On the inverse mean first passage matrix problem and the inverse M-matrix problem

The inverse mean first passage time problem is given a positive matrix M∈R^n,n, then when does there exist an n-state discrete-time homogeneous ergodic Markov chain C, whose mean first passage matrix is M? The inverse M-matrix problem is given a nonnegative matrix A, then when is A an inverse of an M-matrix. The main thrust of this paper is to show that the existence of a solution to one of the problems can be characterized by the existence of a solution to the other. In so doing we extend earlier results of Tetali and Fiedler.     

Transition Metal Ions: Charge Carriers that Mediate the Electron Capture Dissociation Pathways of Peptides

Electron capture dissociation (ECD) of model peptides adducted with first row divalent transition metal ions, including Mn²⁺, Fe²⁺, Co²⁺, Ni²⁺, Cu²⁺, and Zn²⁺, were investigated. Model peptides with general sequence of ZGGGXGGGZ were used as probes to unveil the ECD mechanism of metalated peptides, where X is either V or W; and Z is either R or N. Peptides metalated with different divalent transition metal ions were found to generate different ECD tandem mass spectra. ECD spectra of peptides metalated by Mn²⁺ and Zn²⁺ were similar to those generated by ECD of peptides adducted with alkaline earth metal ions. Series of c-/z-type fragment ions with and without metal ions were observed. ECD of Fe²⁺, Co²⁺, and Ni²⁺ adducted peptides yielded abundant metalated a-/y-type fragment ions; whereas ECD of Cu²⁺ adducted peptides generated predominantly metalated b-/y-type fragment ions. From the present experimental results, it was postulated that electronic configuration of metal ions is an important factor in determining the ECD behavior of the metalated peptides. Due presumably to the stability of the electronic configuration, metal ions with fully-filled (i.e., Zn²⁺) and half filled (i.e., Mn²⁺) d-orbitals might not capture the incoming electron. Dissociation of the metal ions adducted peptides would proceed through the usual ECD channel(s) via “hot-hydrogen” or “superbase” intermediates, to form series of c-/z ^•- fragments. For other transition metal ions studied, reduction of the metal ions might occur preferentially. The energy liberated by the metal ion reduction would provide enough internal energy to generate the “slow-heating” type of fragment ions, i.e., metalated a-/y- fragments and metalated b-/y- fragments.     

Formation of Peptide Radical Cations (M<Superscript>+·</Superscript>) in Electron Capture Dissociation of Peptides Adducted with Group IIB Metal Ions

Peptides adducted with different divalent Group IIB metal ions (Zn²⁺, Cd²⁺, and Hg²⁺) were found to give very different ECD mass spectra. ECD of Zn²⁺ adducted peptides gave series of c-/z-type fragment ions with and without metal ions. ECD of Cd²⁺ and Hg²⁺ adducted model peptides gave mostly a-type fragment ions with M^+• and fragment ions corresponding to losses of neutral side chain from M^+•. No detectable a-ions could be observed in ECD spectra of Zn²⁺ adducted peptides. We rationalized the present findings by invoking both proton-electron recombination and metal-ion reduction processes. As previously postulated, divalent metal-ions adducted peptides could adopt several forms, including (a) [M + Cat]²⁺, (b) [(M + Cat – H) + H]²⁺, and (c) [(M + Cat – 2H) + 2H]²⁺. The relative population of these precursor ions depends largely on the acidity of the metal–ion peptide complexes. Peptides adducted with divalent metal-ions of small ionic radii (i.e., Zn²⁺) would form predominantly species (b) and (c); whereas peptides adducted with metal ions of larger ionic radii (i.e., Hg²⁺) would adopt predominantly species (a). Species (b) and (c) are believed to be essential for proton-electron recombination process to give c-/z-type fragments via the labile ketylamino radical intermediates. Species (c) is particularly important for the formation of non-metalated c-/z-type fragments. Without any mobile protons, species (a) are believed to undergo metal ion reduction and subsequently induce spontaneous electron transfer from the peptide moiety to the charge-reduced metal ions. Depending on the exothermicity of the electron transfer reaction, the peptide radical cations might be formed with substantial internal energy and might undergo further dissociation to give structural related fragment ions.     

Proteome profiling reveals potential cellular targets of staurosporine using a clickable cell-permeable probe

A clickable, affinity-based probe (AfBP), which was modified from staurosporine (a natural product kinase inhibitor), has been synthesized and used in situ for activity-based proteome profiling of potential cellular targets of staurosporine in HepG2 cancer cells.     

Highly sensitive fluorescence detection system for microfluidic lab-on-a-chip

We demonstrate a compact, low cost and practical fluorescence detection system for lab-on-a-chip applications. The system comprises a commercially available InGaN light emitting diode (501 nm) as light source, an organic or silicon photodiode detector, absorptive dye coated colour filters and linear and reflective polarisers. An injection moulded polystyrene microfluidic chip is used as the platform for fluorescence immunoassays for cardiac markers myoglobin and CK-MB. The optical limit of detection (LOD) is measured using a TransFluoSphere? suspension at 5.6 × 10(4) beads μl(-1) which can be equated to ～3 nM fluorescein equivalent concentration. The LOD for the human plasma immunoassays is measured as 1.5 ng ml(-1) for both myoglobin and CK-MB.     

Applications of cavity ring-down spectroscopy to high precision isotope ratio measurement of 13C/12C in carbon dioxide

Recent measurements of carbon isotopes in carbon dioxide using near-infrared, diode-laser-based cavity ring-down spectroscopy (CRDS) are presented. The CRDS system achieved good precision, often better than 0.2 per thousand, for 4% CO2 concentrations, and also achieved 0.15-0.25 per thousand precision in a 78 min measurement time with cryotrap-based pre-concentration of ambient CO2 concentrations (360 ppmv). These results were obtained with a CRDS system possessing a data rate of 40 ring-downs per second and a loss measurement of 4.0 x 10(-11) cm(-1) Hz(-1/2). Subsequently, the measurement time has been reduced to under 10 min. This standard of performance would enable a variety of high concentration (3-10%) isotopic measurements, such as medical human breath analysis or animal breath experiments. The extension of this ring-down to the 2 microm region would enable isotopic analysis at ambient concentrations, which, combined with the small size, robust design, and potential for frequent measurements at a remote site, make CRDS technology attractive for remote atmospheric measurement applications.