This study related clinical effects to daily doses and serum concentrations of ziprasidone by retrospective analysis of data from a therapeutic drug monitoring (TDM) survey established for patients treated with the new antipsychotic drug. In the total sample of 463 patients ziprasidone doses ranged between 20 and 320 mg/d and correlated significantly (r2 = 0.093, P < 0.01) with serum concentrations. The latter were highly variable within and between individual patients (between patients median 67 ng/ml, 25–75th percentile 40–103 ng/ml). Pharmacokinetic interactions with comedication played a minor role. According to the clinical global impressions (CGI) scale most of the 348 patients who were under antipsychotic monotherapy with ziprasidone were either much or very much improved (43.3 and 17.3%, respectively). The previously proposed therapeutic range of 50–130 ng/ml ziprasidone in serum or plasma, which can in effect be used interchangeable, was confirmed. In patients who were at least much improved and defined as “responders” mean serum concentrations of ziprasidone were 80 ng/ml and 78 ng/ml in patients who did not reach this improvement score. In patients with serum levels above or below 50 ng/ml, the number of responders was 66 or 63%, respectively. The difference between the two groups was not significant (P = 0.375), and improvement or side effects did not correlate significantly (P > 0.05) with doses or serum levels. It is concluded that TDM of ziprasidone may be useful for treatment optimization because of highly variable serum concentrations resulting under therapeutically recommended doses of the drug.

The interaction of two laser-induced bubbles in bulk water is investigated. The strength and direction of the emerging liquid jets can be controlled by adjusting the relative bubble positions, the time difference between bubble generation, and the laser pulse energies determining the bubble sizes. Experimental and numerical studies are performed for millimetre-sized bubble pairs. Taking bubbles of equal energy, a maximum jet velocity is found for close anti-phase bubbles, i.e. when the second bubble is produced at the maximum volume of the first one and the bubble walls are almost touching and not merging. Under these conditions, one bubble produces a fast jet with a peak velocity of about $150~\text{m}~\text{s}^{-1}$ that reaches a distance into the surrounding liquid of at least three times the maximum bubble radius. Collapse of the other bubble results in a slow jet of large mass that rapidly converts into a ring vortex. Correspondingly, the interaction with adjacent structures is dominated either by localized jet impact or by shear stresses extending over a larger area. Furthermore, interactions between micrometre-sized bubble pairs are investigated numerically to understand and predict how the effects of the physical parameters on bubble dynamics would change when the bubbles become smaller. The results are discussed with respect to micropumping and opto-injection.

Today’s conversion of solar energy into electricity is based on silicon, which is pure, eventually crystalline, and its most efficient transitions are away from solar radiation maximum. The continuous search of efficient photovoltaic materials has recently focused on lead-halide organic-inorganic perovskite materials due to the very flexible, sustainable, and forgiving procedure of their fabrication, which is successful even if the concentrations of precursors, and temperature regimes deviate from optimal values. In addition to simple fabrication, this class of materials provides impressively high efficiency of photovoltaic (PV) cells. Attention to these materials helps to understand the mechanisms of their high efficiencies and to identify other materials with same type of properties. This work presents computational analysis of photo-induced processes in perovskite materials at ambient temperatures.

The University of Bern has set up the new Laboratory for the Analysis of Radiocarbon with AMS (LARA) equipped with an accelerator mass spectrometer (AMS) MICADAS (MIni CArbon Dating System) to continue its long history of 14C analysis based on conventional counting. The new laboratory is designated to provide routine 14C dating for archaeology, climate research, and other disciplines at the University of Bern and to develop new analytical systems coupled to the gas ion source for 14C analysis of specific compounds or compound classes with specific physical properties. Measurements of reference standards and wood samples dated by dendrochronology demonstrate the quality of the 14C analyses performed at the new laboratory.

We conducted in-situ high-temperature neutron and X-ray diffraction studies on tetragonal PbTiO3. Using a combination of Rietveld analysis and Maximum Entropy Method, the nuclear and charge density distributions were determined as a function of temperature up to 460 °C. The ionic states obtained from charge density distributions reveal that the covalency of Pb–O2 bonds gradually weakens with increasing temperature. The spontaneous polarizations calculated from the contributions of ionic state, ionic displacement, and nuclear polarization, are in good agreement with the experimental measurements. This method provides an effective approach to determine spontaneous polarizations in multiferroics with high-current leakage and low resistance.

In this paper we describe the capabilities for texture measurements of the new neutron time-of-flight diffractometer HIPPO at the Los Alamos Neutron Science Center. The orientation distribution function (ODF) is extracted from multiple neutron time-of-flight histograms using the full-pattern analysis first described by Rietveld. Both, the well-established description of the ODF using spherical harmonics functions and the WIMV method, more recently introduced for the analysis of time-of-flight data, are available to routinely derive the ODF from HIPPO data. At ambient conditions, total count time of less than one hour is ample to collect sufficient data for texture analysis in most cases. The large sample throughput for texture measurements at ambient conditions possible with HIPPO requires a robust and reliable, semi-automated data analysis. HIPPO’s unique capabilities to measure large quantities of ambient condition samples and to measure texture at temperature and uni-axial stress are described. Examples for all types of texture measurements are given

Background: Research on group therapy indicates that various dimensions of the helpful relationship qualities (cohesion, climate, empathy, alliance) are associated with outcome. However, the use of a wide variety of empirical scales makes comparisons between studies as well as generalizations somewhat difficult. Although a generic, trans-theoretical measure such as the Group Climate Questionnaire-Short Form (GCQ-S; MacKenzie, 1983) is available and applicable to most treatment conditions, it has never been tested with cognitive-behavioural group therapy. Aims: To investigate perceived dimensions of group climate (engagement, avoidance and conflict) as predictors of long-term (1 year) follow-up in a manualized, structured time-limited cognitive-behavioural group therapy (CBGT) for out-patients with comorbid psychiatric disorders. Methods: Data from 27 patients were analysed using hierarchical multiple regression analyses. Outcome measures used were general symptomatic complaints (SCL-90-R), interpersonal problems (IIP-64), specific mood- and anxiety symptoms (BDI; BAI) and early maladaptive schemas (YSQ). After controlling for scores on the relevant dependent variables at both intake and treatment termination, dimensions of group climate measured close to termination were entered as predictors in separate analyses. Results: Higher ratings of engagement were associated with reduced scores on all outcome measures at follow-up, except for anxiety symptoms (BAI). Higher ratings of avoidance were associated with lower anxiety symptoms at follow up, whereas ratings of conflict were unrelated to all follow-up scores. Conclusions: The results provide partial support for the use of the GCQ-S as a predictor of long-term follow-up in CBGT, and highlights perceived engagement as the most important dimension. Clinical implications are discussed.

The crystalline quality of bonded Silicon-On-Insulator (SOI) wafers were examined by spectroscopic ellipsometry and Raman spectroscopy. Both techniques detect slight structural defects in the SOI layer. If a pure crystalline silicon dielectric function is assumed for the SOI layer, the spectroscopic ellipsometry data fitting yields an unacceptably large discrepancy between the experimental and modeled data. The best fits for all the samples result in a dielectric function of the SOI layer that consists of a physical mixture of crystalline silicon and about 4 % to 7 % of amorphous silicon. Using such a mixture indicates that there are still some defects in the SOI layer when compared with the high-quality bulk crystalline silicon. This observation is further supported by Raman spectroscopy measurements. The Raman spectra of all SOI samples exhibit a feature at about 495 cm−1 that is not observed in the crystalline silicon spectrum. Features similar to the 495 cm−1 feature have been reported in the literature and attributed to dislocations or faults in the silicon lattice.

The present study examined the dysfunctional attitudes and the personality styles of 40 psychiatric outpatients with obsessive-compulsive disorder (OCD) and compared them to 33 outpatients with major depressive disorder (MDD) and 41 healthy controls (HC). Scores on Beck's Depression Inventory (BDI), Dysfunctional Attitude Scale (DAS), and Sociotropy-Autonomy Scale (SAS) were obtained for the three groups. Based on previous research it was predicted that higher levels of sociotropy subscales S 1 (concern about disapproval), and S 2 (attachment/separation concerns) would be specifically related to the diagnosis of OCD after controlling for differences in demographic variables and other psychiatric diagnoses. These hypotheses were confirmed. Significantly lower scores on subscale A 3 (solitary pursuits) was also found specifically related to OCD diagnoses. Higher scores on DAS and lower scores on autonomy subscale A 1 (independent achievement) were found to be particularly related to MDD. Implications of these findings for a cognitive model of the development of OCD are discussed.

Calmodulin (CaM), the ubiquitous, eukaryotic, bilobal calcium-binding regulatory protein, has been cleaved by thrombin to create two fragments, TM1 (1–106) and TM2 (107–148). NMR and CD results indicate that TM1 and TM2 can associate in the presence of Ca2+ to form a complex similar to native CaM, even though the cleavage site is not in the linker region between two helix-loop-helix domains, but rather within an α-helix. Cadmium-113 NMR results show that this complex has enhanced metal-ion binding properties when compared to either TM1 or TM2 alone. This complex can bind several CaM-binding target peptides, as shown by gel bandshift assays, circular dichroism spectra, and 13C NMR spectra of biosynthetically methyl-13C-Met-labeled TM1 and TM2; moreover, gel bandshift assays show that the addition of a target peptide strengthens the interactions between TM1 and TM2 and increases the stability of the complex. Cadmium-113 NMR spectra indicate that the TM1:TM2 complex can also bind the antipsychotic drug trifluoperazine. However, in contrast to CaM:peptide complexes, the TM1:TM2:peptide complexes are disrupted by 4 M urea; moreover, TM1 and TM2 in combination are unable to activate CaM-dependent enzymes. This suggests that TM1:TM2 mixtures cannot bind target molecules as tightly as intact CaM, or perhaps that binding occurs but additional interactions with the target enzymes that are necessary for proper activation are perturbed by the proteolytic cleavage. The results presented here reflect the importance of the existence of helix-loop-helix Ca2+-binding domains in pairs in proteins such as CaM, and extend the understanding of the association of such domains in this class of proteins in general.

Calmodulin (CaM) is a 148-residue regulatory calcium-binding protein that activates a wide range of target proteins and enzymes. Calcium-saturated CaM has a bilobal structure, and each domain has an exposed hydrophobic surface region where target proteins are bound. These two “active sites” of calmodulin are remarkably rich in Met residues. Here we have biosynthetically substituted (up to 90% incorporation) the unnatural amino acids ethionine (Eth) and norleucine (Nle) for the nine Met residues of CaM. The substituted proteins bind in a calcium-dependent manner to hydrophobic matrices and a synthetic peptide, encompassing the CaM-binding domain of myosin light-chain kinase (MLCK). Infrared and circular dichroism spectroscopy show that there are essentially no changes in the secondary structure of these proteins compared to wild-type CaM (WT-CaM). One- and two-dimensional NMR studies of the Eth-CaM and Nle-CaM proteins reveal that, while the core of the proteins is relatively unaffected by the substitutions, the two hydrophobic interaction surfaces adjust to accommodate the Eth and Nle residues. Enzyme activation studies with MLCK show that Eth-CaM and Nle-CaM activate the enzyme to 90% of its maximal activity, with little changes in dissociation constant. For calcineurin only 50% activation was obtained, and the KD for Nle-CaM also increased 3.5-fold compared with WT-CaM. These data show that the “active site” Met residues of CaM play a distinct role in the activation of different target enzymes, in agreement with site-directed mutagenesis studies of the Met residues of CaM.