages, 4 figure

Bichromatic electromagnetically induced transparency in cold rubidium atoms

In a three-level atomic system coupled by two equal-amplitude laser fields with a frequency separation 2$\delta$, a weak probe field exhibits a multiple-peaked absorption spectrum with a constant peak separation $\delta$. The corresponding probe dispersion exhibits steep normal dispersion near the minimum absorption between the multiple absorption peaks, which leads to simultaneous slow group velocities for probe photons at multiple frequencies separated by $\delta$. We report an experimental study in such a bichromatically coupled three-level $\Lambda$ system in cold $^{87}$Rb atoms. The multiple-peaked probe absorption spectra under various experimental conditions have been observed and compared with the theoretical calculations.Comment: RevTex, 4 pages, 6 figures, Email address: [email protected]

Treatment Options in Cushing’s Disease

Endogenous Cushing’s syndrome is a grave disease that requires a multidisciplinary and individualized treatment approach for each patient. Approximately 80% of all patients harbour a corticotroph pituitary adenoma (Cushing’s disease) with excessive secretion of adrenocorticotropin-hormone (ACTH) and, consecutively, cortisol. The goals of treatment include normalization of hormone excess, long-term disease control and the reversal of comorbidities caused by the underlying pathology. The treatment of choice is neurosurgical tumour removal of the pituitary adenoma. Second-line treatments include medical therapy, bilateral adrenalectomy and radiation therapy. Drug treatment modalities target at the hypothalamic/pituitary level, the adrenal gland and at the glucocorticoid receptor level and are commonly used in patients in whom surgery has failed. Bilateral adrenalectomy is the second-line treatment for persistent hypercortisolism that offers immediate control of hypercortisolism. However, this treatment option requires a careful individualized evaluation, since it has the disadvantage of permanent hypoadrenalism which requires lifelong glucocorticoid and mineralocorticoid replacement therapy and bears the risk of developing Nelson’s syndrome. Although there are some very promising medical therapy options it clearly remains a second-line treatment option. However, there are numerous circumstances where medical management of CD is indicated. Medical therapy is frequently used in cases with severe hypercortisolism before surgery in order to control the metabolic effects and help reduce the anestesiological risk. Additionally, it can help to bridge the time gap until radiotherapy takes effect. The aim of this review is to analyze and present current treatment options in Cushing’s disease

Cold atoms in videotape micro-traps

We describe an array of microscopic atom traps formed by a pattern of magnetisation on a piece of videotape. We describe the way in which cold atoms are loaded into one of these micro-traps and how the trapped atom cloud is used to explore the properties of the trap. Evaporative cooling in the micro-trap down to a temperature of 1 microkelvin allows us to probe the smoothness of the trapping potential and reveals some inhomogeneity produced by the magnetic film. We discuss future prospects for atom chips based on microscopic permanent-magnet structures.Comment: Submitted for EPJD topical issue "Atom chips: manipulating atoms and molecules with microfabricated structures

3D-surface reconstruction of cellular cryo-soft X-ray microscopy tomograms using semi-supervised deep learning

Cryo-soft X-ray tomography (cryo-SXT) is a powerful method to investigate the ultrastructure of cells, offering resolution in the tens of nm range and strong contrast for membranous structures without requirement for labeling or chemical fixation. The short acquisition time and the relatively large volumes acquired allow for fast acquisition of large amounts of tomographic image data. Segmentation of these data into accessible features is a necessary step in gaining biologically relevant information from cryo-soft X-ray tomograms. However, manual image segmentation still requires several orders of magnitude more time than data acquisition. To address this challenge, we have here developed an end-to-end automated 3D-segmentation pipeline based on semi-supervised deep learning. Our approach is suitable for high-throughput analysis of large amounts of tomographic data, while being robust when faced with limited manual annotations and variations in the tomographic conditions. We validate our approach by extracting three-dimensional information on cellular ultrastructure and by quantifying nanoscopic morphological parameters of filopodia in mammalian cells

A surface-patterned chip as a strong source of ultracold atoms for quantum technologies

Laser-cooled atoms are central to modern precision measurements. They are also increasingly important as an enabling technology for experimental cavity quantum electrodynamics, quantum information processing and matter–wave interferometry. Although significant progress has been made in miniaturizing atomic metrological devices, these are limited in accuracy by their use of hot atomic ensembles and buffer gases. Advances have also been made in producing portable apparatus that benefits from the advantages of atoms in the microkelvin regime. However, simplifying atomic cooling and loading using microfabrication technology has proved difficult. In this Letter we address this problem, realizing an atom chip that enables the integration of laser cooling and trapping into a compact apparatus. Our source delivers ten thousand times more atoms than previous magneto-optical traps with microfabricated optics and, for the first time, can reach sub-Doppler temperatures. Moreover, the same chip design offers a simple way to form stable optical lattices. These features, combined with simplicity of fabrication and ease of operation, make these new traps a key advance in the development of cold-atom technology for high-accuracy, portable measurement devices