Prototype Detector for Ultrahigh Energy Neutrino Detection

Necessary technical experience is being gained from successful construction and deployment of current prototype detectors to search for UHE neutrinos in Antarctica, Lake Baikal in Russia, and the Mediterranean. The prototype detectors have also the important central purpose of determining whether or not UHE neutrinos do in fact exist in nature by observation of at least a few UHE neutrino-induced leptons with properties that are not consistent with expected backgrounds. We discuss here the criteria for a prototype detector to accomplish that purpose in a convincing way even if the UHE neutrino flux is substantially lower than predicted at present.Comment: 18 pages, 8 figures, submitted to Astroparticle Physic

Do All Integrable Evolution Equations Have the Painlev\'e Property?

We examine whether the Painleve property is necessary for the integrability of partial differential equations (PDEs). We show that in analogy to what happens in the case of ordinary differential equations (ODEs) there exists a class of PDEs, integrable through linearisation, which do not possess the Painleve property. The same question is addressed in a discrete setting where we show that there exist linearisable lattice equations which do not possess the singularity confinement property (again in analogy to the one-dimensional case).Comment: Published in SIGMA (Symmetry, Integrability and Geometry: Methods and Applications) at http://www.emis.de/journals/SIGMA

Desensitization is a property of the cholinergic binding region of the nicotinic acetylcholine receptor, not of the receptor-integral ion channel

The reversible acctylchollne esternse inhibitor (-}.physostiilmine (¢serine) is th© prolotypc of a new class of nie~tinlc ucetylcholinc receptor (nAChR) activating liga,ds: it induces cation fluxes into nAChR.rich membrane vesicl~s from 7~r#eda marmoeata cle~:tric tissue even under condl. lions of antalionist blocked :tcctylcholin~ binding sil~s (Okonjo, Kuhlm~mn. Maelicke. Neuron, in press). This su~tlest's that escrine exerts it~ than. nel.activating proi'~rty via binding sites at the nAChR separate from those of tile natural transmitter. We now report thllt eserine e'-m activate the channel wen when the receptor has t~en preincub~ttcd (des©nsitiz©d) with elevated concentrations of acetylcholi~e, Titus the confornudional state Of the receptor corresponding to de~nsitixation is confined to the transmitter bindinB rclli0n, leaving the ch=tr'4nel fully activatable ,- albeit only from other than the tr~msmitter bindin~ site(s)

A second pathway of activation of the Torpedo acetylcholine receptor channel

We have studied the interaction of the reversible acetylcholine esterase inhibitor (-)physostigmine (D-eserine) with the nicotinic acetylcholine receptor (nAChR) from Torpedo marmorata electric tissue by means of ligandinduced ion flux into nAChR-rich membrane vesicles and of equilibrium binding. We find that (—)physostigmine induces cation flux (and also binds to the receptor) even in the presence of saturating concentrations of antagonists of acetylcholine, such as D-tubocurarine, a-bungarotoxin or antibody WF6, The direct action on the acetylcholine receptor is not affected by removal of the methylcarbamate function from the drug and thus is not due to carbamylation of the receptor. Antibodies FKl and benzoquinonium antagonize channel activation (and binding) of eserine, suggesting that the eserine binding site(s) is separate from, but adjacent to, the acetylcholine binding site at the receptor. In addition to the channel activating site(s) with an affinity of binding in the 50 nM range, there exists a further class of low-affinity (K^ ~ mM) sites from which eserine acts as a direct blocker of the acetylcholine-activatcd channel. Our results suggest the existence of a second pathway of activation of the nAChR channel

The challenging problem of disease staging in human African trypanosomiasis (sleeping sickness): a new approach to a circular question

Human African trypanosomiasis (HAT), also known as sleeping sickness, puts millions of people at risk in sub-Saharan Africa and is a neglected parasitic disease that is almost always fatal if untreated or inadequately treated. HAT manifests itself in two stages that are difficult to distinguish clinically. The problem of staging in HAT is extremely important since treatment options, some of which are highly toxic, are directly linked to the disease stage. Several suggested investigations for disease staging have been problematic because of the lack of an existing gold standard with which to compare new clinical staging markers. The somewhat arbitrary current criteria based on the cerebrospinal fluid (CSF) white blood cell (WBC) count have been widely used, but the new potential biomarkers are generally compared with these, thereby making the problem somewhat circular in nature. We propose an alternative ‘reverse’ approach to address this problem, conceptualised as using appropriate statistical methods to test the performance of combinations of established laboratory variables as staging biomarkers to correlate with the CSF WBC/trypanosomes and clinical features of HAT. This approach could lead to the use of established laboratory staging markers, potentially leading to a gold standard for staging and clinical follow-up of HAT