Direct detection of the (229)Th nuclear clock transition.

Today's most precise time and frequency measurements are performed with optical atomic clocks. However, it has been proposed that they could potentially be outperformed by a nuclear clock, which employs a nuclear transition instead of an atomic shell transition. There is only one known nuclear state that could serve as a nuclear clock using currently available technology, namely, the isomeric first excited state of (229)Th (denoted (229m)Th). Here we report the direct detection of this nuclear state, which is further confirmation of the existence of the isomer and lays the foundation for precise studies of its decay parameters. On the basis of this direct detection, the isomeric energy is constrained to between 6.3 and 18.3 electronvolts, and the half-life is found to be longer than 60 seconds for (229m)Th(2+). More precise determinations appear to be within reach, and would pave the way to the development of a nuclear frequency standard.

Small-Footprint, Field-Deployable LC/MS System for On-Site Analysis of Per- and Polyfluoroalkyl Substances in Soil.

Per- and polyfluoroalkyl substances (PFASs) are emerging environmental pollutants of global concern. For rapid field site evaluation, there are very few sensitive, field-deployable analytical techniques. In this work, a portable lightweight capillary liquid chromatography (capLC) system was coupled with a small footprint portable mass spectrometer and configured for field-based applications. Further, an at-site ultrasound-assisted extraction (pUAE) methodology was developed and applied with a portable capLC/mass spectrometry (MS) system for on-site analysis of PFASs in real soil samples. The influential variables on the integration of capLC with MS and on the resolution and signal intensity of the capLC/MS setup were investigated. The important parameters affecting the efficiency of the pUAE method were also studied and optimized using the response surface methodology based on a central composite design. The mean recovery for 11 PFASs ranged between 70 and 110%, with relative standard deviations ranging from 3 to 12%. In-field method sensitivity for 12 PFASs ranged from 0.6 to 0.1 ng/g, with wide dynamic ranges (1-600 ng/g) and excellent linearities (R2 > 0.991). The in-field portable system was benchmarked against a commercial lab-based LC-tandem MS (MS/MS) system for the analysis of PFASs in real soil samples, with the results showing good agreement. When deployed to a field site, 12 PFASs were detected and identified in real soil samples at concentrations ranging from 8.1 ng/g (for perfluorooctanesulfonic acid) to 2935.0 ng/g (perfluorohexanesulfonic acid).

Miniature Multiwavelength Deep UV-LED-Based Absorption Detection System for Capillary LC.

A new miniature deep UV absorbance detector has been developed using low-cost and high-performance LEDs, which can be operated in both scanning (230 to 300 nm) and individual wavelength (240, 255, and 275 nm) detection modes. The detector is mostly composed of off-the-shelf components, such as LEDs, trifurcated fiber optic assembly, a capillary Z-type flow cell, and photodiodes. It has been characterized for use with a standard capillary LC system and was benchmarked against a standard variable wavelength capillary LC detector. The detector shows very low levels of stray light (<0.4%), utilization of up to 99.0% of the effective path length of the flow cell, a wide dynamic range (0.5 to 200 µg/mL for sulfamethazine, carbamazepine, and flavone), and low noise levels (at 300 µAU level). The detector was applied within a miniaturized LC system.

Radiation protection modelling for 2.5 Petawatt-laser production of ultrashort x-ray, proton and ion bunches: Monte Carlo model of the Munich CALA facility.

The 'Centre for Advanced Laser Applications' (CALA) is a new research institute for laser-based acceleration of electron beams for brilliant x-ray generation, laser-driven sub-nanosecond bunches of protons and heavy ions for biomedical applications like imaging and tumour therapy as well as for nuclear and high-field physics.The radiation sources emerging from experiments using the up to 2.5 petawatt laser pulses with 25 femtosecond duration will be mixed particle-species of high intensity, high energy and pulsed, thus posing new challenges compared to conventional radiation protection. Such worldwide pioneering laser experiments result in source characteristics that require careful a-priori radiation safety simulations.The FLUKA Monte-Carlo code was used to model the five CALA experimental caves, including the corridors, halls and air spaces surrounding the caves. Beams of electrons (<5 GeV), protons (<200 MeV),12C (<400MeV/u) and197Au (<10MeV/u) ions were simulated using spectra, divergences and bunch-charges based on expectations from recent scientific progress.Simulated dose rates locally can exceed 1.5 kSv h-1inside beam dumps. Vacuum pipes in the cave walls for laser transport and extraction channels for the generated x-rays result in small dose leakage to neighboring areas. Secondary neutrons contribute to most of the prompt dose rate outside caves into which the beam is delivered. This secondary radiation component causes non-negligible dose rates to occur behind walls to which large fluences of secondary particles are directed.By employing adequate beam dumps matched to beam-divergence, magnets, passive shielding and laser pulse repetition limits, average dose rates in- and outside the experimental building stay below design specifications (<0.5µSv h-1) for unclassified areas,<2.5µSv h-1for supervised areas,<7.5µSv h-1maximum local dose rate) and regulatory limits (<1mSv a-1for unclassified areas).

Compact capillary high performance liquid chromatography system for pharmaceutical on-line reaction monitoring.

Due to their size, conventional high performance liquid chromatographs (HPLCs) are difficult to place close to a reaction vessel within a pharmaceutical manufacturing or development site. Typically, long transfer lines are required to move sample from the reactor to the HPLC for analysis and high solvent usage is required. However, herein a compact and modular separation system has been developed to enable co-location of an HPLC with a small-scale reactor for reaction monitoring in the synthesis of active pharmaceutical ingredients. Using a framework based on capillary HPLC, a compact gradient separation system with a fully modular architecture is described. A custom miniature diode-array detector with a linear dynamic range (up to 1500 mAU at 210 nm) was integrated and evaluated for on-line reaction monitoring. In evaluating system suitability, average peak area %RSD of <3%, and an average retention time %RSD of <0.7%, were achieved. To demonstrate practical utility, the compact system was coupled directly to an on-line lab-scale flow through reactor for continuous reaction monitoring in the laboratory fume hood, where a study of the 3rd Bourne reaction was used to compare the performance of the compact system with a commercially available process HPLC instrument (Waters PATROL UPLC). Further, 33 off-line samples from a continuous crystallization reactor were analysed and it was found that the developed compact HPLC system showed equivalent quantitative performance to an Agilent 1290 Infinity II HPLC system.

A simplified approach to direct SPE-MS.

Microextraction by packed sorbent (MEPS) has been directly hyphenated with ESI-MS for the rapid screening of opiates and codeine metabolites in urine. This study introduces a novel format of MEPS that incorporates a two-way valve in the barrel of the syringe enabling the direction of liquid flow to be manipulated. Controlled directional flow (CDF) MEPS allows sharp, concentrated sample bands to be delivered directly to the MS in small volumes and effectively eliminates the need to optimize elution. The method optimization assessed the recovery, matrix effects, and the speed of infusion, all critical variables for optimum ESI performance. Matching extraction workflows demonstrated a reduction in carryover from 65% for conventional MEPS to only 1% for CDF MEPS. The recovery (<89% for 50 µL sample), matrix effects (<42%), linearity (r(2) > 0.99), and LODs (<5 ng/mL) were determined to demonstrate method performance. The optimized approach was employed for the screening of codeine metabolites in urine. The ion trace revealed sharp sample bands corresponding to the codeine metabolites. At-line MEPS-ESI-MS allowed both sample preparation and analysis to be completed in only 5 min facilitating high throughput and alleviating the burden of method development.

Small footprint liquid chromatography-mass spectrometry for pharmaceutical reaction monitoring and automated process analysis.

Liquid chromatography (LC) has broad applicability in the pharmaceutical industry, from the early stages of drug discovery to reaction monitoring and process control. However, small footprint, truly portable LC systems have not yet been demonstrated and fully evaluated practically for on-line, in-line or at-line pharmaceutical analysis. Herein, a portable, briefcase-sized capillary LC fitted with a miniature multi-deep UV-LED detector has been developed and interfaced with a portable mass spectrometer for on-site pharmaceutical analysis. With this configuration, the combined small footprint portable LC-UV/MS system was utilized for the determination of small molecule pharmaceuticals and reaction monitoring. The LC-UV/MS system was interfaced directly with a process sample cart and applied to automated pharmaceutical analysis, as well as also being benchmarked against a commercial process UPLC system (Waters PATROL system). The portable system gave low detection limits (∼3 ppb), a wide dynamic range (up to 200 ppm) and was used to confirm the identity of reaction impurities and for studying the kinetics of synthesis. The developed platform showed robust performance for automated process analysis, with less than 5.0% relative standard deviation (RSD) on sample-to-sample reproducibility, and less than 2% carryover between samples. The system has been shown to significantly increase throughput by providing near real-time analysis and to improve understanding of synthetic processes.

Concept and performance evaluation of two 3 GHz buncher units optimizing the dose rate of a novel preclinical proton minibeam irradiation facility.

To demonstrate the large potential of proton minibeam radiotherapy (pMBRT) as a new method to treat tumor diseases, a preclinical proton minibeam radiation facility was designed. It is based on a tandem Van-de-Graaff accelerator providing a 16 MeV proton beam and a 3 GHz linac post-accelerator (designs: AVO-ADAM S.A, Geneva, Switzerland and ENEA, Frascati, Italy). To enhance the transmission of the tandem beam through the post-accelerator by a factor of 3, two drift tube buncher units were designed and constructed: A brazed 5-gap structure (adapted SCDTL tank of the TOP-IMPLART project (ENEA)) and a non-brazed low budget 4-gap structure. Both are made of copper. The performance of the two differently manufactured units was evaluated using a 16 MeV tandem accelerator beam and a Q3D magnetic spectrograph. Both buncher units achieve the required summed voltage amplitude of 42 kV and amplitude stability at a power feed of less than 800 W.

Helicobacter pylori modulates the T helper cell 1/T helper cell 2 balance through phase-variable interaction between lipopolysaccharide and DC-SIGN.

The human gastric pathogen Helicobacter pylori spontaneously switches lipopolysaccharide (LPS) Lewis (Le) antigens on and off (phase-variable expression), but the biological significance of this is unclear. Here, we report that Le+ H. pylori variants are able to bind to the C-type lectin DC-SIGN and present on gastric dendritic cells (DCs), and demonstrate that this interaction blocks T helper cell (Th)1 development. In contrast, Le- variants escape binding to DCs and induce a strong Th1 cell response. In addition, in gastric biopsies challenged ex vivo with Le+ variants that bind DC-SIGN, interleukin 6 production is decreased, indicative of increased immune suppression. Our data indicate a role for LPS phase variation and Le antigen expression by H. pylori in suppressing immune responses through DC-SIGN.

Development of polydimethylsiloxane-microdiamond composite materials for application as sorptive devices.

The development and application of non-porous and porous sorptive rods, comprised of polydimethylsiloxane-microdiamond (PDMS-MD) composites, is reported. The PDMS-MD composites were made porous using inorganic salt (NaCl and NaHCO3) particles as dissolvable templates. Materials with pore size of ~40 µm down to ~5 µm were produced. The advantages of incorporating up to ~60%microdiamond (2-4 µm) into PDMS included: (1) significant increase in the density, which saw the rods sink within the aqueous sample without addition of secondary metal or glass materials, (2) significant improvement in mechanical stability (the porous composite rods could be thermally treated multiple times before application, unlike porous PDMS), (3) increased thermal stability up to 450-500 °C with only 6% weight loss of volatile components, and (4) higher thermal conductivity, estimated to be 108% higher than for PDMS. The PDMS-MD investigated as a sorbent for extraction, followed by liquid desorption and GC-FID analysis. Recovery of the sorbent for test solutes, isoamyl acetate, ethyl hexanoate, ethyl octanoate, ethyl decanoate, and phenethyl acetate, was found to range from ~87% to >100, with RSD of 2.10-12.50% in synthetic wine samples. Non-porous composite rods provided similar % recoveries to a commercial sorptive device (PDMS Twister), whereas porous rods showed improved % recovery for most of the test solutes (>10-20%) when applied under similar conditions. The limits of detection (LOD) for the above solutes within the developed method ranged from 0.60 to 27.30 µg L-1). Application of the PDMS-MD-LD-GC-FID method to white wine samples demonstrated how the PDMS-MD composite material can be applied as a robust and an efficient sorptive phase for trace chemical analysis.

Ultraviolet absorbance detector based on a high output power 235 nm surface mounted device-type light-emitting diode.

A new miniaturised capillary flow-through deep-UV absorbance detector has been developed using a microscale surface mounted device- type light-emitting diode (LED) (Crystal IS OPTAN 3535-series), emitting at 235 nm and with a half-height band width of 12 nm, and a high-sensitivity Z-shaped flow-cell. Compared with a previously reported TO-39 ball lens LEDs emitting at 235 nm, the new generation LED produced a 20-fold higher optical output and delivered up to 35 times increase in external quantum efficiency (EQE). The Z-cell was based on a reflective rectangular optical path with cross-sectional dimensions of 100 × 100 µm and a physical optical pathlength of 1.2 mm. Inclusion of UV transparent fused-silica ball lenses, between the SMD and the Z-cell, improved light transmission by a factor of 9 and improved the detector signal-to-noise ratio by a factor of 2.2, at the same input current. The detector was housed within an Al-housing fitted with a cooling fan and demonstrated excellent linearity with stray light down to 0.06%, and an effective pathlength of 1.1 mm (92% of nominal pathlength). The resultant detector was fitted successfully into a briefcase-sized portable capillary HPLC system, and practically demonstrated with the detection of a mixture of 13 test compounds at the sub-mg L-1 level in <5 min using gradient elution.

Modular, cost-effective, and portable capillary gradient liquid chromatography system for on-site analysis.

This work demonstrates the development of a compact, modular, cost-effective separation system configured to address a specific separation problem. The principles of the separation are based on gradient capillary liquid chromatography where the system consists of precision stepper motor-driven portable syringe pumps with interchangeable glass syringes (100 µL to 1000 µL). Excellent flow-rate precision of < 1% RSD was achieved with typical flow-rates ranging from 1 µL/min to 100 µL/min, which was ideal for capillary columns. A variable external loop volume and electrically actuated miniature injection valve was used for sample introduction. Detection was based upon a commercial Z-type UV absorbance flow-cell housed within a custom-built cooling enclosure (40 mm x 40 mm) which also contained a UV-LED light-source and a photodiode. System and chromatographic performance was evaluated using linear gradient elution, with day to day repeatability of <1.5% RSD (n = 6) for peak area, and < 0.4% RSD (n = 6) for retention time, for the separation of a 5 component mixture using a 50 mm X 530 µm ID C18 3 µm particle capillary column. The system can run any commercial or in-house packed columns from 50 mm to 100 mm length with IDs ranging from 200 to 700 µm. The developed portable system was operated using custom-built windows-based chromatography software, complete with data acquisition and system control.

Phantom of the forest or successful citizen? Analysing how Northern Goshawks (Accipiter gentilis) cope with the urban environment.

By 2040, roughly two-thirds of humanity are expected to live in urban areas. As cities expand, humans irreversibly transform natural ecosystems, creating both opportunities and challenges for wildlife. Here, we investigate how the Northern Goshawk (Accipiter gentilis) is adjusting to urban environments. We measured a variety of behavioural and ecological parameters in three urban and four rural study sites. City life appeared related to all parameters we measured. Urban female goshawks were overall 21.7 (CI95% 5.13-130) times more likely to defend their nestlings from humans than rural females. Urban goshawks were 3.64 (CI95% 2.05-6.66) times more likely to feed on pigeons and had diets exhibiting lower overall species richness and diversity. Urban females laid eggs 12.5 (CI95% 7.12-17.4) days earlier than rural individuals and were 2.22 (CI95% 0.984-4.73) times more likely to produce a brood of more than three nestlings. Nonetheless, urban goshawks suffered more from infections with the parasite Trichomonas gallinae, which was the second most common cause of mortality (14.6%), after collisions with windows (33.1%). In conclusion, although city life is associated with significant risks, goshawks appear to thrive in some urban environments, most likely as a result of high local availability of profitable pigeon prey. We conclude that the Northern Goshawk can be classified as an urban exploiter in parts of its distribution.

Host Lewis phenotype-dependent Helicobacter pylori Lewis antigen expression in rhesus monkeys.

Both human and H. pylori populations are polymorphic for the expression of Lewis antigens. Using an experimental H. pylori challenge of rhesus monkeys of differing Lewis phenotypes, we aimed to determine whether H. pylori populations adapt their Lewis phenotypes to those of their hosts. After inoculation of four monkeys with a mixture of seven strains identified by RAPD-polymerase chain reaction, H. pylori Lewis expression was followed in 86 isolates obtained over 40 wk. Host Lewis(a/b) secretion status was characterized by immunological assays. Fingerprints of the predominating strain (J166) were identical in all four animals after 40 wk, but its Lewis phenotype had substantial variability in individual hosts. At 40 wk, J166 populations from two Lewis(a-b+) animals predominantly expressed Lewis(y). In contrast, J166 populations had switched to a Lewis(x) dominant phenotype in the two Lewis(a+b-) animals; a frame shift in futC, regulating conversion of Lewis(x) to Lewis(y), accounted for the phenotypic switch. The results indicate that individual cells in H. pylori populations can change Lewis phenotypes during long-term colonization of natural hosts to resemble those of their hosts, providing evidence for host selection for bacterial phenotypes.

[Dyspepsia, Ulcer Disease ­ Helicobacter pylori, Gastroesophageal Reflux Disease]. / Dyspepsie, Ulkuserkrankung - Helicobacter pylori, Refluxerkrankung.

Prevalence of H. pylori (HP) is declining, whereas reflux disease and the proportion of non-steroidal antiinflammatory drugs (NSAR) to HP-induced ulcers increase. Eradication heals HP-ulcer disease, interrupts cancerous progression and can improve dyspeptic symptoms. NSAR-ulcers heal under proton pump inhibitor (PPI) therapy but tend to recur after reexposition. Anticoagulants and antiplatlet agents increase the risk additionally. PPI reduces NSAR-ulcer recurrence. Reflux patients with severe inflammation and complications often need long-term therapy. Barrett's esophagus patients are at risk of esophageal adenocarcinoma.

Different Pathophysiology of Gastritis in East and West? A Western Perspective.

BACKGROUND: Gastritis results from multifactorial gastric mucosal injury. Helicobacter pylori (Hp) is the main cause, and associated diseases have typical underlying patterns of gastritis. Gastric ulcer and gastric cancer (GC) develop from chronic atrophic corpus gastritis (CAG) which therefore represents the most important pattern. GC incidences in East Asia are substantially higher than elsewhere, and this should be also reflected by higher prevalences of CAG and characteristic differences in pathophysiology compared to the West. SUMMARY: The few available comparative studies of gastritis in Eastern and Western patients are summarized. The main pathogenic factors of gastritis are discussed together with their limitations to explain local differences in disease outcome. Emphasis was put to also include less well-established pathogenic host and environmental factors of possible impact. CONCLUSIONS: CAG is more prevalent in East Asian areas with high GC incidences than the West. Geographic heterogeneity of associated diseases is due to differences in Hp prevalence and virulence as well as modulating host and environmental factors. The following may contribute to the higher burden of CAG in the East: ABD type of CagA with vacA s1 and babA2 alleles of Hp, host Lewis(b) expression in sej/sej nonsecretors, H. heilmannii, low parietal cell mass, high sodium and nitrate intake, preferences in vegetable and fruit consumption, cigarette smoking, air pollution, alcohol. Conversely, green tea, nonfermented soy products and rice may confer protective effects. Hp is on the decline, but also in a world cleared from this bacterium, differences in host genetics will continue to modify gastric disease outcome together with maintained customs as part of cultural diversity.

Characterization of large surface area polymer monoliths and their utility for rapid, selective solid phase extraction for improved sample clean up.

While polymer monoliths are widely described for solid phase extraction (SPE), appropriate characterization is rarely provided to unravel the links between physical characteristics and observed advantages and disadvantages. Two known approaches to fabricate large surface area polymer monoliths with a bimodal pore structure were investigated. The first incorporated a high percentage of divinyl benzene (PDVB) and the second explored hypercrosslinking of pre-formed monoliths. Adsorption of probe analytes; anisole, benzoic acid, cinnamic acid, ibuprofen and cortisone were investigated using frontal analysis and the SPE performance was compared with particulate adsorbents. Frontal analysis of anisole described maximum adsorption capacities of 164mgg(-1) and 298mgg(-1) for hypercrosslinked and PDVB adsorbents, respectively. The solvated state specific surface area was calculated to be 341 and 518m(2)g(-1) respectively. BET revealed a hypercrosslinked surface area of 817m(2)g(-1), 2.5 times greater than in the solvated state. The PDVB BET surface area was 531m(2)g(-1), similar to the solvated state. Micropores of 1nm provided the enhanced surface area for hypercrosslinked adsorbents. PDVB displayed a pore size distribution of 1-6nm. Frontal analysis demonstrated the micropores present size exclusion for the larger probes. Recovery of anisole was determined by SPE using 0.4 and 1.0mLmin(-1). Recovery for PDVB remained constant at 90%±0.103 regardless of the extraction flow rate suggesting extraction performance is independent of flow rate. A more efficient sample purification of saccharin in urine was yielded by PDVB due to selective permeation of the small pores.

Coagulase-negative staphylococci: clinical, microbiological and molecular features to predict true bacteraemia.

Coagulase-negative staphylococci (CNS) are frequently isolated from blood cultures, where they may be only a contaminant or the cause of bacteraemia. Determining whether an isolate of CNS represents a true CNS bacteraemia is difficult, and there is no single criterion with sufficient specificity. The aim of this study was to assess those clinical, microbiological, pathogenic and genotypic features that characterize true CNS bacteraemia. Twenty patients having two or more blood cultures positive for CNS and 20 patients with only one positive blood culture were studied. Significant bacteraemia was defined according to clinical and laboratory criteria. Incubation time for blood cultures to become positive, macroscopic appearance of colonies, species determination, biotype, susceptibility to antimicrobials, PFGE pattern and adherence capacity were all studied. Clinical bacteraemia was present in 16/20 patients with two or more positive blood cultures and in 2/20 patients with only one positive blood culture. A significant difference was seen in the median time to positivity between the 18 clinical bacteraemias and 22 contaminations (23.6 versus 29.2 h; P = 0.04, Wilcoxon). There was also a significant difference between the two groups in the median absorbance of the slime test (1.36 versus 0.58; P = 0.005). All significant bacteraemias with two or more positive blood cultures had the same species identified, the same antimicrobial susceptibility pattern and the same PFGE pattern. In two patients with true bacteraemia with only one positive blood culture, the incubation time for the culture to turn positive was <24 h and the slime production absorbance was >2.5. The most useful parameters for the diagnosis of true CNS bacteraemia for patients with two positive blood cultures were incubation time until positive, species identification, antimicrobial susceptibility pattern, slime production and PFGE pattern. For patients with only one blood culture positive for CNS, the useful parameters for prediction of true bacteraemia were incubation time until positive and slime production, both of which are simple, low-cost tests.

Negative ion graphitised carbon nano-liquid chromatography/mass spectrometry increases sensitivity for glycoprotein oligosaccharide analysis.

Negative ion nano-liquid chromatography/mass spectrometry (nano-LC/MS) and tandem mass spectrometry (nano-LC/MS(2)), using graphitised carbon as separating medium, were explored for analysing neutral and acidic O-linked and N-linked oligosaccharide alditols. Compared to the sensitivity of capillary LC/MS (flow rate of 6 microL/min) coupled with a conventional electrospray ionisation source, the nano-LC/MS (flow rate of 0.6 microL/min) with a nanoflow ion source was shown to increase the sensitivity ten-fold with a detection limit in the low-femtomole range. The absolute signals for the [M-nH](n-) ions of the oligosaccharides were increased 100-fold, enabling accumulation of high-quality fragmentation data in MS(2) mode, in which detection of low abundant sequence ions is necessary for characterisation of highly sialylated N-linked oligosaccharides. Oligosaccharides with high numbers of sialic acid residues gave dominant fragments arising from the loss of sialic acid, and less abundant fragments from cleavage of other glycosidic bonds. Enzymatic off-line desialylation of oligosaccharides in the low-femtomole range prior to MS(2) analysis was shown to increase the quality of the spectra. Automated glycofragment mass fingerprinting using the GlycosidIQ software confirmed the oligosaccharide sequence for both neutral desialylated as well as sialylated structures. Furthermore, the use of graphitised carbon nano-LC/MS enabled the detection of four sialylated O-linked oligosaccharides on membrane proteins from ovarian tissue (5 microg of total amount of protein).