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.

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.

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.

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.

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.

[The ICF in use: testing of a new concept in four clinics]. / Praktische Nutzung der ICF: Erprobung eines neuen Ansatzes in vier Kliniken.

The International Classification of Functioning, Disability and Health (ICF) consists of more than 1 400 items. Due to its size and complexity, using the ICF is hardly feasible in practice. Moreover, the severity of problems is given only on a five-point scale (qualifiers), which seems too insensitive for measurement of changes. Thus, in cooperation with four rehabilitation hospitals, Jacobi, Urban & Kaluscha have identified 148 relevant items for musculoskeletal diseases. For easier usage we assigned mnemonic three letter codes to these items, e. g. WAL for the item "Walking" (ICF d450). Then the physician assigns those few items which he and/or the patient consider most important. The severity of the problem is judged on a scale from 0 (no restriction) to 100 (maximum restriction) for each item. By drawing a bar on the scale the physician gives an interval instead of just a single point (fuzzy judgement). The centre of the interval represents the severity of the problem and the width represents the uncertainty of judgement, e. g. when there is no gold standard for measurement or when the problem varies with time. As both the assignment of descriptors from an item pool and the fuzzy judgements are a new approach to medical documentation, we carried out this pilot study to examine acceptance and feasibility of the approach. In the pilot study, 264 in-patients in four rehabilitation clinics have been included. 138 (94%) of the 148 descriptors in the item pool have been used. Altogether there were 1,764 single judgements. On average six descriptors per patient have been assigned, giving an efficient and precise individual documentation. This is an advantage of the documentation principle called combination of terms compared to the principle of classification. In contrast to the ICF core sets patients may get individual sets of descriptors as appropriate. On discharge, the judgements were about 25 points better compared to admission. During treatment the fluctuations of disorders decreased and the certainty of the judgements increased, resulting in reduction of interval width of 2.8 points. The feedback of the rehabilitation clinics involved showed good acceptance and feasibility. Our data can easily be mapped into the ICF. In addition to ICF core sets, our approach could facilitate the use of the ICF in practical settings.

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.

A phase II study of capecitabine and irinotecan in combination with concurrent pelvic radiotherapy (CapIri-RT) as neoadjuvant treatment of locally advanced rectal cancer.

We sought to evaluate the efficacy and safety data of a combination regimen using weekly irinotecan in combination with capecitabine and concurrent radiotherapy (CapIri-RT) as neoadjuvant treatment in rectal cancer in a phase-II trial. Patients with rectal cancer clinical stages T3/4 Nx or N+ were recruited to receive irinotecan (50 mg m(-2) weekly) and capecitabine (500 mg m(-2) bid days 1-38) with a concurrent RT dose of 50.4 Gy. Surgery was scheduled 4-6 weeks after the completion of chemoradiation. A total of 36 patients (median age 62 years; m/f: 27:9) including three patients with local recurrence were enclosed onto the trial. The median distance of the tumour from the anal verge was 5 cm. The main toxicity observed was (NCI-CTC grades 1/2/3/4 (n)): Anaemia 23/9/-/-; leucocytopenia 12/7/7/2, diarrhoea 13/15/4/-, nausea/vomiting 9/10/2/-, and increased activity of transaminases 3/3/1/-. One patient had a reversible episode of ventricular fibrillation during chemoradiation, most probably caused by capecitabine. The relative dose intensity was (median/mean (%)): irinotecan 95/91, capecitabine 100/92). Thirty-four patients underwent surgery (anterior resection n=25; abdomino-perineal resection n=6; Hartmann's procedure n=3). R0-resection was accomplished in all patients. Two patients died in the postoperative course from septic complications. Pathological complete remission was observed in five out of 34 resected patients (15%), and nine patients showed microfoci of residual tumour (26%). After a median follow-up of 28 months one patient had developed a local recurrence, and five patients distant metastases. Three-year overall survival for all patients with surgery (excluding three patients treated for local relapse or with primary metastatic disease) was 80%. In summary, preoperative chemoradiation with CapIri-RT exhibits promising efficacy whereas showing managable toxicity. The local recurrence and distant failure rates observed after a median 28 months are low compared with standard 5-fluorouracil based therapy.

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.

Imaging surface plasmon of gold nanoparticle arrays by far-field Raman scattering.

We present Raman spectra and Raman images of the methylene blue molecule adsorbed as a single layer on gold nanoparticles regularly arranged in periodic arrays. Spectra and images are recorded in the same spatial and spectral regions using an excitation under total internal reflection. Images of the Raman scattering appear as spots of circular shape located at the particle positions with size defined by the diffraction limit. It appears that all excited particles contribute equally to the Raman signal if the Gaussian intensity distribution of the laser beam is taken into account. These results demonstrate that Raman scattering can be a useful technique to study plasmon properties.

Detection of fluorescently labeled microparticles in blood.

BACKGROUND: A microsphere-based detoxification system is an adsorption system, whereby microadsorbent particles having diameters of 1-20 microm circulate in an extracorporeal filtrate circle. A thin-wall hollow-fiber membrane filter separates the microparticle-plasma suspension from the bloodstream. For patient safety, it is necessary to have a means to detect membrane ruptures that could lead to a release of microparticles into the patient's bloodstream. METHODS: An optical detection system was developed to monitor the venous bloodstream for the presence of microparticles from the filtrate circuit. For detection purposes, cellulose microspheres, both ferromagnetic and fluorescence labeled, were included with the microsphere adsorbant particles. In the case of a membrane rupture, the labeled particles would also be released into the bloodstream. By illuminating a small volume of blood with an excitation wavelength (590 nm) of the fluorescence marker, the particles can be detected by their emission light at 620 nm. The detector sensitivity is increased by collecting the ferromagnetic and fluorescently labeled microparticles using a magnetic trap. The efficiency of magnetic trap arrangements was tested by adjusting the magnet placements. RESULTS: In vitro experiments were performed by pumping whole blood and labeled microparticles through the fluorescence detector. The efficiency of a magnetic trap arrangement was determined. With an optimal trap setup, 5-10 microl of labeled microparticles can be clearly detected in streaming whole blood. CONCLUSION: An easy to handle microparticle detector was developed, ready for use in particle based blood detoxification systems. The microparticle detection system fulfills the medical and technical requirements to bring the MDS into clinical tests.

Surface enhanced Raman scattering arising from multipolar plasmon excitation.

Visible and near infrared extinction spectra of gold nanorod regular arrays exhibit several bands assigned to high multipolar order plasmon resonances. These up to ninth order multipolar resonances generate surface enhanced Raman scattering spectra with typically 5 x 10(4) enhancement which is of similar magnitude as those obtained for dipolar excitations.

Surface plasmon polariton-based optical beam profiler.

We describe a surface plasmon polariton- (SPP-) based device for measuring the intensity distribution of strongly focused light beams. A gold thin film configured as a sharp step is positioned in the focal region of a light beam, converting light into SPPs. The SPPs emit directional leakage radiation into the glass substrate beneath the thin film. The intensity of the leakage radiation is proportional to the intensity of the incident local light at the position of the step, allowing us to reconstruct the optical field profile by scanning the thin film's edge through the focal region.

Gold particle interaction in regular arrays probed by surface enhanced Raman scattering.

Lithographically designed two-dimensional arrays consisting of gold nanoparticles deposited on a smooth gold film are used as substrate to examine the SERS effect of the trans-1,2-bis (4-pyridyl) ethylene molecule. These arrays display two plasmon bands instead of the single one observed for the same arrays of particles but deposited on indium tin oxide coated glass. Laser excitation within the short wavelength band does not bring about any SERS spectrum, while excitation within the long wavelength band yields SERS spectra with a gain per molecule rising up to 10(8). The simultaneous investigation of extinction and Raman spectra of arrays exhibiting various topography parameters enables us to suggest an interpretation for both the occurrence of the two plasmon resonances and for the high Raman enhancement. We suggest to assign the short wavelength band to a plasmon wave propagating at the gold glass interface and the long wavelength one to an air/gold surface plasmon mode modified by particle-particle interaction.