A nitromethane solvate of 18-crown-6 was investigated by means of variable-temperature single-crystal X-ray diffraction in response to a report of abnormal unit cell contraction. Exceptionally large ...positive thermal expansion in two axial directions and negative thermal expansion along the third was confirmed. The underlying mechanism relies exclusively on weak electrostatic interactions to yield a linear thermal expansion coefficient of -129 × 10(-6) K(-1), the largest negative value yet observed for an organic inclusion compound.
An activation of pro-inflammatory cytokines in the central nervous system is associated with cognitive disturbances. This process is mediated by prostaglandins and cyclo-oxygenase-2 (COX-2). COX-2 ...inhibitors have been suggested to show beneficial effects in disorders associated with cognitive disturbance, although clinical effects on cognition have not been shown until today. Data from a schizophrenia study were reevaluated under the aspect whether an effect on the positive and negative syndrome scale (PANSS) factor cognition can be observed during therapy with the COX-2 inhibitor celecoxib add on to risperidone in comparison to riperidone alone. Beside the effect on the PANSS total score, the effect on the cognition factor was the most pronounced using the analysis of covariance compared to all other factors of the PANSS (p < 0.06). Although suggestions of basic research led to an expected therapeutic effect of COX-2 inhibitors on cognition, this effect could not yet be shown clinically. In schizophrenia, the effect on cognition contributes to the therapeutic effect of COX-2 inhibitors.
Recently completed NH3 volatilization field studies with urea suggest the urease inhibitor N‐(n‐butyl) thiophosphoric triamide (NBPT) has prolonged activity in alkaline relative to acidic soils. A ...laboratory incubation experiment was conducted at two temperatures (0.5 and 20°C) to determine whether NBPT degradation was affected by soil pH (alkaline vs. acidic) and to determine the impact on urea hydrolysis. Soil (10 g) from the surface horizon of a loam (pH 5.5) and a silt loam (pH 8.4) was placed in bottles and incubated up to 28 d in constant‐temperature chambers. A third soil was constructed by adding CaCO3 (0.3 g) to the loam soil (pH 8.2). Urea (20 mg) with and without NBPT (20 mg) was applied to each soil. High‐performance liquid chromatography–mass spectrometry analysis of KCl extracts revealed that NBPT degraded rapidly in the acidic soil compared with the alkaline soils (silt loam and loam with added CaCO3). Exponential decay constants for the acidic soil were 5.2 and 3.9 times larger than decay constants for the alkaline soils at 0.5 and 20°C, respectively. Urea hydrolysis rates were reduced by NBPT, and the response was greater for the alkaline soils (P < 0.0001). Hydrolysis was inhibited by 17.0 and 86.2% at 20°C and by 53.3 and 92.1% at 0.5°C for the acidic and alkaline soils, respectively. This study confirmed field observations that NBPT persistence and activity is greater in alkaline soils. Additional studies, including chemical hydrolysis and sorption, are needed to clarify the processes responsible for the rapid disappearance of NBPT from extracts of acidic soils.
It is demonstrated that guest replacement in a series of isoskeletal organic inclusion compounds can produce drastic changes in thermal expansion behavior. The compounds 1, 2, and 3 have 18-crown-6 ...as host molecule and nitromethane, acetonitrile, and iodomethane, respectively, as guests. Along the principal axis X1 the linear component of thermal expansion is negative for 1 and 2 but positive for 3. All three compounds have varying degrees of large volumetric thermal expansion, with coefficients of 378(22), 226(3), and 256(8) × 10–6 K–1 for 1, 2, and 3, respectively. Crystal structure analysis and computational methods were used to elucidate general features of the underlying mechanism of thermal expansion for the series. The contributions of several factors are described, including host–guest compatibility, electrostatic effects, and steric effects. A tilting mechanism gives rise to the negative components of thermal expansion in 1 and 2 but is inhibited by the large molecular volume of the guest in 3. In addition, the thermosalient effect was observed for 2. To our knowledge this is the first example of thermosalience reported for an inclusion compound.
We demonstrate exceptional twinning deformation in a molecular crystal upon application of mechanical stress. Crystal integrity is preserved and the deformation is associated with a large bending ...angle (65.44°). This is a new strategy to increase the magnitude of the dissipated energy in an organic solid comparable to that seen in alloys. By X-ray crystallographic analysis it was determined that a large molecular rearrangement at the twinning interface preserves the crystal integrity. Drastic molecular rearrangement at the twinning interface helps to preserve hydrogen bonding in the molecular rotation, which facilitates the large bending angle. The maximum shear strain of 218.81% and dissipated energy density of 1 MJ m
can significantly enhance mechanical damping of vibrations.
Although the Clinical Global Impression (CGI) and the Brief Psychiatric Rating Scale (BPRS) are both frequently used in drug trials for schizophrenia, their relative sensitivity in detecting ...differences between antipsychotics has not yet been examined. We therefore reanalyzed original patient data from all four pivotal, randomized controlled studies (n = 1205) that compared amisulpride with haloperidol in patients with schizophrenia. The sensitivity of the BPRS vs the CGI-improvement and the CGI-severity scales in detecting between-drug differences was estimated by calculating effect sizes and their 95% confidence intervals for both continuous (standardized mean differences) and dichotomous outcomes (odds ratios). The primary end points were the last observation carried forward results at study end points pooling all studies, but the results of the observed cases at different study weeks and the results of the single studies were also examined. The effect sizes derived from the BPRS and from the CGI were similar. When the single studies were pooled, all outcomes analyzed showed a statistically significant superiority of amisulpride compared to haloperidol as early as 2 weeks after initiation of treatment. The CGI may be as sensitive as the BPRS in detecting efficacy differences between antipsychotic drugs, although specific studies with truly independent ratings would be needed for confirmation. The fact that it takes only 1-2 min to fill in the CGI justifies its use in addition to more specific scales in drug trials for schizophrenia. Further development and evaluation of the CGI is warranted.
The Saccharomyces Genome Database (SGD) is a well-established, key resource for researchers studying Saccharomyces cerevisiae. In addition to updating and maintaining the official genomic sequence of ...this highly studied organism, SGD provides integrated data regarding gene functions and phenotypes, which are extracted from the published literature. The vast amount and variety of data housed in the database can prove challenging to navigate for the first-time user. Therefore, this chapter serves as an introduction describing how to search the database in order to discover new information. We introduce the different types of pages on the website, and describe how to manipulate the tables and diagrams therein to display, download, or analyze the data using various SGD tools.
OBJECTIVE: The "atypical" profile of the new antipsychotics clozapine, olanzapine, quetiapine, and risperidone has been linked to combined antagonism of serotonin 2 (5-HT2) and dopamine 2 (D2) ...receptors. Although amisulpride is a highly selective D3 D2 receptor antagonist, it is assumed to have atypical properties as well. The purpose of this article was to compare the atypical profile of amisulpride with that of the 5-HT2 D2 antagonists. METHOD: Randomized controlled trials that compared amisulpride with conventional antipsychotics or placebo for patients with schizophrenia were identified and included in a meta-analysis. The mean effect sizes found for amisulpride were compared with those of an updated meta-analysis of the 5-HT2 D2 antagonists. RESULTS: Eighteen randomized controlled trials of amisulpride (N=2,214) were found. In 11 studies of acutely ill patients it proved to be consistently more effective than conventional antipsychotics for global schizophrenic symptoms (measured with the Brief Psychiatric Rating Scale) and negative symptoms. Amisulpride is to date the only atypical antipsychotic for which several studies of patients suffering predominantly from negative symptoms have been published. In four such studies amisulpride was significantly more effective than placebo. Three small studies with conventional antipsychotics as comparators showed only a trend in favor of amisulpride in this regard. Amisulpride was associated with clearly lower use of antiparkinsonian medication and with fewer dropouts due to adverse events than conventional antipsychotics. CONCLUSIONS: These results cast some doubt on the notion that combined 5-HT2 D2 antagonism is the reason that the newer antipsychotic medications are effective for negative symptoms and have fewer extrapyramidal side effects.
With the intense and coherent x-ray pulses available from free-electron lasers, the possibility to transfer non-linear spectroscopic methods from the laser lab to the x-ray world arises. Advantages ...especially regarding selectivity and thus information content as well as an improvement of signal levels are expected. The use of coherences is especially fruitful and the example of coherent x-ray/optical sum-frequency generation is discussed. However, many non-linear x-ray methods still await discovery, partially due to the necessity for extremely adaptable and versatile instrumentation that can be brought to free-electron lasers for the analysis of the spectral content emitted from the sample into a continuous range of emission angles. Such an instrument (called MUSIX) is being developed and employed at FLASH, the free-electron laser in Hamburg and is described in this contribution together with first results.
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