CiteULike: Author Holtkamp

Anticonvulsant properties of hypothermia in experimental status epilepticus.

FC Schmitt — 2008-07-18T16:15:50-00:00

Neurobiology of disease, Vol. 23, No. 3. (September 2006), pp. 689-696.

Status epilepticus in patients often does not respond to first-line anticonvulsants, and subsequent treatment escalation with continuous intravenous anesthetics may be associated with significant side-effects. Therefore, alternative treatment regimens are urgently needed. Hypothermia has been shown to reduce excitatory transmission and may thus serve as an interesting adjunct in the management of status epilepticus. In the current experiments, three treatment groups were compared. Animals with self-sustaining status epilepticus were treated with external cooling for 3 h, with low-dose diazepam, or with a combination of both. The effect of these regimens on epileptic activity was compared with untreated controls. Animals that underwent cooling were rewarmed, and all animals were monitored for 5 h to assess occurrence and severity of motor seizures and frequency and amplitude of spontaneous epileptic discharges. Cooling alone significantly reduced number and severity of motor seizures but did not alter epileptic discharges. Cooling in addition to low-dose diazepam significantly diminished amplitudes and frequencies of epileptic discharges, while diazepam alone had only a minor reducing effect on discharge amplitudes. However, at later stages of status epilepticus, diazepam significantly reduced motor seizures. Following rewarming, the discharge frequency tended to increase again, suggesting partial reversibility. The current experiments show that in status epilepticus hypothermia exhibits anticonvulsant effects which are most pronounced if co-administered with low-dose diazepam. The results still require confirmation in other animal models and also clinical studies are urgently needed. However, our data indicate that cooling could well become a future adjunct in the treatment of status epilepticus in patients.

Information Resources in High-Energy Physics: Surveying the Present Landscape and Charting the Future Course

Anne Gentil-Beccot — 2008-04-18T21:48:45-00:00

(16 Apr 2008)

Access to previous results is of paramount importance in the scientific process. Recent progress in information management focuses on building e-infrastructures for the optimization of the research workflow, through both policy-driven and user-pulled dynamics. For decades, High-Energy Physics (HEP) has pioneered innovative solutions in the field of information management and dissemination. In light of a transforming information environment, it is important to assess the current usage of information resources by researchers and HEP provides a unique test-bed for this assessment. A survey of about 10% of practitioners in the field reveals usage trends and information needs. Community-based services, such as the pioneering arXiv and SPIRES systems, largely answer the need of the scientists, with a limited but increasing fraction of younger users relying on Google. Commercial services offered by publishers or database vendors are essentially unused in the field. The survey offers an insight into the most important features that users require to optimize their research workflow. These results inform the future evolution of information management in HEP and, as these researchers are traditionally “early adopters” of innovation in scholarly communication, can inspire developments of disciplinary repositories serving other communities.

On formal quantum group laws

Ralf Holtkamp — 2008-05-05T23:05:08-00:00

Archiv der Mathematik, Vol. 73, No. 2. (1999), pp. 90-103.

There exist natural generalizations of the concept of formal groups laws for noncommutative power series. This is a note on formal quantum group laws and quantum group law chunks. Formal quantum group laws correspond to noncommutative (topological) Hopf algebra structures on free associative power series algebras $k\langle\! \langle x_1,s,x_m \rangle\! \rangle $, k a field. Some formal quantum group laws occur as completions of noncommutative Hopf algebras (quantum groups). By truncating formal power series, one gets quantum group law chunks. ¶If the characteristic of k is 0, the category of (classical) formal group laws of given dimension m is equivalent to the category of m-dimensional Lie algebras. Given a formal group law or quantum group law (chunk), the corresponding Lie structure constants are determined by the coefficients of its chunk of degree 2. Among other results, a classification of all quantum group law chunks of degree 3 is given. There are many more classes of strictly isomorphic chunks of degree 3 than in the classical case.

Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells.

S Holtkamp — 2008-03-12T09:37:34-00:00

Blood, Vol. 108, No. 13. (15 December 2006), pp. 4009-4017.

Adoptive transfer of dendritic cells (DCs) transfected with in vitro-transcribed, RNA-encoding, tumor-associated antigens has recently entered clinical testing as a promising approach for cancer immunotherapy. However, pharmacokinetic exploration of RNA as a potential drug compound and a key aspect of clinical development is still pending. While investigating the impact of different structural modifications of RNA molecules on the kinetics of the encoded protein in DCs, we identified components located 3' of the coding region that contributed to a higher transcript stability and translational efficiency. With the use of quantitative reverse transcription-polymerase chain reaction (RT-PCR) and eGFP variants to measure transcript amounts and protein yield, we showed that a poly(A) tail measuring 120 nucleotides compared with a shorter one, an unmasked poly(A) tail with a free 3' end rather than one extended with unrelated nucleotides, and 2 sequential beta-globin 3' untranslated regions cloned head to tail between the coding region and the poly(A) tail each independently enhanced RNA stability and translational efficiency. Consecutively, the density of antigen-specific peptide/MHC complexes on the transfected cells and their potency to stimulate and expand antigen-specific CD4+ and CD8+ T cells were also increased. In summary, our data provide a strategy for optimizing RNA-transfected DC vaccines and a basis for defining release criteria for such vaccine preparations.