An integrated atom-photon junction

Photonic chips that integrate guides, switches, gratings and other components, process vast amounts of information rapidly on a single device. A new branch of this technology becomes possible if the light is coupled to cold atoms in a junction of small enough cross section, so that small numbers of photons interact appreciably with the atoms. Cold atoms are among the most sensitive of metrological tools and their quantum nature also provides a basis for new information processing methods. Here we demonstrate a photonic chip which provides multiple microscopic junctions between atoms and photons. We use the absorption of light at a junction to reveal the presence of one atom on average. Conversely, we use the atoms to probe the intensity and polarisation of the light. Our device paves the way for a new type of chip with interconnected circuits of atoms and photons.Comment: 5 pages, 4 figure. Submitted to Nature Photonic

Experimental infection of sheep with ovine and bovine Dichelobacter nodosus isolates

AbstractThe aim of this study was, under experimental conditions, to investigate infection of Norwegian White sheep with ovine and bovine isolates of Dichelobacter nodosus of varying virulence. In addition, the efficacy of gamithromycin as a treatment for the experimentally induced infections was examined. The study was performed as a single foot inoculation using a boot. Four groups, each with six lambs, were inoculated with four different challenge strains (Group 1: benign bovine strain; Group 2: virulent bovine strain; Group 3: benign ovine strain; Group 4: virulent ovine strain). The main criterion to determine that infection was transferred was that D. nodosus isolate was obtained by culture. After the trial all lambs were treated with gamithromycin. Clinical symptoms of footrot developed in all groups, and when removing the boots two weeks after challenge, D. nodosus was isolated from 5 of 24 experimental lambs. All lambs tested negative for D. nodosus by PCR within six weeks after treatment with gamithromycin. This study strongly indicates that D. nodosus isolates from both sheep and cattle can be transferred to sheep under experimental conditions. The study also indicates that gamithromycin may be effective against D. nodosus

Plasma neurofilament light is a predictor of neurological outcome 12 h after cardiac arrest

Background: Previous studies have reported high prognostic accuracy of circulating neurofilament light (NfL) at 24–72 h after out-of-hospital cardiac arrest (OHCA), but performance at earlier time points and after in-hospital cardiac arrest (IHCA) is less investigated. We aimed to assess plasma NfL during the first 48 h after OHCA and IHCA to predict long-term outcomes. Methods: Observational multicentre cohort study in adults admitted to intensive care after cardiac arrest. NfL was retrospectively analysed in plasma collected on admission to intensive care, 12 and 48 h after cardiac arrest. The outcome was assessed at two to six months using the Cerebral Performance Category (CPC) scale, where CPC 1–2 was considered a good outcome and CPC 3–5 a poor outcome. Predictive performance was measured with the area under the receiver operating characteristic curve (AUROC). Results: Of 428 patients, 328 (77%) suffered OHCA and 100 (23%) IHCA. Poor outcome was found in 68% of OHCA and 55% of IHCA patients. The overall prognostic performance of NfL was excellent at 12 and 48 h after OHCA, with AUROCs of 0.93 and 0.97, respectively. The predictive ability was lower after IHCA than OHCA at 12 and 48 h, with AUROCs of 0.81 and 0.86 (p ≤ 0.03). AUROCs on admission were 0.77 and 0.67 after OHCA and IHCA, respectively. At 12 and 48 h after OHCA, high NfL levels predicted poor outcome at 95% specificity with 70 and 89% sensitivity, while low NfL levels predicted good outcome at 95% sensitivity with 71 and 74% specificity and negative predictive values of 86 and 88%. Conclusions: The prognostic accuracy of NfL for predicting good and poor outcomes is excellent as early as 12 h after OHCA. NfL is less reliable for the prediction of outcome after IHCA

Evaluation of a Covalent Library of Diverse Warheads (CovLib) Binding to JNK3, USP7, or p53

Theresa Klett,1,* Martin Schwer,1,* Larissa N Ernst,1,* Marc U Engelhardt,1 Simon J Jaag,2 Benedikt Masberg,2 Cornelius Knappe,2 Michael Lämmerhofer,2 Matthias Gehringer,3,4 Frank M Boeckler1,5 1Laboratory for Molecular Design & Pharmaceutical Biophysics, Institute of Pharmaceutical Sciences, Department of Pharmacy and Biochemistry, Eberhard Karls Universität Tübingen, Tübingen, 72076, Germany; 2Pharmaceutical (Bio-) Analysis, Institute of Pharmaceutical Sciences, Department of Pharmacy and Biochemistry, Eberhard Karls Universität Tübingen, Tübingen, 72076, Germany; 3Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, Department of Pharmacy and Biochemistry, Eberhard Karls Universität Tübingen, Tübingen, 72076, Germany; 4Medicinal Chemistry, Institute for Biomedical Engineering, Eberhard Karls Universität Tübingen, Tübingen, 72076, Germany; 5Interfaculty Institute for Biomedical Informatics (IBMI), Eberhard Karls Universität Tübingen, Tübingen, 72076, Germany*These authors contributed equally to this workCorrespondence: Frank M Boeckler, Laboratory for Molecular Design & Pharmaceutical Biophysics, Institute of Pharmaceutical Sciences, Department of Pharmacy and Biochemistry, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8 (Haus B), Tübingen, D – 72076, Germany, Tel +49 7071 29 74567, Email [email protected]: Over the last few years, covalent fragment-based drug discovery has gained significant importance. Thus, striving for more warhead diversity, we conceived a library consisting of 20 covalently reacting compounds. Our covalent fragment library (CovLib) contains four different warhead classes, including five α-cyanoacacrylamides/acrylates (CA), three epoxides (EO), four vinyl sulfones (VS), and eight electron-deficient heteroarenes with a leaving group (SNAr/SN).Methods: After predicting the theoretical solubility of the fragments by LogP and LogS during the selection process, we determined their experimental solubility using a turbidimetric solubility assay. The reactivities of the different compounds were measured in a high-throughput 5,5’-dithiobis-(2-nitrobenzoic acid) DTNB assay, followed by a (glutathione) GSH stability assay. We employed the CovLib in a (differential scanning fluorimetry) DSF-based screening against different targets: c-Jun N-terminal kinase 3 (JNK3), ubiquitin-specific protease 7 (USP7), and the tumor suppressor p53. Finally, the covalent binding was confirmed by intact protein mass spectrometry (MS).Results: In general, the purchased fragments turned out to be sufficiently soluble. Additionally, they covered a broad spectrum of reactivity. All investigated α-cyanoacrylamides/acrylates and all structurally confirmed epoxides turned out to be less reactive compounds, possibly due to steric hindrance and reversibility (for α-cyanoacrylamides/acrylates). The SNAr and vinyl sulfone fragments are either highly reactive or stable. DSF measurements with the different targets JNK3, USP7, and p53 identified reactive fragment hits causing a shift in the melting temperatures of the proteins. MS confirmed the covalent binding mode of all these fragments to USP7 and p53, while additionally identifying the SNAr-type electrophile SN002 as a mildly reactive covalent hit for p53.Conclusion: The screening and target evaluation of the CovLib revealed first interesting hits. The highly cysteine-reactive fragments VS004, SN001, SN006, and SN007 covalently modify several target proteins and showed distinct shifts in the melting temperatures up to +5.1 °C and − 9.1 °C. Keywords: covalent fragment-based drug discovery, differential scanning fluorimetry, 5,5’-dithiobis-(2-nitrobenzoic acid), intact protein mass spectrometry, glutathion

An Improved Neutron Electric Dipole Moment Experiment

A new measurement of the neutron EDM, using Ramsey's method of separated oscillatory fields, is in preparation at the new high intensity source of ultra-cold neutrons (UCN) at the Paul Scherrer Institute, Villigen, Switzerland (PSI). The existence of a non-zero nEDM would violate both parity and time reversal symmetry and, given the CPT theorem, might lead to a discovery of new CP violating mechanisms. Already the current upper limit for the nEDM (|d_n|<2.9E-26 e.cm) constrains some extensions of the Standard Model. The new experiment aims at a two orders of magnitude reduction of the experimental uncertainty, to be achieved mainly by (1) the higher UCN flux provided by the new PSI source, (2) better magnetic field control with improved magnetometry and (3) a double chamber configuration with opposite electric field directions. The first stage of the experiment will use an upgrade of the RAL/Sussex/ILL group's apparatus (which has produced the current best result) moved from Institut Laue-Langevin to PSI. The final accuracy will be achieved in a further step with a new spectrometer, presently in the design phase.Comment: Flavor Physics & CP Violation Conference, Taipei, 200

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

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