Cation selectivity of the presequence translocase channel Tim23 is crucial for efficient protein import.

Virtually all mitochondrial matrix proteins and a considerable number of inner membrane proteins carry a positively charged, N-terminal presequence and are imported by the TIM23 complex (presequence translocase) located in the inner mitochondrial membrane. The voltage-regulated Tim23 channel constitutes the actual protein-import pore wide enough to allow the passage of polypeptides with a secondary structure. In this study, we identify amino acids important for the cation selectivity of Tim23. Structure based mutants show that selectivity is provided by highly conserved, pore-lining amino acids. Mutations of these amino acid residues lead to reduced selectivity properties, reduced protein import capacity and they render the Tim23 channel insensitive to substrates. We thus show that the cation selectivity of the Tim23 channel is a key feature for substrate recognition and efficient protein import

Particle Physics Explanations for Ultra High Energy Cosmic Ray Events

The origin of cosmic ray events with E \gsim 10^{11} GeV remains mysterious. In this talk I briefly summarize several proposed particle physics explanations: a breakdown of Lorentz invariance, the ``$Z-$burst'' scenario, new hadrons with masses of several GeV as primaries, and magnetic monopoles with mass below $10^{10}$ GeV as primaries. I then describe in a little more detail the idea that these events are due to the decays of very massive, long--lived exotic particles.Comment: Invited plenary talk at PASCOS03, Mumbai, India, January 2003; 13 pages, 1 figur

D-Matter

We study the properties and phenomenology of particle-like states originating from D-branes whose spatial dimensions are all compactified. They are non-perturbative states in string theory and we refer to them as D-matter. In contrast to other non-perturbative objects such as 't Hooft-Polyakov monopoles, D-matter states could have perturbative couplings among themselves and with ordinary matter. The lightest D-particle (LDP) could be stable because it is the lightest state carrying certain (integer or discrete) quantum numbers. Depending on the string scale, they could be cold dark matter candidates with properties similar to that of wimps or wimpzillas. The spectrum of excited states of D-matter exhibits an interesting pattern which could be distinguished from that of Kaluza-Klein modes, winding states, and string resonances. We speculate about possible signatures of D-matter from ultra-high energy cosmic rays and colliders.Comment: 25 pages, 5 figures, references adde

Electroweak jet cascading in the decay of superheavy particles

We study decays of superheavy particles $X$ into leptons. We show that they initiate cascades similar to QCD parton jets, if m_X\gsim 10^6 GeV. Electroweak cascading is studied and the energy spectra of the produced leptons are calculated in the framework of a broken SU(2) model of weak interactions. As application, important for the Z-burst model for ultrahigh energy cosmic rays, we consider decays of superheavy particles coupled on tree-level only to neutrinos and derive stringent limit for these decays from the observed diffuse extragalactic $\gamma$-ray flux.Comment: 4 pages, 1 eps figur

Risk assessment for the spread of Serratia marcescens within dental-unit waterline systems using Vermamoeba vermiformis

Vermamoeba vermiformis is associated with the biofilm ecology of dental-unit waterlines (DUWLs). This study investigated whether V. vermiformis is able to act as a vector for potentially pathogenic bacteria and so aid their dispersal within DUWL systems. Clinical dental water was initially examined for Legionella species by inoculating it onto Legionella selective-medium plates. The molecular identity/profile of the glassy colonies obtained indicated none of these isolates were Legionella species. During this work bacterial colonies were identified as a non-pigmented Serratia marcescens. As the water was from a clinical DUWL which had been treated with Alpron™ this prompted the question as to whether S. marcescens had developed resistance to the biocide. Exposure to Alpron™ indicated that this dental biocide was effective, under laboratory conditions, against S. marcescens at up to 1x108 colony forming units/millilitre (cfu/ml). V. vermiformis was cultured for eight weeks on cells of S. marcescens and Escherichia coli. Subsequent electron microscopy showed that V. vermiformis grew equally well on S. marcescens and E. coli (p = 0.0001). Failure to detect the presence of S. marcescens within the encysted amoebae suggests that V. vermiformis is unlikely to act as a vector supporting the growth of this newly isolated, nosocomial bacterium

Ataxia with oculomotor apraxia type 2: clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients

Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease due to mutations in the senataxin gene, causing progressive cerebellar ataxia with peripheral neuropathy, cerebellar atrophy, occasional oculomotor apraxia and elevated alpha-feto-protein (AFP) serum level. We compiled a series of 67 previously reported and 58 novel ataxic patients who underwent senataxin gene sequencing because of suspected AOA2. An AOA2 diagnosis was established for 90 patients, originating from 15 countries worldwide, and 25 new senataxin gene mutations were found. In patients with AOA2, median AFP serum level was 31.0 mu g/l at diagnosis, which was higher than the median AFP level of AOA2 negative patients: 13.8 mu g/l, P = 0.0004; itself higher than the normal level (3.4 mu g/l, range from 0.5 to 17.2 mu g/l) because elevated AFP was one of the possible selection criteria. Polyneuropathy was found in 97.5% of AOA2 patients, cerebellar atrophy in 96%, occasional oculomotor apraxia in 51%, pyramidal signs in 20.5%, head tremor in 14%, dystonia in 13.5%, strabismus in 12.3% and chorea in 9.5%. No patient was lacking both peripheral neuropathy and cerebellar atrophy. The age at onset and presence of occasional oculomotor apraxia were negatively correlated to the progression rate of the disease (P = 0.03 and P = 0.009, respectively), whereas strabismus was positively correlated to the progression rate (P = 0.03). An increased AFP level as well as cerebellar atrophy seem to be stable in the course of the disease and to occur mostly at or before the onset of the disease. One of the two patients with a normal AFP level at diagnosis had high AFP levels 4 years later, while the other had borderline levels. The probability of missing AOA2 diagnosis, in case of sequencing senataxin gene only in non-Friedreich ataxia non-ataxia-telangiectasia ataxic patients with AFP level >= 7 mu g/l, is 0.23% and the probability for a non-Friedreich ataxia non-ataxia-telangiectasia ataxic patient to be affected with AOA2 with AFP levels >= 7 mu g/l is 46%. Therefore, selection of patients with an AFP level above 7 mu g/l for senataxin gene sequencing is a good strategy for AOA2 diagnosis. Pyramidal signs and dystonia were more frequent and disease was less severe with missense mutations in the helicase domain of senataxin gene than with missense mutations out of helicase domain and deletion and nonsense mutations (P = 0.001, P = 0.008 and P = 0.01, respectively). The lack of pyramidal signs in most patients may be explained by masking due to severe motor neuropathy

Ultra-High Energy Neutrino Fluxes: New Constraints and Implications

We apply new upper limits on neutrino fluxes and the diffuse extragalactic component of the GeV gamma-ray flux to various scenarios for ultra high energy cosmic rays and neutrinos. As a result we find that extra-galactic top-down sources can not contribute significantly to the observed flux of highest energy cosmic rays. The Z-burst mechanism where ultra-high energy neutrinos produce cosmic rays via interactions with relic neutrinos is practically ruled out if cosmological limits on neutrino mass and clustering apply.Comment: 10 revtex pages, 9 postscript figure

Towards concolic testing for hybrid systems

Hybrid systems exhibit both continuous and discrete behavior. Analyzing hybrid systems is known to be hard. Inspired by the idea of concolic testing (of programs), we investigate whether we can combine random sampling and symbolic execution in order to effectively verify hybrid systems. We identify a sufficient condition under which such a combination is more effective than random sampling. Furthermore, we analyze different strategies of combining random sampling and symbolic execution and propose an algorithm which allows us to dynamically switch between them so as to reduce the overall cost. Our method has been implemented as a web-based checker named HYCHECKER. HYCHECKER has been evaluated with benchmark hybrid systems and a water treatment system in order to test its effectiveness.CPCI-S(ISTP)[email protected]; [email protected]

Ultra-High Energy Neutrino Fluxes and Their Constraints

Applying our recently developed propagation code we review extragalactic neutrino fluxes above 10^{14} eV in various scenarios and how they are constrained by current data. We specifically identify scenarios in which the cosmogenic neutrino flux, produced by pion production of ultra high energy cosmic rays outside their sources, is considerably higher than the "Waxman-Bahcall bound". This is easy to achieve for sources with hard injection spectra and luminosities that were higher in the past. Such fluxes would significantly increase the chances to detect ultra-high energy neutrinos with experiments currently under construction or in the proposal stage.Comment: 11 pages, 15 figures, version published in Phys.Rev.