Web-oriented Event Processing

How can the Web be made situation-aware? Event processing is a suitable technology for gaining the necessary real-time results. The Web, however, has many users and many application domains. Thus, we developed multi-schema friendly data models allowing the re-use and mix from diverse users and application domains. Furthermore, our methods describe protocols to exchange events on the Web, algorithms to execute the language and to calculate access rights

Quantal charge redistributions accompanying the structural transitions of sodium channels.

Asymmetric displacement currents, Ig, associated with the gating of nerve sodium channels have been recorded in cell-attached macropatches of Xenopus laevis oocytes injected with exogenous mRNA coding for rat-brain-II sodium channels. The Ig properties were found to be similar to those of gating currents previously observed in native nerve preparations. Ig fluctuations were measured in order to ascertain the discreteness of the conformational changes which precede the channel opening. The autocorrelation of the fluctuations is consistent with a shot-like character of the elementary Ig contributions. The variance of the fluctuations indicates that most of the gating-charge movement that accompanies the activation of a single sodium channel occurs in 2 to 3 brief packets, each carrying an equivalent of about 2.3 electron charges

A single point mutation confers tetrodotoxin and saxitoxin insensitivity on the sodium channel II.

A single point mutation of the rat sodium channel II reduces its sensitivity to tetrodotoxin and saxitoxin by more than three orders of magnitude. The mutation replaces glutamic acid 387 with a glutamine and has only slight effects on the macroscopic current properties, as measured under voltage-clamp in Xenopus oocytes injected with the corresponding cDNA-derived mRNA

Die Giftwirkung arteigener Eiweißstoffe 1 )

n/

Support immersion endoscopy in post-extraction alveolar bone chambers: a new window for microscopic bone imaging in Vivo

Using an endoscopic approach, small intraoral bone chambers, which are routinely obtained during tooth extraction and implantation, provide visual in vivo access to internal bone structures. The aim of the present paper is to present a new method to quantify bone microstructure and vascularisation in vivo. Ten extraction sockets and 6 implant sites in 14 patients (6 men / 8 women) were examined by support immersion endoscopy (SIE). After tooth extraction or implant site preparation, microscopic bone analysis (MBA) was performed using short distance SIE video sequences of representative bone areas for off-line analysis with ImageJ. Quantitative assessment of the microstructure and vascularisation of the bone in dental extraction and implant sites in vivo was performed using ImageJ. MBA revealed bone morphology details such as unmineralised and mineralised areas, vascular canals and the presence of bleeding through vascular canals. Morphometric examination revealed that there was more unmineralised bone and less vascular canal area in the implant sites than in the extraction sockets

Web-oriented Event Processing

How can the Web be made situation-aware? Event processing is a suitable technology for gaining the necessary real-time results. The Web, however, has many users and many application domains. Thus, we developed multi-schema friendly data models allowing the re-use and mix from diverse users and application domains. Furthermore, our methods describe protocols to exchange events on the Web, algorithms to execute the language and to calculate access rights

Cell Cycle–related Changes in the Conducting Properties of r-eag K+ Channels

Release from arrest in G2 phase of the cell cycle causes profound changes in rat ether-à-go-go (r-eag) K+ channels heterologously expressed in Xenopus oocytes. The most evident consequence of the onset of maturation is the appearance of rectification in the r-eag current. The trigger for these changes is located downstream of the activation of mitosis-promoting factor (MPF). We demonstrate here that the rectification is due to a voltage-dependent block by intracellular Na+ ions. Manipulation of the intracellular Na+ concentration indicates that the site of Na+ block is located ∼45% into the electrical distance of the pore and is only present in oocytes undergoing maturation. Since the currents through excised patches from immature oocytes exhibited a fast rundown, we studied CHO-K1 cells permanently transfected with r-eag. These cells displayed currents with a variable degree of block by Na+ and variable permeability to Cs+. Partial synchronization of the cultures in G0/G1 or M phases of the cell cycle greatly reduced the variability. The combined data obtained from mammalian cells and oocytes strongly suggest that the permeability properties of r-eag K+ channels are modulated during cell cycle–related processes

Tumor cell-selective apoptosis induction through targeting of KV10.1 via bifunctional TRAIL antibody

<p>Abstract</p> <p>Background</p> <p>The search for strategies to target ion channels for therapeutic applications has become of increasing interest. Especially, the potassium channel K_V10.1 (Ether-á-go-go) is attractive as target since this surface protein is virtually not detected in normal tissue outside the central nervous system, but is expressed in approximately 70% of tumors from different origins.</p> <p>Methods</p> <p>We designed a single-chain antibody against an extracellular region of K_V10.1 (scFv62) and fused it to the human soluble TRAIL. The K_V10.1-specific scFv62 antibody -TRAIL fusion protein was expressed in CHO-K1 cells, purified by chromatography and tested for biological activity.</p> <p>Results</p> <p>Prostate cancer cells, either positive or negative for K_V10.1 were treated with the purified construct. After sensitization with cytotoxic drugs, scFv62-TRAIL induced apoptosis only in K_V10.1-positive cancer cells, but not in non-tumor cells, nor in tumor cells lacking K_V10.1 expression. In co-cultures with K_V10.1-positive cancer cells the fusion protein also induced apoptosis in bystander K_V10.1-negative cancer cells, while normal prostate epithelial cells were not affected when present as bystander.</p> <p>Conclusions</p> <p>K_V10.1 represents a novel therapeutic target for cancer. We could design a strategy that selectively kills tumor cells based on a K_V10.1-specific antibody.</p

The potassium channel Ether à go-go is a novel prognostic factor with functional relevance in acute myeloid leukemia

<p>Abstract</p> <p>Background</p> <p>The voltage-gated potassium channel hEag1 (K_V10.1) has been related to cancer biology. The physiological expression of the human channel is restricted to the brain but it is frequently and abundantly expressed in many solid tumors, thereby making it a promising target for a specific diagnosis and therapy. Because chronic lymphatic leukemia has been described not to express hEag1, it has been assumed that the channel is not expressed in hematopoietic neoplasms in general.</p> <p>Results</p> <p>Here we show that this assumption is not correct, because the channel is up-regulated in myelodysplastic syndromes, chronic myeloid leukemia and almost half of the tested acute myeloid leukemias in a subtype-dependent fashion. Most interestingly, channel expression strongly correlated with increasing age, higher relapse rates and a significantly shorter overall survival. Multivariate Cox regression analysis revealed hEag1 expression levels in AML as an independent predictive factor for reduced disease-free and overall survival; such an association had not been reported before. As a functional correlate, specific hEag1 blockade inhibited the proliferation and migration of several AML cell lines and primary cultured AML cells <it>in vitro</it>.</p> <p>Conclusion</p> <p>Our observations implicate hEag1 as novel target for diagnostic, prognostic and/or therapeutic approaches in AML.</p