Engineering Protein Venoms as Self-Assembling CXCR4-Targeted Cytotoxic Nanoparticles

Protein venoms are effective cytotoxic molecules that when conveniently targeted to tumoral markers can be exploited as promising anticancer drugs. Here, it is explored whether the structurally unrelated melittin, gomesin, and CLIP71 could be functionally active when engineered, in form of GFP fusions, as self-assembling multimeric nanoparticles. Incorporated in modular constructs including a C-terminal polyhistidine tag and an N-terminal peptidic ligand of the cytokine receptor CXCR4 (overexpressed in more than 20 human neoplasias), these venoms are well produced in recombinant bacteria as proteolytically stable regular nanoparticles ranging between 12 and 35 nm. Being highly fluorescent, these materials selectively penetrate, label, and kill CXCR4⁺ tumor cells in a CXCR4-dependent fashion. The obtained data support the concept of recombinant venoms as promising drugs, through the precise formulation as tumor-targeted nanomaterials for selective theragnostic applications in CXCR4⁺ cancers.     

Comparison of water isotope-ratio determinations using two cavity ring-down instruments and classical mass spectrometry in continuous ice-core analysis

We present a detailed comparison between subsequent versions of commercially available wavelength-scanned cavity ring-down water isotope analysers (L2120-i and L2130-i, Picarro Inc.). The analysers are used in parallel in a continuous mode by adaption of a low-volume flash evaporation module. Application of the analysers to ice-core analysis is assessed by comparison between continuous water isotope measurements of a glacial ice-core from Severnaya Zemlya with discrete isotope-ratio mass spectrometry measurements performed on parallel samples from the same ice-core. The great advances between instrument versions, particularly in the measurement of δ²H, allow the continuous technique to achieve the same high level of accuracy and precision obtained using traditional isotope spectrometry techniques in a fraction of the experiment time. However, when applied to continuous ice-core measurements, increased integration times result in a compromise of the achievable depth resolution of the ice-core records.     

Managing contribution and capital market risk in a funded public defined benefit plan: Impact of CVaR cost constraints

Using a Monte Carlo framework, we analyze the risks and rewards of moving from an unfunded defined benefit pension system to a funded plan for German civil servants, allowing for alternative strategic contribution and investment patterns. In the process we integrate a Conditional Value at Risk (CVaR) restriction on overall plan costs into the pension manager’s objective of controlling contribution rate volatility. After estimating the contribution rate that would fully fund future benefit promises for current and prospective employees, we identify the optimal contribution and investment strategy that minimizes contribution rate volatility while restricting worst-case plan costs. Finally, we analyze the time path of expected and worst-case contribution rates to assess the chances of reduced contribution rates for current and future generations. Our results show that moving toward a funded public pension system can be beneficial for both civil servants and taxpayers.     

Global homeomorphisms and covering projections on metric spaces

For a large class of metric spaces with nice local structure, which includes Banach–Finsler manifolds and geodesic spaces of curvature bounded above, we give sufficient conditions for a local homeomorphism to be a covering projection. We first obtain a general condition in terms of a path continuation property. As a consequence, we deduce several conditions in terms of path- liftings involving a generalized derivative, and in particular we obtain an extension of Hadamard global inversion theorem in this context. Next we prove that, in the case of quasi-isometric mappings, some of these sufficient conditions are also necessary. Finally, we give an application to the existence of global implicit functions. O. Gutú and J. A. Jaramillo were supported in part by D.G.E.S. (Spain) Grant BFM2003-06420.     

Asymptotic properties of solutions to some nonlinear integral equations of convolution type

For a class of nonlinear integral equations of convolution type we give necessary and sufficient conditions for the boundedness of nonnegative solutions. Moreover, conditions for the solution to converge asymptotically to a determined limit are obtained.     

Generalizations of some conjectures of Sun on the relations between N(a, b, c, d; n) and T(a, b, c, d; n)

The Ramanujan Journal - We derive some new finite sums involving the sequence $$s_{2}\left( n\right) ,$$ the sum-of-digits of the expansion of n in base 2. These functions allow us to generalize...     

Some modular relations for Ramanujan’s function k(q)=r(q)r^2(q^2)

In both his second and lost notebooks, Ramanujan introduced and studied a function \(k(q)=r(q)r^2(q^2)\) , where \(r(q)\) is the Rogers–Ramanujan continued fraction. Ramanujan also recorded five beautiful relations between the Rogers–Ramanujan continued fraction \(r(q)\) and the five continued fractions \(r(-q)\) , \(r(q^2)\) , \(r(q^3)\) , \(r(q^4)\) , and \(r(q^5)\) . Motivated by those relations, we present some modular relations between \(k(q)\) and \(k(-q)\) , \(k(-q^2)\) , \(k(q^3)\) , and \(k(q^5)\) in this paper.     

Global inversion theorems via coercive functionals on metric spaces

Let X$X$ and Y$Y$ be metric spaces. We give sufficient metric conditions for a local homeomorphism f:X→Y$f:X\to Y$ to be a global one. We achieve this by means of auxiliary coercive functionals; several expected global inversion theorems are obtained by choosing different functionals.     

Electrochemical behavior of the tris(pyridine)-Cu funnel complexes: an overall induced-fit process involving an entatic state through a supramolecular stress

The electrochemical behavior of the tris(pyridine) calix[6]arene Cu adducts is unique as compared to that of most classical Cu complexes in a strain-free environment. The presence of MeCN buried inside the cavity is a prerequisite for a quasi-reversible behavior in a dynamic mode. The CV behavior assisted by simulation outlines that the coordination adaptability of the Cu(II)/Cu(I) redox states is completely reversed, with a Td geometry enforced at either redox states. Hence, the supramolecular control of the Cu coordination by a protein-like pocket determines the dynamics of the electron transfer process, its thermodynamics, and the kinetics of the reorganizational barrier and generates a preorganized state for oxidation. This redox behavior corresponds to an overall induced-fit process generating a truly entatic highly oxidizing Cu(II) state through a protein-like strain by involvement of the secondary coordination sphere.