Laser Excitation of the Th-229 Nucleus.

The 8.4 eV nuclear isomer state in Th-229 is resonantly excited in Th-doped CaF_{2} crystals using a tabletop tunable laser system. A resonance fluorescence signal is observed in two crystals with different Th-229 dopant concentrations, while it is absent in a control experiment using Th-232. The nuclear resonance for the Th^{4+} ions in Th:CaF_{2} is measured at the wavelength 148.3821(5) nm, frequency 2020.409(7) THz, and the fluorescence lifetime in the crystal is 630(15) s, corresponding to an isomer half-life of 1740(50) s for a nucleus isolated in vacuum. These results pave the way toward Th-229 nuclear laser spectroscopy and realizing optical nuclear clocks.

Structural modeling of protein-RNA complexes using crosslinking of segmentally isotope-labeled RNA and MS/MS.

Ribonucleoproteins (RNPs) are key regulators of cellular function. We established an efficient approach, crosslinking of segmentally isotope-labeled RNA and tandem mass spectrometry (CLIR-MS/MS), to localize protein-RNA interactions simultaneously at amino acid and nucleotide resolution. The approach was tested on polypyrimidine tract binding protein 1 and U1 small nuclear RNP. Our method provides distance restraints to support integrative atomic-scale structural modeling and to gain mechanistic insights into RNP-regulated processes.

The diagnosis and conservative treatment of a complex type 3 dens invaginatus using cone beam computed tomography (CBCT) and 3D plastic models.

AIM: To investigate the use of 3D plastic models, printed from cone beam computed tomography (CBCT) data, for accurate diagnosis and conservative treatment of a complex case of dens invaginatus. SUMMARY: A chronic apical abscess with a draining sinus tract was diagnosed during the treatment planning stage of orthodontic therapy. Radiographic examination revealed a large radiolucent area associated with an invaginated right maxillary central incisor, which was found to contain a vital pulp. The affected tooth was strategic in the dental arch. Conventional periapical radiographs provided only partial information about the invagination and its relationship with the main root canal and with the periapical tissues. A limited-volume CBCT scan of the maxilla did not show evidence of communication between the infected invagination and the pulp in the main root canal, which could explain the pulp vitality. A novel method was adopted to allow for instrumentation, disinfection and filling of the invagination, without compromising the vitality of the pulp in the complex root canal system. The CBCT data were used to produce precise 3D plastic models of the tooth. These models facilitated the treatment planning process and the trial of treatment approaches. This approach allowed the vitality of the pulp to be maintained in the complex root canal space of the main root canal whilst enabling the healing of the periapical tissues. KEY LEARNING POINTS: Even when extensive periapical pathosis is associated with a tooth with type III dens invaginatus, pulp sensibility tests should be performed. CBCT is a diagnostic tool that may allow for the management of such teeth with complex anatomy. 3D printed plastic models may be a valuable aid in the process of assessing and planning effective treatment modalities and practicing them ex vivo before actually performing the clinical procedure. Unconventional technological approaches may be required for detailed treatment planning of complex cases of dens invaginatus.

Necrosis-inducing proteins of Rhynchosporium commune, effectors in quantitative disease resistance.

The barley pathogen Rhynchosporium commune secretes necrosis-inducing proteins NIP1, NIP2, and NIP3. Expression analysis revealed that NIP1 transcripts appear to be present in fungal spores already, whereas NIP2 and NIP3 are synthesized after inoculation of host plants. To assess the contribution of the three effector proteins to disease development, deletion mutants were generated. The development of these fungal mutants on four barley cultivars was quantified in comparison with that of the parent wild-type strain and with two fungal strains failing to secrete an "active" NIP1 avirulence protein, using quantitative polymerase chain reaction as well as microscopic imaging after fungal green fluorescent protein tagging. The impact of the three deletions varied quantitatively depending on the host genotype, suggesting that the activities of the fungal effectors add up to produce stronger growth patterns and symptom development. Alternatively, recognition events of differing intensities may be converted into defense gene expression in a quantitative manner.

The natural history of the hyperthyrotropinemia of children born prematurely.

OBJECTIVE: Non-autoimmune hyperthyrotropinemia has been previously reported among children born prematurely. The aim of this study was to follow up their thyroid function, volume, and structure and to investigate the relationship with growth, IGF-I, lipid profile, and insulin sensitivity. METHODS: Seventy-two children born prematurely (33.2±2.2 weeks), 26 appropriate (AGA) and 46 small for gestational age (SGA), were evaluated at the age of 7.6±2.3 yr (time 1) and at the age of 11.4±2.3 yr (time 2). We also measured TSH, free T(3) (fT(3)), free T(4) (fT(4)), thyroperoxidase antibodies (TPO-Ab), thyroglobulin antibodies (TG-Ab), thyroid ultrasound, auxological parameters, lipid profile, glucose, and insulin level. RESULTS: In the AGA group TSH was similar in both times (2.7±1.0 vs 3.0±0.9 mU/l) and above the upper normal limit in 4 (15.4%) subjects at time 1 and in 6 (23.7%) subjects at time 2 (ns). In the SGA group, TSH was similar in both times (2.8±1.2 vs 2.5±1.0 mU/l) and above the upper normal limit in 11 (23.9%) subjects at time 1 and 5 (10.8%) subjects at time 2 (ns). fT(4) and fT(3) were always normal and TPO- and TG-Ab absent. Thyroid volume increased progressively, but significantly only in the AGA group (p=0.0005). The thyroid structure was always normal and there was no influence on the growth and the biochemical profile. CONCLUSIONS: Some ex-premature babies show a mild and variable thyroid dysfunction, which does not seem to evolve toward an overt thyroid dysfunction.

[Modern therapy of chronic myeloid leukemia: an example for paradigma shift in hemato-oncology]. / Moderne Therapie der chronischen [corrected] myeloischen Leukämie : Ein Beispiel für den Paradigmenwechsel in der Hämatoonkologie.

Chronic myeloid leukemia (CML) is exceptional amongst neoplasias since its underlying pathomechanism has been elucidated, and potent well tolerated targeted drugs, the tyrosine kinase inhibitors (TKI), are available for treatment. They convincingly improve prognosis while retaining good quality of life. Aims of therapy are complete remissions as well as prolongation of life and cure. Imatinib 400 mg per day is current standard therapy. There are hints for a better outcome with a higher initial imatinib dose or with combination therapy. Even after achievement of complete molecular response continuous therapy might be necessary in most cases. In case of imatinib intolerance or failure, the second generation TKI dasatinib and nilotinib and allogeneic stem cell transplantation are available. The use of second generation TKI as first line treatment might further improve prognosis. The therapeutic response should be regularly monitored according to international recommendations.

Superresolution Moiré mapping of particle plasmon modes.

The spontaneous emission rate of a fluorophore provides a direct probe of the photonic local density of states at the fluorophore position. Here we exploit this capability to map the plasmonic modes of gold nanoparticles by imaging the fluorescence intensity in combined regular arrays of identical gold and fluorophore-doped polymer nanoparticles. By varying the distance between gold and polymer particles across the array, the fluorophore emission generates an optical Moiré pattern corresponding to a magnified spatial map of the plasmonic mode, which can be directly imaged with an optical microscope. Our results are corroborated by supplementary theoretical model calculations.

Coupling dielectric waveguide modes to surface plasmon polaritons.

We study dielectric/metal thin film multilayers designed for the coupling of dielectric waveguide modes and surface plasmons. The coupling as identified in calculated dispersion relations for extended multilayers is confirmed by measured angle-resolved reflectance data. By lateral structuring of the multilayers the mutual coupling of dielectric and plasmonic modes is directly observed by fluorescence based microscopy. For a light wavelength of 514nm we find a coupling length of 15microm. Our results highlight the potential of hybrid dielectric/metal waveguides for integrating surface plasmon based photonic circuitry or sensing elements into conventional optical devices.

Dynamic nanoindentation testing: is there an influence on a material's hardness?

Modern nanoindentation devices are capable of dynamic experimentations, which allow us to exploit instrumented hardness tests extensively. Beside the assets of recording mechanical properties continuously over displacement, there are ongoing debates whether the superimposed force alters the material's hardness. We will show for a broad range of materials that significant hardness differences are noted between dynamic and static tests, even for large displacements. Those mainly result from a changing indentation strain-rate during the hold segment at peak load. This fact must be implicitly considered in studies using static indentation tests to guarantee comparability of obtained nanoindentation hardness values and derived quantities.

A meta-analytic review of brief guided self-help education for chronic pain.

Up to 30% of the population in Western countries suffer from chronic pain. The treatment of chronic pain causes medical and socioeconomic problems. Guided self-help (GSH) might be an effective supplementary treatment, however, the size of this effect is unclear. This meta-analysis quantifies the effect of GSH on chronic pain. A systematic literature search was conducted using PubMed, Cochrane, Psyndex, Psycinfo and Scopus. Studies that investigated GSH in chronic pain conditions (children and adults) were included. Disability, quality of life and pain severity were defined as main outcomes. We conducted random effects models to calculate standardized mean differences (SMDs). By applying mixed models and subgroup analyses, we examined the moderating effects of sample characteristics (age; pain region), GSH format (online; face-to-face contact) and study characteristics (study quality; control condition). We identified 16 eligible studies, including 739 subjects. Between-group analyses resulted in a medium, but heterogeneous effect size for pain severity (SMD = 0.51; CI95 : 0.21, 0.81). After excluding two samples suggesting small study bias, the effect on pain severity was small but homogeneous (SMD = 0.34; CI95 : 0.13, 0.54). We found a small effect size for disability (SMD = 0.30; CI95 : 0.10, 0.50). The pooled effect size for quality of life did not reach significance (SMD = 0.24; CI95 : -0.07, 0.54). We conclude that GSH has a small but robust effect on pain severity and disability in chronic pain patients. This applies to various GSH formats and patient populations. It seems reasonable to integrate GSH into clinical practice as a supplemental treatment option. WHAT DOES THIS REVIEW ADD?: The present meta-analytic review found small but robust effects of guided self-help interventions for the treatment of chronic pain.

Three dimensional sensitivity characterization of plasmonic nanorods for refractometric biosensors.

An experimental three dimensional characterization of the local refractive index sensitivity of plasmonic gold nanorods is performed by controlled apposition of lithographic nanostructures. We show up to seven times higher sensitivity values to local changes in the refractive index at the particle tip than center. In addition, successive deposition of defined nm-thin dielectric layers on nanorods covered with stripe masks allows us to study the sensitivity decrease normal to the particle surface separately for different particle sites. Clear trends to a stronger sensitivity decay at sites of higher local sensitivity are demonstrated experimentally and theoretically. Our sensitivity characterization provides an important tool to find the most suitable particle type and particle site for specific bio-sensing applications.

Solid-phase capture and release of arginine peptides by selective tagging and boronate affinity chromatography.

A method for the selection of arginine-containing peptides from a mixture by a solid phase capture and release technique is presented. The method is based on the covalent modification of the guanidine group of arginine with 2,3-butanedione and phenylboronic acid under alkaline conditions. Using polymeric materials with immobilised phenylboronic acid the arginine-peptides can be captured on a solid support while arginine-free peptides are not covalently bound and can be washed away. Finally, the arginine-peptides can be cleaved again from the boronic acid beads due to the reversibility of the reaction. The recovered peptides are then analysed by liquid chromatography-tandem mass spectrometry. The method was optimised with model peptides with regard to the non-specific binding of arginine-free peptides and quantitative cleavage of the label after the selection step. Using an adequate protocol, the applicability towards more complex samples was successfully tested with a tryptic digest of a mixture of three standard proteins.

Metal nanoparticle gratings: influence of dipolar particle interaction on the plasmon resonance

We probe the influence of grating effects on plasmon excitations in gold nanoparticles arranged in regular two-dimensional patterns. Samples produced by electron-beam lithography are investigated by femtosecond time-resolved and spectroscopic methods. We find a strong dependence of the plasmon lifetime and resonance wavelength on the grating constant.

Characterization of hematopoietic stem cells.

On the basis of density-separated mononuclear cells isolated from bone marrow, peripheral blood, and cord blood, we have repeatedly shown good correlation between two-color flow cytometric (FACS) CD34 analysis and colony formation in the clonogenic assay. We have analyzed the distributions of CD34 subpopulations in these three stem cell sources using patients' and donors' bone marrow biopsies (n = 196), cord blood samples from full-term deliveries (n = 14), and peripheral blood from patients mobilized by chemotherapy and/or cytokine treatment (n = 258). Irrespective of absolute cell counts, the mean (+/- SD) proportions of CD34+ cells were clearly higher in bone marrow (5.6 +/- 4.6% of mononuclear cells) than in peripheral blood (1.9 +/- 2.6) and cord blood (1.7 +/- 2.6). However, two-color FACS analyses revealed significant differences among these cell sources with regard to their distribution of CD34 subpopulations: B-cell progenitors coexpressing CD34 and CD19, at considerable concentrations of > 0.5%, were only found in bone marrow (mean 30 +/- 24.3% of CD34+ mononuclear cells, median 28.7%, minimum 0%, maximum 83.3%). In addition, CD34+ cells in S/G2M phase were never detected in peripheral blood or cord blood, but only in bone marrow at a concentration of 10-15% of CD34+ mononuclear cells. On the other hand, the proportions of relatively immature myeloid progenitors, as characterized by not expressing CD45RA and by higher clonogenic capacity, were significantly higher in cord blood (76.7 +/- 17.2) and peripheral blood (58.2 +/- 17.5) than in bone marrow (26.4 +/- 16.7). These data were confirmed by analysis of apheresis products and of progenitors positively selected from different cell sources, and they may explain why, in autologous transplantations of analogous amounts of CD34+ cells, peripheral blood is superior to bone marrow. We conclude from our results that if successful transplantation and timely recovery depend on the number of CD34+ cells transplanted, the mean amount of stem cells required is 1.4- (for myeloid cells) or 2.2-fold (for early myeloid cells) higher for bone marrow than for peripheral blood.

Determination of the metabolites of nitrofuran antibiotics in animal tissue by high-performance liquid chromatography-tandem mass spectrometry.

A LC-MS-MS method is presented to analyse simultaneously the metabolites of four nitrofuran antibacterial agents, furazolidone, furaltadone, nitrofurazone and nitrofurantoin in animal muscle tissue. Sample clean-up and analyte enrichment was performed by solid-phase extraction (SPE) with a polystyrene sorbent following combined hydrolysis of the protein-bound drug metabolites and derivatisation of the homogenised tissue with 2-nitrobenzaldehyde. Limits of detection of 0.5-5 ng g(-1) tissue and limits of determination of 2.5-10 ng g(-1) tissue were achieved using electrospray ionisation in positive mode. Analyte identification and quantification was performed according to EU guidelines, using multiple reaction monitoring (MRM) with one precursor ion and two product ions as identifiers. The use of an internal standard in combination with the simplified sample preparation led to a sensitive and reliable analysis method. The yield of the derivatisation reaction was between 66 and 74% and the recovery of SPE reached 92-105% for all values between 10 and 500 ng g(-1). The developed analytical protocol has been applied to contaminated tissue samples of furazolidone- and furaltadone-treated pigs and allowed unequivocal identification and quantification of the metabolites.

Salsolinol and norsalsolinol in human urine samples.

The tetrahydroisoquinoline alkaloids salsolinol and norsalsolinol were found in human urine samples in concentrations ranging from 0.1 to 29.5 ng/ml. Great interindividual variation was found in urine levels of these alkaloids in a collection of chronic alcoholics and in a group of nonalcoholics. Thus, levels of the individual alkaloids are insufficient markers for distinguishing between alcoholics and nonalcoholics. However, by using the concentration ratio of norsalsolinol and salsolinol, the so-called dopamine-aldehyde adduct ratio (DAAR), significant differences between alcoholics (median 1.3) and nonalcoholics (median 0.6) were detected. This concentration ratio could serve as a marker for the processor state of the dopaminergic system.

[Epidemiology of attempted suicide by drug overdose in Vienna]. / Beitrag zur Epidemiologie medikamentöser Suizidversuche in Wien.

We studied 361 Viennese patients (m = 111, f = 250) admitted to our observation ward after attempted suicide by drug ingestion over a two-year period. Age and sex distribution, social status, time of attempt, motives, and drugs used were documented, as well as the therapeutic management of the cases. The patients were divided into 4 age groups: 57 juveniles, 179 young adults, 80 middle-aged adults and 45 geriatric patients. These groups were compared with each other in manifold respects. Our analysis showed that the geriatric patients who had attempted suicide by drug ingestion differed from those of other groups insofar as there was a lack of exogenous influence with regard to motives and methods. They may represent a separate entity more akin to suicide than to attempted suicide. Vienna data on attempted suicide by drug ingestion did not differ markedly from international data.

Under-performance evaluation and rehabilitation strategy for waste stabilization ponds in Mexico.

Fourteen high altitude (> 2,500 m amsl) small Waste Stabilisation Pond systems (WSPs) commissioned during the last 12 years in the State of Mexico in Mexico, were built to a common 3-stage design. Each system is comprised of 2 parallel series of bio-digesters, anaerobic and facultative ponds. All fourteen WSP systems produce poor quality effluents, and eight studied in more detail did not meet any of the national standards for discharge to rivers or the standards required for reuse. The under-performance of these WSPs is underlined by the anaerobic condition of the upper reaches of the Lerma river which receives the sewage from the towns served by these treatment plants. Preliminary surveillance diagnostics identified fundamental operational problems in all eight WSP systems located in the upper Lerma catchment. The results of an intensive secondary diagnostic performance evaluation on one system were used to identify the reasons for under-performance. Under-performance was caused by under-design, hydraulic short-circuiting, adverse environmental conditions and poor operation and maintenance. A strategy for improvement of design and operation to meet national standards is presented.

[Ethanol-independent methanol elimination in chronic alcoholics]. / Ethanolunabhängige Methanolelimination bei chronischen Alkoholikern.

72% of a collective of chronic alcoholics (DSM-III-R, ICD 9), who were admitted under the influence of alcohol in order to undergo alcohol withdrawal, showed a serum methanol concentration (SMC) above 10 mg/l. This level is usually considered to be the one for the detection of regular alcohol consumption. The SMC values were considerably higher in cases where alcoholic beverages with a higher methanol content were consumed rather than the ones lower in methanol. In the majority of patients a decrease of the methanol concentration could only be detected once an individually varying limit concentration of ethanol (0-0.62 g/kg) was reached. There were, however, a few exceptions where the elimination of methanol independent from the ethanol concentration could be seen. Contrasting the general collective, these 'ethanol independent' methanol eliminators showed a much higher serum level of ethanol and methanol at the time of admission. As a sign of addiction, all patients showed increased beta 60 values for ethanol and preferred high proof beverages, which at the same time have high methanol contents.