549 research outputs found
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
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, a weak probe field exhibits a
multiple-peaked absorption spectrum with a constant peak separation .
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 . We report an experimental study in such a
bichromatically coupled three-level system in cold 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]
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
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
Alzheimer Disease Blood Biomarkers in Patients With Out-of-Hospital Cardiac Arrest
Importance: Blood phosphorylated tau (p-tau) and amyloid-β peptides (Aβ) are promising peripheral biomarkers of Alzheimer disease (AD) pathology. However, their potential alterations due to alternative mechanisms, such as hypoxia in patients resuscitated from cardiac arrest, are not known. Objective: To evaluate whether the levels and trajectories of blood p-tau, Aβ42, and Aβ40 following cardiac arrest, in comparison with neural injury markers neurofilament light (NfL) and total tau (t-tau), can be used for neurological prognostication following cardiac arrest. Design, Setting, and Participants: This prospective clinical biobank study used data from the randomized Target Temperature Management After Out-of-Hospital Cardiac Arrest (TTM) trial. Unconscious patients with cardiac arrest of presumed cardiac origin were included between November 11, 2010, and January 10, 2013, from 29 international sites. Serum analysis for serum NfL and t-tau were performed between August 1 and August 23, 2017. Serum p-tau, Aβ42, and Aβ40 were analyzed between July 1 and July 15, 2021, and between May 13 and May 25, 2022. A total of 717 participants from the TTM cohort were examined: an initial discovery subset (n = 80) and a validation subset. Both subsets were evenly distributed for good and poor neurological outcome after cardiac arrest. Exposures: Serum p-tau, Aβ42, and Aβ40 concentrations using single molecule array technology. Serum levels of NfL and t-tau were included as comparators. Main Outcomes and Measures: Blood biomarker levels at 24 hours, 48 hours, and 72 hours after cardiac arrest. Poor neurologic outcome at 6-month follow-up, defined according to the cerebral performance category scale as category 3 (severe cerebral disability), 4 (coma), or 5 (brain death). Results: This study included 717 participants (137 [19.1%] female and 580 male [80.9%]; mean [SD] age, 63.9 [13.5] years) who experienced out-of-hospital cardiac arrest. Significantly elevated serum p-tau levels were observed at 24 hours, 48 hours, and 72 hours in cardiac arrest patients with poor neurological outcome. The magnitude and prognostication of the change was greater at 24 hours (area under the receiver operating characteristic curve [AUC], 0.96; 95% CI, 0.95-0.97), which was similar to NfL (AUC, 0.94; 95% CI, 0.92-0.96). However, at later time points, p-tau levels decreased and were weakly associated with neurological outcome. In contrast, NfL and t-tau maintained high diagnostic accuracies, even 72 hours after cardiac arrest. Serum Aβ42 and Aβ40 concentrations increased over time in most patients but were only weakly associated with neurological outcome. Conclusions and Relevance: In this case-control study, blood biomarkers indicative of AD pathology demonstrated different dynamics of change after cardiac arrest. The increase of p-tau at 24 hours after cardiac arrest suggests a rapid secretion from the interstitial fluid following hypoxic-ischemic brain injury rather than ongoing neuronal injury like NfL or t-tau. In contrast, delayed increases of Aβ peptides after cardiac arrest indicate activation of amyloidogenic processing in response to ischemia
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
Evanescent light-matter Interactions in Atomic Cladding Wave Guides
Alkali vapors, and in particular rubidium, are being used extensively in
several important fields of research such as slow and stored light non-linear
optics3 and quantum computation. Additionally, the technology of alkali vapors
plays a major role in realizing myriad industrial applications including for
example atomic clocks magentometers8 and optical frequency stabilization.
Lately, there is a growing effort towards miniaturizing traditional
centimeter-size alkali vapor cells. Owing to the significant reduction in
device dimensions, light matter interactions are greatly enhanced, enabling new
functionalities due to the low power threshold needed for non-linear
interactions. Here, taking advantage of the mature Complimentary
Metal-Oxide-Semiconductor (CMOS) compatible platform of silicon photonics, we
construct an efficient and flexible platform for tailored light vapor
interactions on a chip. Specifically, we demonstrate light matter interactions
in an atomic cladding wave guide (ACWG), consisting of CMOS compatible silicon
nitride nano wave-guide core with a Rubidium (Rb) vapor cladding. We observe
the highly efficient interaction of the electromagnetic guided mode with the
thermal Rb cladding. The nature of such interactions is explained by a model
which predicts the transmission spectrum of the system taking into account
Doppler and transit time broadening. We show, that due to the high confinement
of the optical mode (with a mode area of 0.3{\lambda}2), the Rb absorption
saturates at powers in the nW regime.Comment: 10 Pages 4 Figures. 1 Supplementar
5-Thia-5-Deazaflavin, a 1e − -Transferring Flavin Analog
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65939/1/j.1432-1033.1979.tb12952.x.pd
Effects of urodilatin on natriuresis in cirrhosis patients with sodium retention
BACKGROUND: Sodium retention and ascites are serious clinical problems in cirrhosis. Urodilatin (URO) is a peptide with paracrine effects in decreasing sodium reabsorption in the distal nephron. Our aim was to investigate the renal potency of synthetic URO on urine sodium excretion in cirrhosis patients with sodium retention and ascites. METHODS: Seven cirrhosis patients with diuretics-resistant sodium retention received a short-term (90 min) infusion of URO in a single-blind, placebo-controlled cross-over study. In the basal state after rehydration the patients had urine sodium excretion < 50 mmol/24 h. RESULTS: URO transiently increased urine sodium excretion from 22 ± 16 μmol/min (mean ± SD) to 78 ± 41 μmol/min (P < 0.05) and there was no effect of placebo (29 ± 14 to 44 ± 32). The increase of URO's second messenger after the receptor, cGMP, was normal. URO had no effect on urine flow or on blood pressure. Most of the patients had highly elevated plasma levels of renin, angiotensin II and aldosterone and URO did not change these. CONCLUSION: The short-term low-dose URO infusion increased the sodium excretion of the patients. The increase was small but systematic and potentially clinically important for such patients. The small response contrasts the preserved responsiveness of the URO receptors. The markedly activated systemic pressor hormones in cirrhosis evidently antagonized the local tubular effects of URO
Ion Trap in a Semiconductor Chip
The electromagnetic manipulation of isolated atoms has led to many advances
in physics, from laser cooling and Bose-Einstein condensation of cold gases to
the precise quantum control of individual atomic ion. Work on miniaturizing
electromagnetic traps to the micrometer scale promises even higher levels of
control and reliability. Compared with 'chip traps' for confining neutral
atoms, ion traps with similar dimensions and power dissipation offer much
higher confinement forces and allow unparalleled control at the single-atom
level. Moreover, ion microtraps are of great interest in the development of
miniature mass spectrometer arrays, compact atomic clocks, and most notably,
large scale quantum information processors. Here we report the operation of a
micrometer-scale ion trap, fabricated on a monolithic chip using semiconductor
micro-electromechanical systems (MEMS) technology. We confine, laser cool, and
measure heating of a single 111Cd+ ion in an integrated radiofrequency trap
etched from a doped gallium arsenide (GaAs) heterostructure.Comment: 4 pages, 4 figure
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