The Relation of Shift Work Tolerance to the Circadian Adjustment

The amplitude and phasing of circadian rhythms are under discussion as possible predictors of tolerance to night work. In a field study, subjective sleepiness and oral temperature of 147 female nurses were measured at 2-hour intervals during a period with one morning shift and two consecutive night shifts. The nurses also filled out a questionnaire. Two types of tolerance indices were constructed: The “health index” was based on questions referring to general fatigue, gastrointestinal symptoms, and sleep disturbances, and the “sleepiness index” on the actual subjective ratings of sleepiness. According to the health index, the group with good tolerance had a larger circadian amplitude of the oral temperature rhythm on the day of the morning shift than the group with poor tolerance. However, with regard to the sleepiness index, the corresponding difference between the groups with good or poor tolerance was not significant. The data did not confirm the hypothesis that predicts a quick adjustment of the circadian rhythm when the circadian amplitude is small before the change to night work. The contradictory results found in this and in other studies do not yet permit prediction of tolerance to night work.     

Cohort study of multiple brain lesions in sport divers: role of a patent foramen ovale.

OBJECTIVE: To investigate the role of a patient foramen ovale in the pathogenesis of multiple brain lesions acquired by sport divers in the absence of reported decompression symptoms. DESIGN: Prospective double blind cohort study. SETTING: Diving clubs around Heidelberg and departments of neuroradiology and neurology. SUBJECTS: 87 sport divers with a minimum of 160 scuba dives (dives with self contained underwater breathing apparatus). MAIN OUTCOME MEASURES: Presence of multiple brain lesions visualised by cranial magnetic resonance imaging and presence and size of patent foramen ovale as documented by echocontrast transcranial Doppler ultrasonography. RESULTS: 25 subjects were found to have a right-to-left shunt, 13 with a patent foramen ovale of high haemodynamic relevance. A total of 41 brain lesions were detected in 11 divers. There were seven brain lesions in seven divers without a right-to-left shunt and 34 lesions in four divers with a right-to-left shunt. Multiple brain lesions occurred exclusively in three divers with a large patent foramen ovale (P = 0.004). CONCLUSIONS: Multiple brain lesions in sport divers were associated with presence of a large patent foramen ovale. This association suggests paradoxical gas embolism as the pathological mechanism. A patent foramen ovale of high haemodynamic relevance seems to be an important risk factor for developing multiple brain lesions in sport divers.     

Analysis of physical pore space characteristics of two pyrolytic biochars and potential as microhabitat

Plant and Soil - Biochar amendment to soil is a promising practice of enhancing productivity of agricultural systems. The positive effects on crop are often attributed to a promotion of beneficial...     

Synthesis and structure based optimization of novel Akt inhibitors

Based on a high throughput screening hit, pyrrolopyrimidine inhibitors of the Akt kinase are explored. X-ray co-crystal structures of two lead series results in the understanding of key binding interactions, the design of new lead series, and enhanced potency. The syntheses of these series and their biological activities are described. Spiroindoline 13j is found to have an Akt1 kinase IC(50) of 2.4+/-0.6 nM, Akt cell potency of 50+/-19 nM, and provides 68% inhibition of tumor growth in a mouse xenograft model (50 mg/kg, qd, po).     

Numb3 is an endocytosis adaptor for the inflammatory marker P-selectin

The endocytic protein Numb3 was found to bind to the cytosolic tail of the leukocyte adhesion receptor P-selectin. The N-terminal phosphotyrosine-binding (PTB) domain of Numb3 is responsible for this activity. An alanine scan revealed the FTNAAFD sequence as recognition region in P-selectin. Structural modeling of the interaction between the Numb PTB domain and the P-selectin tail suggests that both phenylalanines within the recognition sequence fit into hydrophobic cavities of the PTB surface. Their exchange for alanine gave Numb-negative mutants detaining the inhibition of P-selectin endocytosis by Numb PTB overexpression. Cells stable expressing P-selectins internalized the negative mutants markedly slower than the wild type. Consistent with other reports on the phosphorylation of Numb, we found that only the dephospho-Numb is able to bind P-selectin. Our observations demonstrate that Numb3 is an endocytic receptor for P-selectin and may be responsible for the rapid internalization of P-selectin when endothelial activation ends.     

The effect of an on the job training program -- stairclimbing -- on the physical working capacity of employees (author's transl)

Following medical screening and physical fitness testing (W170) 52 voltuntary employees in a 31-story administration building were formed into matched pairs and randomly allocated into intervention (stairclimbing) and control (lift) groups. The intervention group was asked to climb at least 25 floors/workday or 125 floors/week. the control group was asked to use only the lift. The intervention time was 10 weeks. The physiological measurements were made before and after the intervention. The number of stairs climbed was recorded daily in a diary. The heart rate was recorded continuously over one workday before and during the interventions. The average quantity of training in the final intervention group (n = 19) was 29.9 floors/workday or 36,790 kpm/week and in the control group 4.6 and 5980 correspondingly. The average training frequency was 4.3 in intervention and 1.4 climbs/workday in the control group. The average number of continuous floors used during climbing was 7.0 in intervention and 3.4 in control group. The average number of minutes on heart rate level of 130-159 beats/min during one workday was 7.8 in intervention and 1.6 in control group. The W170 (W/kg) increased 17.8% and the predicted VO2max (ml/min/kg) 15.1% in intervention group. The difference between the intervention group and the control group was significant (p less than 0.01). It was concluded, that stairclimbing is a suitable on the job physical activity program for middle-aged, untrained men.     

Discovery and synthesis of novel 4-aminopyrrolopyrimidine Tie-2 kinase inhibitors for the treatment of solid tumors

The synthesis and biological evaluation of novel Tie-2 kinase inhibitors are presented. Based on the pyrrolopyrimidine chemotype, several new series are described, including the benzimidazole series by linking a benzimidazole to the C5-position of the 4-amino-pyrrolopyrimidine core and the ketophenyl series synthesized by incorporating a ketophenyl group to the C5-position. Medicinal chemistry efforts led to potent Tie-2 inhibitors. Compound 15, a ketophenyl pyrrolopyrimidine urea analog with improved physicochemical properties, demonstrated favorable in vitro attributes as well as dose responsive and robust oral tumor growth inhibition in animal models.     

A 3D image filter for parameter-free segmentation of macromolecular structures from electron tomograms

3D image reconstruction of large cellular volumes by electron tomography (ET) at high (≤ 5 nm) resolution can now routinely resolve organellar and compartmental membrane structures, protein coats, cytoskeletal filaments, and macromolecules. However, current image analysis methods for identifying in situ macromolecular structures within the crowded 3D ultrastructural landscape of a cell remain labor-intensive, time-consuming, and prone to user-bias and/or error. This paper demonstrates the development and application of a parameter-free, 3D implementation of the bilateral edge-detection (BLE) algorithm for the rapid and accurate segmentation of cellular tomograms. The performance of the 3D BLE filter has been tested on a range of synthetic and real biological data sets and validated against current leading filters-the pseudo 3D recursive and Canny filters. The performance of the 3D BLE filter was found to be comparable to or better than that of both the 3D recursive and Canny filters while offering the significant advantage that it requires no parameter input or optimisation. Edge widths as little as 2 pixels are reproducibly detected with signal intensity and grey scale values as low as 0.72% above the mean of the background noise. The 3D BLE thus provides an efficient method for the automated segmentation of complex cellular structures across multiple scales for further downstream processing, such as cellular annotation and sub-tomogram averaging, and provides a valuable tool for the accurate and high-throughput identification and annotation of 3D structural complexity at the subcellular level, as well as for mapping the spatial and temporal rearrangement of macromolecular assemblies in situ within cellular tomograms.