Site-selective protein modification via disulfide rebridging for fast tetrazine/trans-cyclooctene bioconjugation

An inverse electron demand Diels–Alder reaction between tetrazine and trans-cyclooctene (TCO) holds great promise for protein modification and manipulation. Herein, we report the design and synthesis of a tetrazine-based disulfide rebridging reagent, which allows the site-selective installation of a tetrazine group into disulfide-containing peptides and proteins such as the hormone somatostatin (SST) and the antigen binding fragment (Fab) of human immunoglobulin G (IgG). The fast and efficient conjugation of the tetrazine modified proteins with three different TCO-containing substrates to form a set of bioconjugates in a site-selective manner was successfully demonstrated for the first time. Homogeneous, well-defined bioconjugates were obtained underlining the great potential of our method for fast bioconjugation in emerging protein therapeutics. The formed bioconjugates were stable against glutathione and in serum, and they maintained their secondary structure. With this work, we broaden the scope of tetrazine chemistry for site-selective protein modification to prepare well-defined SST and Fab conjugates with preserved structures and good stability under biologically relevant conditions

Manipulating the magnetic state of a carbon nanotube Josephson junction using the superconducting phase

The magnetic state of a quantum dot attached to superconducting leads is experimentally shown to be controlled by the superconducting phase difference across the dot. This is done by probing the relation between the Josephson current and the superconducting phase difference of a carbon nanotube junction whose Kondo energy and superconducting gap are of comparable size. It exhibits distinctively anharmonic behavior, revealing a phase mediated singlet to doublet transition. We obtain an excellent quantitative agreement with numerically exact quantum Monte Carlo calculations. This provides strong support that we indeed observed the finite temperature signatures of the phase controlled zero temperature level-crossing transition originating from strong local electronic correlations.Comment: 5 pages, 4 figures + supp. material

Angular Momentum Profiles of Warm Dark Matter Halos

We compare the specific angular momentum profiles of virialized dark halos in cold dark matter (CDM) and warm dark matter (WDM) models using high-resolution dissipationless simulations. The simulations were initialized using the same set of modes, except on small scales, where the power was suppressed in WDM below the filtering length. Remarkably, WDM as well as CDM halos are well-described by the two-parameter angular momentum profile of Bullock et al. (2001), even though the halo masses are below the filtering scale of the WDM. Although the best-fit shape parameters change quantitatively for individual halos in the two simulations, we find no systematic variation in profile shapes as a function of the dark matter type. The scatter in shape parameters is significantly smaller for the WDM halos, suggesting that substructure and/or merging history plays a role producing scatter about the mean angular momentum distribution, but that the average angular momentum profiles of halos originate from larger-scale phenomena or a mechanism associated with the virialization process. The known mismatch between the angular momentum distributions of dark halos and disk galaxies is therefore present in WDM as well as CDM models. Our WDM halos tend to have a less coherent (more misaligned) angular momentum structure and smaller spin parameters than do their CDM counterparts, although we caution that this result is based on a small number of halos.Comment: 5 pages, 1 figure, Submitted to ApJ

Mg II Absorption Systems in SDSS QSO Spectra

We present the results of a MgII absorption-line survey using QSO spectra from the SDSS EDR. Over 1,300 doublets with rest equivalent widths greater than 0.3\AA and redshifts $0.366 \le z \le 2.269$ were identified and measured. We find that the $\lambda2796$ rest equivalent width ($W_0^{\lambda2796}$) distribution is described very well by an exponential function $\partial N/\partial W_0^{\lambda2796} = \frac{N^*}{W^*} e^{-\frac{W_0}{W^*}}$, with $N^*=1.187\pm0.052$ and $W^*=0.702\pm0.017$\AA. Previously reported power law fits drastically over-predict the number of strong lines. Extrapolating our exponential fit under-predicts the number of $W_0 \le 0.3$\AA systems, indicating a transition in $dN/dW_0$ near $W_0 \simeq 0.3$\AA. A combination of two exponentials reproduces the observed distribution well, suggesting that MgII absorbers are the superposition of at least two physically distinct populations of absorbing clouds. We also derive a new redshift parameterization for the number density of $W_0^{\lambda2796} \ge 0.3$\AA lines: $N^*=1.001\pm0.132(1+z)^{0.226\pm0.170}$ and $W^*=0.443\pm0.032(1+z)^{0.634\pm 0.097}$\AA. We find that the distribution steepens with decreasing redshift, with $W^*$ decreasing from $0.80\pm0.04$\AA at $z=1.6$ to $0.59\pm0.02$\AA at $z=0.7$. The incidence of moderately strong MgII $\lambda2796$ lines does not show evidence for evolution with redshift. However, lines stronger than $\approx 2$\AA show a decrease relative to the no-evolution prediction with decreasing redshift for $z \lesssim 1$. The evolution is stronger for increasingly stronger lines. Since $W_0$ in saturated absorption lines is an indicator of the velocity spread of the absorbing clouds, we interpret this as an evolution in the kinematic properties of galaxies from moderate to low z.Comment: 50 pages, 26 figures, accepted for publication in Ap

On integration of the Kowalevski gyrostat and the Clebsch problems

For the Kowalevski gyrostat change of variables similar to that of the Kowalevski top is done. We establish one to one correspondence between the Kowalevski gyrostat and the Clebsch system and demonstrate that Kowalevski variables for the gyrostat practically coincide with elliptic coordinates on sphere for the Clebsch case. Equivalence of considered integrable systems allows to construct two Lax matrices for the gyrostat using known rational and elliptic Lax matrices for the Clebsch model. Associated with these matrices solutions of the Clebsch system and, therefore, of the Kowalevski gyrostat problem are discussed. The Kotter solution of the Clebsch system in modern notation is presented in detail.Comment: LaTeX, 24 page

Thoracic duct fistula and renal transplantation

Thoracic duct drainage (TDD) was established for 21-115 days in 40 kidney recipients with an average removal per patient day of 4.7 1 lymph and 1.88 billion cells. Cellular and humoral immunity were depressed. TDD and immunosuppressive drugs were started at transplantation in 35 recipients of cross-match negative grafts. Although the results were better than in precedent non-TDD controls, eight patients rejected their grafts before a full TDD effect, and three of the eight developed predominantly anti-B lymphocyte cytotoxic antibodies which were probably responsible for positive cross-matches with their next donors. With continuing TDD, all eight patients had good initial function after early retransplantation. In five more 'nontransplantable' patients with performed cytotoxic antibodies, TDD was started 30-56 days before transplantation. In these five pretreated patients, antibodies persisted with positive antidonor cross-matches. Hyperacute rejection occurred repeatedly in two patients with high anti-T (and anti-B) titers, but was surmounted in three patients with lower titers. From the clinical and immunologic data, we have concluded that TDD should be used for pretreatment of all cases with or without prior antibodies, and have suggested an adjustable management plan that takes into account new developments in antibody monitoring

On Foundation of the Generalized Nambu Mechanics

We outline the basic principles of canonical formalism for the Nambu mechanics---a generalization of Hamiltonian mechanics proposed by Yoichiro Nambu in 1973. It is based on the notion of Nambu bracket which generalizes the Poisson bracket to the multiple operation of higher order $n \geq 3$ on classical observables and is described by Hambu-Hamilton equations of motion given by $n-1$ Hamiltonians. We introduce the fundamental identity for the Nambu bracket which replaces Jacobi identity as a consistency condition for the dynamics. We show that Nambu structure of given order defines a family of subordinated structures of lower order, including the Poisson structure, satisfying certain matching conditions. We introduce analogs of action from and principle of the least action for the Nambu mechanics and show how dynamics of loops ($n-2$-dimensional objects) naturally appears in this formalism. We discuss several approaches to the quantization problem and present explicit representation of Nambu-Heisenberg commutation relation for $n=3$ case. We emphasize the role higher order algebraic operations and mathematical structures related with them play in passing from Hamilton's to Nambu's dynamical picture.Comment: 27 page

On compression of Bruhat-Tits buildings

We obtain an analog of the compression of angles theorem in symmetric spaces for Bruhat--Tits buildings of the type $A$. More precisely, consider a $p$-adic linear space $V$ and the set $Lat(V)$ of all lattices in $V$. The complex distance in $Lat(V)$ is a complete system of invariants of a pair of points of $Lat(V)$ under the action of the complete linear group. An element of a Nazarov semigroup is a lattice in the duplicated linear space $V\oplus V$. We investigate behavior of the complex distance under the action of the Nazarov semigroup on the set $Lat(V)$.Comment: 6 page