Low Cohomogeneity and Polar Actions on Exceptional Compact Lie Groups

We study isometric Lie group actions on the compact exceptional groups E6, E7, E8, F4 and G2 endowed with a biinvariant metric. We classify polar actions on these groups. We determine all isometric actions of cohomogeneity less than three on E6, E7, F4 and all isometric actions of cohomogeneity less than 20 on E8. Moreover we determine the principal isotropy algebras for all isometric actions on G2.Comment: 27 pages; introduction rewritten; references updated; final version; to appear in Transformation Group

Phase I dose-escalation and pharmacokinetic study of temozolomide (SCH 52365) for refractory or relapsing malignancies

Temozolomide, an oral cytotoxic agent with approximately 100% bioavailability after one administration, has demonstrated schedule-dependent clinical activity against highly resistant cancers. Thirty patients with minimal prior chemotherapy were enrolled in this phase I trial to characterize the drug's safety, pharmacokinetics and anti-tumour activity, as well as to assess how food affects oral bioavailability. To determine dose-limiting toxicities (DLT) and the maximum tolerated dose (MTD), temozolomide 100–250 mg m−2 was administered once daily for 5 days every 28 days. The DLT was thrombocytopenia, and the MTD was 200 mg m−2 day−1. Subsequently, patients received the MTD to study how food affects the oral bioavailability of temozolomide. When given orally once daily for 5 days, temozolomide was well tolerated and produced a non-cumulative, transient myelosuppression. The most common non-haematological toxicities were mild to moderate nausea and vomiting. Clinical activity was observed against several advanced cancers, including malignant glioma and metastatic melanoma. Temozolomide demonstrated linear and reproducible pharmacokinetics and was rapidly absorbed (mean Tmax ~1 h) and eliminated (mean t1/2 = 1.8 h). Food produced a slight reduction (9%) in absorption of temozolomide. Temozolomide 200 mg m−2 day−1 for 5 days, every 28 days, is recommended for phase II studies. © 1999 Cancer Research Campaig

Tight junctions and the modulation of barrier function in disease

Tight junctions create a paracellular barrier in epithelial and endothelial cells protecting them from the external environment. Two different classes of integral membrane proteins constitute the tight junction strands in epithelial cells and endothelial cells, occludin and members of the claudin protein family. In addition, cytoplasmic scaffolding molecules associated with these junctions regulate diverse physiological processes like proliferation, cell polarity and regulated diffusion. In many diseases, disruption of this regulated barrier occurs. This review will briefly describe the molecular composition of the tight junctions and then present evidence of the link between tight junction dysfunction and disease

Frequency-dependent effects of oscillatory-tDCS on EEG oscillations. A study with better oscillation detection method (BOSC)

Oscillating transcranial direct current stimulation (osc-tDCS) modulates the spontaneous brain activity in a frequency-specific manner. Most studies evaluated cortical effects of osc-tDCS through spectral analysis measures, without differentiating components associated with rhythmic and non-rhythmic activity. Since osc-tDCS mainly affects brain oscillatory activity, our aim was to investigate on the specific changes of EEG oscillations following a frontal osc-tDCS at 0.8 and at 5 Hz. 20 healthy subjects (26.8 ± 2.5 years) participated in one of two experiments (Exp.1= 0.8-Hz tDCS, n= 10; Exp.2= 5-Hz tDCS, n= 10), consisting of 3 within-subject sessions: two active conditions with different stimulation polarity (anodal osctDCS, cathodal osc-tDCS), and a control condition (sham). EEG oscillatory components (28 cortical derivations) at the stimulation frequency were measured by the Better OSCillation detection method (BOSC). Variations between before and after the osc-tDCS were compared between conditions as a function of polarity (anodal vs. cathodal vs. sham) and frequency (0.8 vs. 5 Hz) of stimulation. The main finding is a significant local increase of 0.81-Hz slow oscillations (F1,18=19.97; p=0.0004) and 5.3-Hz theta oscillations (F1,18=26.93; p= 0.0001) after 5 Hz compared to 0.8-Hz tDCS. Our study shows larger frequency-specific and cross-frequency effects of 5-Hz compared to 0.8-Hz stimulation, not revealed by conventional FFT analyses. This finding is consistent with a more effective induction of EEG synchronization during wakefulness by means of a stimulation in the theta range, and it suggests to combine measurement of EEG power and EEG oscillations in future studies involving transcranial stimulations