The largest observed earthquakes occur on subduction interfaces and frequently cause widespread damage and loss of life. Understanding the rupture behavior of megathrust events is crucial for ...earthquake rupture physics, as well as for earthquake early-warning systems. However, the large variability in behavior between individual events seemingly defies a description with a simple unifying model. Here we use three source time function (STF) data sets for subduction zone earthquakes, with moment magnitude M
w ≥ 7, and show that such large ruptures share a typical universal behavior. The median STF is scalable between events with different sizes, grows linearly, and is nearly triangular. The deviations from the median behavior are multiplicative and Gaussian—that is, they are proportionally larger for larger events. Our observations suggest that earthquake magnitudes cannot be predicted from the characteristics of rupture onsets.
Anticancer metallodrugs based on ruthenium and osmium are among the most investigated and advanced non-platinum metallodrugs. Inorganic drug discovery with these agents has undergone considerable ...advances over the past two decades and has currently two representatives in active clinical trials. As many ruthenium and osmium metallodrugs are prodrugs, a key question to be addressed is how the molecular reactivity of such metal-based therapeutics dictates the selectivity and the type of interaction with molecular targets. Within this frame, this review introduces the field by the examples of the most advanced ruthenium lead structures. Then, global structure-activity relationships are discussed for ruthenium and osmium metallodrugs with respect to
in vitro
antiproliferative/cytotoxic activity and
in vivo
tumor-inhibiting properties, as well as pharmacokinetics. Determining and validating global mechanisms of action and molecular targets are still major current challenges. Moreover, significant efforts must be invested in screening
in vivo
tumor models that mimic human pathophysiology to increase the predictability for successful preclinical and clinical development of ruthenium and osmium metallodrugs.
The drug discovery process of ruthenium and osmium anticancer therapeutics is described, including global structure-activity relationships.
Anxiety disorders are common, complex psychiatric disorders with twin heritabilities of 30-60%. We conducted a genome-wide association study of Lifetime Anxiety Disorder (n
= 25 453, n
= 58 113) ...and an additional analysis of Current Anxiety Symptoms (n
= 19 012, n
= 58 113). The liability scale common variant heritability estimate for Lifetime Anxiety Disorder was 26%, and for Current Anxiety Symptoms was 31%. Five novel genome-wide significant loci were identified including an intergenic region on chromosome 9 that has previously been associated with neuroticism, and a locus overlapping the BDNF receptor gene, NTRK2. Anxiety showed significant positive genetic correlations with depression and insomnia as well as coronary artery disease, mirroring findings from epidemiological studies. We conclude that common genetic variation accounts for a substantive proportion of the genetic architecture underlying anxiety.
Synthesis protocols to convert
N
-formamides into isocyanides using three different dehydration reagents (
i.e. p
-toluenesulfonyl chloride (
p
-TsCl), phosphoryl trichloride (POCl
3
) and the ...combination of triphenylphosphane (PPh
3
) and iodine) were investigated and optimized, while considering the principles of green chemistry. Comparison of the yield and the E-factors of the different synthesis procedures revealed that, in contrast to the typically applied POCl
3
or phosgene derivatives,
p
-TsCl was the reagent of choice for non sterically demanding aliphatic mono- or di-
N
-formamides (yields up to 98% and lowest E-factor 6.45). Apart from a significantly reduced E-factor,
p
-TsCl is cheap, offers a simplified reaction protocol and work-up, and is less toxic compared to other dehydration reagents. Thus, this procedure offers easier and greener access to aliphatic isocyanide functionalities.
A more sustainable and easier applicable synthesis of aliphatic isocyanides in DMC is introduced using non-hazardous
p
-toluenesulfonyl chloride as dehydration reagent.
Childhood psychotic symptoms have been used as a subclinical phenotype of schizophrenia in etiological research and as a target for preventative interventions. However, recent studies have cast doubt ...on the specificity of these symptoms for schizophrenia, suggesting alternative outcomes such as anxiety and depression. Using a prospective longitudinal birth cohort we investigated whether childhood psychotic symptoms predicted a diagnosis of schizophrenia or other psychiatric disorders by 38 years of age.
Participants were drawn from a birth cohort of 1037 children from Dunedin, New Zealand, who were followed prospectively to 38 years of age (96% retention rate). Structured clinical interviews were administered at age 11 to assess psychotic symptoms and study members underwent psychiatric assessments at ages 18, 21, 26, 32 and 38 to obtain past-year DSM-III-R/IV diagnoses and self-reports of attempted suicides since adolescence.
Psychotic symptoms at age 11 predicted elevated rates of research diagnoses of schizophrenia and posttraumatic stress disorder (PTSD) and also suicide attempts by age 38, even when controlling for gender, social class and childhood psychopathology. No significant associations were found for persistent anxiety, persistent depression, mania or persistent substance dependence. Very few of the children presenting with age-11 psychotic symptoms were free from disorder by age 38.
Childhood psychotic symptoms were not specific to a diagnosis of schizophrenia in adulthood and thus future studies of early symptoms should be cautious in extrapolating findings only to this clinical disorder. However, these symptoms may be useful as a marker of adult mental health problems more broadly.
Isothiocyanates (ITCs) are typically prepared using amines and highly toxic reagents such as thiophosgene, its derivatives, or CS
2
. In this work, an investigation of a multicomponent reaction (MCR) ...using isocyanides, elemental sulfur and amines revealed that isocyanides can be converted to isothiocyanates using sulfur and catalytic amounts of amine bases, especially DBU (down to 2 mol%). This new catalytic reaction was optimized in terms of sustainability, especially considering benign solvents such as Cyrene™ or γ-butyrolactone (GBL) under moderate heating (40 °C). Purification by column chromatography was further optimized to generate less waste by maintaining high purity of the product. Thus,
E
-factors as low as 0.989 were achieved and the versatility of this straightforward procedure was shown by converting 20 different isocyanides under catalytic conditions, while obtaining moderate to high yields (34-95%).
Isothiocyanates were snythesized in a more sustainable manner by sulfurization of isocyanides with elemental sulfur using catalytic amounts of DBU (down to 2 mol%).
A rapid and effective dissolution and activation of cellulose was demonstrated by a reversible reaction of CO2 with the hydroxyl groups of the cellulose backbone in the presence of ...1,8-diazabicyclo5.4.0undec-7-ene (DBU). The dissolved cellulose was subsequently subjected to in situ derivatization with succinic anhydride without the need of any additional catalyst under very mild conditions. As a result of our optimization studies, cellulose was successfully converted to cellulose succinates with degrees of substitution (DS) ranging from 1.51 to 2.59, depending on the reaction conditions and the molar ratio of succinic anhydride. The optimized reaction conditions were successfully applied to different types of cellulose samples including microcrystalline cellulose (MCC) and organosolv wood pulp (WP), exhibiting similar conversions. Furthermore, the carboxylic acid moiety, introduced by the succinylation, was further converted via Passerini three-component reactions (Passerini-3CR) and Ugi four-component reactions (Ugi-4CR). 31P NMR revealed the quantitative conversion of carboxylic acid moieties on the cellulose backbone under mild conditions. All obtained products were thoroughly characterized by ATR-IR, 1H, 13C, and 31P NMR spectroscopies as well as by size exclusion chromatography (SEC). Thermal properties of the obtained products were investigated by differential scanning calorimetry (DSC) and by thermogravimetric analysis (TGA), revealing glass transitions (Tg) for all the Passerini and Ugi products between at 76–116 °C and high thermal stability between 263–290 °C. The reported methodology represents a very mild, highly efficient and sustainable route for the dissolution of cellulose and the synthesis of cellulose succinates. The subsequent modifications of the obtained cellulose succinates via multicomponent reactions resulted in materials with improved thermal properties and offers a straightforward and versatile modification strategy for cellulose.
Palladium nanoparticles stabilized by poly(vinylpyrrolidone) catalyze Tsuji-Trost allylations in water with very high turnover numbers. The di-allylation of methylene active compounds and the ...allylation of bio-based phenols was performed in high yield. The allylation of lignin showed a high selectivity towards the phenolic OH groups.
As surveillance of hospital-acquired pneumonia (HAP) is very resource intensive, alternatives for HAP surveillance are needed urgently. This study compared HAP rates according to routine discharge ...diagnostic codes of the International Classification of Diseases, 10th Revision (ICD-10; ICD-HAP) with HAP rates according to the validated surveillance definitions of the Hospitals in Europe Link for Infection Control through Surveillance (HELICS/IPSE; HELICS-HAP) by manual retrospective re-evaluation of patient records. The positive predictive value of ICD-HAP for HELICS-HAP was 0.35, and sensitivity was 0.59. Therefore, the currently available ICD-10-based routine discharge data do not allow reliable identification of patients with HAP.
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