High-resolution imaging of ultracold fermions in microscopically tailored optical potentials

We report on the local probing and preparation of an ultracold Fermi gas on the length scale of one micrometer, i.e. of the order of the Fermi wavelength. The essential tool of our experimental setup is a pair of identical, high-resolution microscope objectives. One of the microscope objectives allows local imaging of the trapped Fermi gas of 6Li atoms with a maximum resolution of 660 nm, while the other enables the generation of arbitrary optical dipole potentials on the same length scale. Employing a 2D acousto-optical deflector, we demonstrate the formation of several trapping geometries including a tightly focussed single optical dipole trap, a 4x4-site two-dimensional optical lattice and a 8-site ring lattice configuration. Furthermore, we show the ability to load and detect a small number of atoms in these trapping potentials. A site separation of down to one micrometer in combination with the low mass of 6Li results in tunneling rates which are sufficiently large for the implementation of Hubbard-models with the designed geometries.Comment: 15 pages, 6 figure

A Randomized Controlled Comparison of Image Quality

Background The purpose of the present study was to compare the image quality of spinal magnetic resonance (MR) imaging performed on a high-field horizontal open versus a short-bore MR scanner in a randomized controlled study setup. Methods Altogether, 93 (80% women, mean age 53) consecutive patients underwent spine imaging after random assignement to a 1-T horizontal open MR scanner with a vertical magnetic field or a 1.5-T short-bore MR scanner. This patient subset was part of a larger cohort. Image quality was assessed by determining qualitative parameters, signal-to-noise (SNR) and contrast-to-noise ratios (CNR), and quantitative contour sharpness. Results The image quality parameters were higher for short-bore MR imaging. Regarding all sequences, the relative differences were 39% for the mean overall qualitative image quality, 53% for the mean SNR values, and 34–37% for the quantitative contour sharpness (P<0.0001). The CNR values were also higher for images obtained with the short-bore MR scanner. No sequence was of very poor (nondiagnostic) image quality. Scanning times were significantly longer for examinations performed on the open MR scanner (mean: 32±22 min versus 20±9 min; P<0.0001). Conclusions In this randomized controlled comparison of spinal MR imaging with an open versus a short-bore scanner, short-bore MR imaging revealed considerably higher image quality with shorter scanning times

Miniaturized high-performance drift tube ion mobility spectrometer

Developing powerful hand-held drift tube ion mobility spectrometers (IMS) requires small, lightweight drift tubes with high analytical performance. In this work, we present an easy-to-manufacture, miniaturized drift tube ion mobility spectrometer, which is manufactured from polyether ether ketone, stainless steel foils and printed circuit boards. It is possible to operate the drift tube IMS with a radioactive 3H ionization source or a non-radioactive X-ray ionization source with 3 kV acceleration voltage. The drift tube design provides high resolving power of Rp = 63 at a drift length of just 40 mm, 15 mm × 15 mm in cross-section (outer dimensions) and a drift voltage of 2.5 kV. The limits of detection for less than one second of averaging are 40 pptv for dimethyl-methylphosphonate and 30 pptv for methyl salicylate. For demonstration, the miniaturized drift tube IMS is integrated into a stand-alone battery-powered mobile device, including a closed gas-loop, high performance driver electronics and wireless data transmission. In a proof-of-concept study, this device was tested in an international field evaluation exercise to detect the release of a volatile, hazardous substance inside a large entry hall

Local accuracy of actual intraoral scanning systems for single-tooth preparations in vitro

BACKGROUND The authors evaluated the local accuracy of intraoral scanning (IOS) systems for single-tooth preparation impressions with an in vitro setup. METHODS The authors digitized a mandibular complete-arch model with 2 full-contour crowns and 2 multisurface inlay preparations with a highly accurate reference scanner. Teeth were made from zirconia-reinforced glass ceramic material to simulate toothlike optical behavior. Impressions were obtained either conventionally (PRESIDENT, Coltène) or digitally using the IOS systems TRIOS 3 and TRIOS 3 using insane scan speed mode (3Shape), Medit i500, Version 1.2.1 (Medit), iTero Element 2, Version 1.7 (Align Technology), CS 3600, Version 3.1.0 (Carestream Dental), CEREC Omnicam, Version 4.6.1, CEREC Omnicam, Version 5.0.0, and Primescan (Dentsply Sirona). Impressions were repeated 10 times per test group. Conventional (CO) impressions were poured with type IV gypsum and digitized with a laboratory scanner. The authors evaluated trueness and precision for preparation margin (MA) and preparation surface (SU) using 3-dimensional superimposition and 3-dimensional difference analysis method using (95% - 5%) / 2 percentile values. Statistical analysis was performed using Kruskal-Wallis test. Results were presented as median (interquartile range) values in micrometers. RESULTS The authors found statistically significant differences for MA and SU among different test groups for both trueness and precision (P < .05). Median (interquartile range) trueness values ranged from 11.8 (2.0) μm (CO) up to 40.5 (10.9) μm (CEREC Omnicam, Version 5.0.0) for SU parameter and from 17.7 (2.6) μm (CO) up to 55.9 (15.5) μm (CEREC Omnicam, Version 5.0.0) for MA parameter. CONCLUSIONS IOS systems differ in terms of local accuracy. Preparation MA had higher deviations compared with preparation SU for all test groups. PRACTICAL IMPLICATIONS Trueness and precision values for both MA and SU of single-unit preparations are equal or close to CO impression for several IOS systems

Thymosin β4 in humanem Speichel: Quellen und Einflussfaktoren

Background and objectives The oral fluids saliva and gingival crevicular fluid seem to be very promising sources for the investigation of thymosin ß4 as they are readily available. Recent investigations revealed thymosin ß4 to be present in whole saliva and provided meaningful insights into the possible function of oral thymosin ß4 reported to influence dentinogenesis and the development of the oral cavity. The data mentioned reflect an increasing interest for oral thymosin ß4, but its source in the oral cavity, the influences for its secretion, the secretion process itself, its function and its possible diagnostic value for diseases of the oral cavity are far from being understood. We therefore investigated possible sources and influences for the secretion of thymosin ß4 trying to find an answer for its possible functions in the oral cavity. Methods Determination and identification of thymosin ß4 was carried out by RP-HPLC and MALDI-TOF. At first we studied the protein concentration and the thymosin ß4 concentration in whole saliva as a function of time in two different age groups. We then tried to find out different possible sources for thymosin ß4 in the oral fluids. Afterwards we investigated the thymosin ß4 concentration in the gingival crevicular fluid from periodontal diseased patients and compared it to healthy test persons. Concerning a possible release of thymosin ß4 from cells into the gingival crevicular fluid we tested the influence of increased occlusal contact on the concentration of thymosin ß4 present in the gingival crevicular fluid. Results At first whole saliva was analyzed: independent of the test persons´ age presence of oral thymosin ß4 varied considerably even showing significant changes when new specimens were taken after two weeks. The mean concentration of thymosin ß4 was determined to be higher in older than in younger test persons. We revealed the gingival crevicular fluid to be the main source of oral thymosin ß4 by performing separate analysis of whole saliva, glandular saliva and gingival crevicular fluid. The thymosin ß4 concentration in both healthy and diseased test persons varied not only interindividually as yet observed in whole saliva but also intraindividually. The mean concentration of thymosin ß4 was determined to be lower in periodontal diseased patients whose mean volume of the gingival crevicular fluid was determined to be higher. Finally we did not find any significant differences of the thymosin ß4 concentration in samples of gingival crevicular fluid obtained with or without increased occlusal contact. Conclusions We revealed the gingival crevicular fluid to be the main source for oral thymosin ß4 and demonstrated that its concentration is influenced by factors like the time of sample collection and the test persons´ age and periodontal status. Our findings suggest that there have to be special mechanisms to ensure the local enrichment of thymosin ß4 in the gingival connective tissue and the gingival crevicular fluid. Microvascular leakage and direct systemic migration of thymosin ß4 into the gingival crevicular fluid cannot explain the high extracellular concentrations of thymosin ß4 as they are significant higher than in whole blood. While the influx of the gingival crevicular fluid depends on mediators of vascular permeability, the emigration of thymosin ß4 into the gingival crevice might be influenced by specific mediators yet unidentified. Due to these high concentrations, thymosin ß4 might fulfill essential functions in the oral environment.Hintergrund und Ziele Die oralen Flüssigkeiten Speichel und Sulkusfluid stellen vielversprechende Quellen für die Untersuchung von Thymosin ß4 dar, da sie schnell und vor allem nicht invasiv gewonnen werden können. Das Auftreten von Thymosin ß4 in humanem Speichel konnte in einer kürzlich veröffentlichten Studie nachgewiesen werden. Weitere Studien befassten sich mit einer möglichen Funktion des oralen Thymosin ß4, das unter anderem die Dentinogenese und die Entwicklung der Mundhöhle beeinflusst. Wenngleich orales Thymosin ß4 in letzter Zeit verstärkt Gegenstand der Forschung gewesen ist, so herrscht dennoch weiterhin Unklarheit über mögliche Quellen und Einflussfaktoren für das Auftreten von Thymosin ß4 in humanem Speichel. Ein möglicher Freisetzungsmechanismus des Peptids und ein eventueller Zusammenhang des Auftretens von oralem Thymosin ß4 mit oralen Erkrankungen wurden ebenfalls noch nicht analysiert. In dieser Arbeit werden demnach verschiedene Quellen und Einflussfaktoren für das Auftreten von Thymosin ß4 in humanem Speichel untersucht, mit dem Ziel, die funktionelle Bedeutung dieses Peptids innerhalb der Mundhöhle genauer zu verstehen. Methoden Der Nachweis und die quantitative Bestimmung von oralem Thymosin ß4 erfolgte mittels RP-HPLC und MALDI-TOF. Zunächst wurden die Proteinkonzentration und die Konzentration von Thymosin ß4 in humanem Speichel in Abhängigkeit von der Zeit in zwei unterschiedlichen Altersgruppen untersucht. Anschließend wurden verschiedene Quellen für orales Thymosin ß4 analysiert. Danach erfolgte die Untersuchung der Thymosin ß4 Konzentration im Sulkusfluid bei parodontal gesunden und erkrankten Probanden. Zuletzt wurde der Einfluss einer verstärkten okklusalen Belastung auf die Thymosin ß4 Konzentration im Sulkusfluid untersucht. Ergebnisse Die Thymosin ß4 Konzentration im Gesamtspeichel variierte unabhängig vom Alter der Probanden sehr stark und war über die Zeit nicht konstant. Die durchschnittliche Thymosin ß4 Konzentration war bei älteren Probanden größer als bei jüngeren Probanden. Das Sulkusfluid konnte als Hauptquelle für das orale Thymosin ß4 ausgemacht werden. Drüsenspeichel enthielt keine nachweisbaren Konzentrationen an Thymosin ß4. Bei der Analyse der Thymosin ß4 Konzentration im Sulkusfluid parodontal erkrankter und gesunder Probanden ergaben sich neben den bereits beobachteten interindividuellen zusätzlich noch unterschiedlich starke intraindividuelle Schwankungen. Bei parodontal erkrankten Probanden wurden bei generell erhöhten Volumina an Sulkusfluid durchschnittlich geringere Konzentrationen an Thymosin ß4 nachgewiesen. Eine verstärkte okklusale Belastung führte zu keiner deutlichen Veränderung der Thymosin ß4 Konzentration im Sulkusfluid. Praktische Schlussfolgerungen In dieser Arbeit konnte nachgewiesen werden, dass das Sulkusfluid die Hauptquelle des oralen Thymosin ß4 darstellt und dass dessen Konzentration von Einflussfaktoren wie dem Zeitpunkt der Probennahme, dem Alter und dem Parodontalstatus des Probanden abhängig ist. Die Ergebnisse legen zudem nahe, dass es besondere Mechanismen der lokalen Anreicherung von Thymosin ß4 im gingivalen Bindegewebe und eine dementsprechende Freisetzung in das Sulkusfluid geben muss. Während die Produktion des Sulkusfluids von Mediatoren der vaskulären Permeabilität abhängig ist, könnte der Übertritt von Thymosin ß4 in den gingivalen Sulkus von bisher nicht identifizierten spezifischen Mediatoren gesteuert werden. In anderen Geweben oder Flüssigkeiten, wie beispielsweise im Blut, wurden bisher wesentlich geringere Thymosin ß4 Konzentrationen nachgewiesen. Deshalb sollte das in erstaunlich hohen Konzentrationen auftretende orale Thymosin ß4 von großer funktioneller Bedeutung sein

Raloxifene-derived PhzB ligands as potential Pseudomonas aeruginosa anti-infectives

Die Zunahme der mikrobakteriellen Resistenz gegen Antibiotika ist eine große Belastung für das globale Gesundheitssystem und erfordert neuartige Therapiekonzepte. Der Ansatz der Virulenzfaktorinhibition hat zum Ziel, die Schädlichkeit eines Pathogens zu verringern, ohne es dabei abzutöten und so die Entwicklung von Resistenzen zu verlangsamen. Das oppurtunistische Humanpathogen Pseudomonas aeruginosa (P. aeruginosa) produziert eine Vielzahl von Virulenzfaktoren, darunter das Phenazin Pyocyanin. Pyocyanin spielt unter anderem eine wichtige Rolle bei der Bildung von reaktiven Sauerstoffspezies und Biofilmen. Das Phenzinbiosyntheseenzym PhzB katalysiert die zweifache Kondensation eines Aminoketons zu einem Pyocyaninvorläufer. Zwar ist PhzB nicht essentiell für diesen Prozess, steigert die Effizienz in vivo jedoch deutlich. Es stellt daher eine attraktive Zielstruktur zur Entwicklung von Pyocyanininhibitoren dar. Umfassende Untersuchungen zur Entwicklung von PhzB-Inhibitoren mündeten bisher in Molekülen mit hohen Affinitäten für das isolierte Enzym aber unzureichender Pyocyaninreduktion im Zellmodell. Ho Sui et al. identifizierten den selektiven Estrogenrezeptormodulator Raloxifen in einem drug‑repurposing-Ansatz als möglichen Inhibitor von PhzB. Raloxifen reduzierte die Pyocyaninreduktion in P. aeruginosa und verlängerte das Überleben von C. elegans in einem Infektionsmodell. Ausgehend von der in vorherigen Arbeiten erhaltenen Kokristallstruktur von Raloxifen mit BcPhzB wurden in der vorliegenden Arbeit in einem strukturbasierten Ansatz Raloxifenanaloga entwickelt. Die erhaltenen Substanzen wurden mittels biophysikalischer, biochemischer und röntgenkristallographischer Methoden umfassend charakterisiert. Dabei wurden mittels isothermer nano differential scanning fluorimetry und isothermer Titrationskalorimetrie Affinitäten zum PhzB-Ortoholog aus B. cepacia im unteren mikromolaren Bereich ermittelt. Verglichen mit der Ausgangssubstanz Raloxifen zeigten die entwickelten PhzB‑Liganden eine signifikant stärkere Inhibition der Pyocyaninproduktion in P. aeruginosa PA14. Durch Substitution der Hydroxylgruppen des Benzo[b]thiophengrundkörpers wurde des Weiteren die Affinität gegenüber dem humanen Estrogenrezeptor gesenkt und so eine Strategie zur weiteren Verbesserung der Selektvität in zukünftigen Studien erarbeitet. Die zahlreichen erhaltenen Kokristallstrukturen der Liganden gaben Aufschluss über ihren Bindungsmodus und liefern Anhaltspunkte für das rationale Strukturdesign von weiteren Analoga.The increase in microbacterial resistance to antibiotics is a major burden for the global healthcare system and requires novel therapeutic concepts. The concept of virulence factor inhibition aims to reduce the harmfulness of a pathogen without killing it and thus slowing down the development of resistance. The oppurtunistic human pathogen Pseudomonas aeruginosa (P. aeruginosa) produces a variety of virulence factors, including the phenazine pyocyanin. Among other effects, pyocyanin plays an important role in the generation of reactive oxygen species and formation of biofilms. The phenazine biosynthesis enzyme PhzB catalyses the double condensation of an aminoketone into a pyocyanin precursor. Although PhzB is not essential for this process, it significantly increases the efficiency in vivo. It therefore represents an attractive target structure for the development of pyocyanin inhibitors. Extensive studies on the development of PhzB inhibitors have so far resulted in molecules with high affinities for the isolated enzyme but insufficient pyocyanin reduction in P. aeruginosa. Ho Sui et al. identified the selective estrogen receptor modulator raloxifene as a potential inhibitor of PhzB in a drug-repurposing approach. Raloxifene reduced pyocyanin reduction in P. aeruginosa and prolonged the survival of C. elegans in an infection model. Based on the cocrystal structure of raloxifene with BcPhzB obtained in previous work, raloxifene analogues were developed using a structure-based approach. The compounds were thoroughly characterised using biophysical, biochemical and X-ray crystallographic methods. Using isothermal nano differential scanning fluorimetry and isothermal titration calorimetry, affinities to the PhzB orthologue from B. cepacia were determined in the low micromolar range. Compared to the parent compound raloxifene, the developed PhzB ligands showed a significantly stronger inhibition of pyocyanin production in P. aeruginosa PA14. Furthermore, the affinity towards the human estrogen receptor was reduced by substituting the hydroxyl groups of the benzo[b]thiophene base scaffold, thus providing a strategy to further improve selectivity in future studies. The numerous cocrystal structures of the ligands obtained provided information about their binding mode and guide the rational structural design of further analogues

Target Mass Corrections for Polarized Structure Functions and New Sum Rules

The target mass corrections are calculated for all structure functions of neutral and charged current deep inelastic scattering in lowest order in the coupling constant. Representations of the correction to the twist--2 and twist--3 contributions are derived both in Mellin-$n$ and $x$-space. The impact of the target mass corrections on the general relations between the twist--2 and twist--3 parts of the structure functions is studied and three new relations between the twist--3 contributions are derived.Comment: 34 pages LATEX, 1 style fil

Split-ring resonator with interdigital Split electrodes as detector for liquid and ion chromatography

The analysis of food and drugs as well as the monitoring of chemical processes and bioreactors by high-performance liquid chromatography and ion chromatography requires universal, cost-effective, and sensitive detectors. Therefore, this work presents a split-ring resonator that detects changes in the electrical and dielectric properties of the eluate from liquid chromatography or ion chromatography by monitoring the amplitude of the transmitted signal using an envelope detector. The used split-ring resonator consists of a simple printed circuit board featuring two microstrip lines. One is formed to a ring with interdigital split electrodes. The interdigital split electrodes forming the sensitive area significantly enhance the sensitivity to changes in relative permittivity, dielectric losses and electrical conductivity of the eluate In addition, the split-ring resonator is a small, inexpensive and easy-to-use detector that uses several dielectric parameters simultaneously for the measurement. Furthermore, the split-ring resonator measures these parameters at a significantly lower frequency than optical detectors and therefore measures different changes in frequency-dependent permittivity. For demonstrating feasibility of a split-ring resonator as a detector for high-performance liquid chromatography and ion chromatography, various anion and cation standards, basic and acidic amino acids, sugars, as well as sugar alcohols were separated and detected. A conductivity detector for ion chromatography and a refractive index detector for high-performance liquid chromatography were used as reference detectors