Taxol Inclusion Complexes with a Cyclodextrin Dimer: Possibilities to Detoxify Chemotherapeutics and to Target Drugs Specifically to Tumors?

The natural drug, paclitaxel (taxol), is highly effectiveas a tumor chemotherapeuticwith a low probability of inducing chemoresistance,but shows severe toxic side effectsat the therapeutic dose. How can this toxicitybe overcome? Here we report the synthesisof cyclodextrin dimers connected at thesecondary face by amide-bonded aliphatic spacers. The spacer length of one of the dimers referred to asdiβCD(2N-A4C5A4) or dimer 7cmatches the distance between the twobenzoic acid residues of paclitaxel. We investigated the physical inclusion of taxol into this dimer using the TNS-label competition method. Affinity constants with the dimer in comparison to free β-cyclodextrin are found to be of the order of 10⁷ l/mole.When included into the cyclodextrin dimer, the drug shows a considerable time delay of incorporation into human tumor cell cultures (OAT SCLC cells) or a total exclusion from the cells. This is the prerequisite to avoid intoxication of other organs of a patient. Possibilities are discussed to detoxify chemotherapeutics and to target their inclusioncomplexes specifically to tumors using specific biological signals.     

Triads, Flocks of Conics and Q -(5,q)

We show that if an ovoid of Q (4,q),q even, admits a flock of conics then that flock must be linear. It follows that an ovoid of PG (3,q),q even, which admits a flock of conics must be an elliptic quadric. This latter result is used to give a characterisation of the classical example Q ^-(5,q) among the generalized quadrangles T ₃( ), where is an ovoid of PG (3q) and q is even, in terms of the geometric configuration of the centres of certain triads.     

Structure in the classical knot concordance group

We provide new information about the structure of the abelian group of topological concordance classes of knots in $S^3$. One consequence is that there is a subgroup of infinite rank consisting entirely of knots with vanishing Casson-Gordon invariants but whose non-triviality is detected by von Neumann signatures.     

Groups with infinitely many types of fixed subgroups

It is a theorem of Shor that ifG is a word-hyperbolic group, then up to isomrphism, only finitely many groups appear as fixed subgroups of automorphisms ofG. We give an example of a groupG acting freely and cocompactly on a CAT(0) square complex such that infinitely many non-isomorphic groups appear as fixed subgroups of automorphisms ofG. Consequently, Shor’s finiteness result does not hold if the negative curvature condition is relaxed to either biautomaticity or nonpositive curvature. D. T. Wise was supported by grants from FCAR and NSERC.     

Free group representations from vector-valued multiplicative functions,I

Let Γ denote a noncommutative free group and let Ω stand for its boundary. We construct a large class of unitary representations of Γ. This class contains many previously studied representations, and is closed under several natural operations. Each of the constructed representations is in fact a representation of Γ ⋉_λ C(Ω). We prove here that each of them is irreducible as a representation of Γ ⋉_λ C(Ω). Actually, as will be shown in further work, each of them is irreducible as a representation of Γ, or is the direct sum of exactly two irreducible, inequivalent Γ-representations. This research was supported by the Italian CNR.     

Isoperimetric inequalities for nilpotent groups

We prove that every finitely generated nilpotent group of class c admits a polynomial isoperimetric function of degree c + 1 and a linear upper bound on its filling length function.     

A Class of Orthogonal Refinable Functions and Wavelets

We give a construction, for any n 2, of a space S of spline functions of degree n – 1 with simple knots in (1/4)Z which is generated by a triple of refinable, orthogonal functions with compact support. Indeed, the result holds more generally by replacing the B-spline of degree n – 1 with simple knots at the integers by any continuous refinable function whose mask is a Hurwitz polynomial of degree n. A simple construction is also given for the corresponding wavelets.     

Organizations and Complexity: Searching for the Edge of Chaos

Traditional organizational theory advocates increased differentiation and horizontal integration for organizations in unstable environments or with uncertain technologies. This paper seeks to develop a better understanding of the relationship of group structure and the level of interdependency between individuals on group performance under various task complexities. Complexity theory in general, and NK models in particular, are introduced as theoretical frameworks that offer an explanation for group performance. Simulation models are developed, based on the communication network research of Bavelas (1948) and Leavitt (1952), to explore the effects of decentralization and interdependence. The simulation model developed here shows general consistency with previous human subject experiments. However, contrary to predictions, not all decentralized group structures perform well when undertaking complex task assignments. Structures that are highly connected (actors communicating with all others) perform much worse than those with a lower level of connection. Further experiments varying both the number of actors and the degree of interdependence between them find evidence of the edge of chaos. This research advances our understanding of organizations beyond earlier models by suggesting that there is an optimal range of interconnectedness between actors or tasks that explains the variation in performance. An intriguing result is that this optimal level of interdependence is fairly low, regardless of the size of the group.     

Synthesis of SnO2−x nanoparticles tuned between 0 x 1 in a premixed low pressure H2/O2/Ar flame

The transition from tin monoxide to tin dioxide is investigated by doping a low pressure premixed H₂/O₂/Ar flame with dilute concentrations of tetramethyl tin (TMT) Sn(CH₃)₄. The H₂/O₂ ratio was varied between 1.97 and 0.97; the reactor pressure was set to 30 mbar. The inlet gas velocity was kept constant and the precursor concentration was varied between 200 and 700 ppm. Mean particle diameters between 3 nm d_p 7 nm were measured using a particle mass spectrometer (PMS), while X-ray diffraction (XRD) and transmission electron microscope (TEM) analysis revealed information on crystal structure as well as morphology of the synthesized oxides. A gray SnO film was observed in the reactor at low oxygen concentrations, while for higher oxygen concentrations light yellow sub-stoichiometric tin oxides and white SnO₂ were obtained. Further analysis of the sub-stoichiometric oxides, using atomic electron spectroscopy AES revealed that SnO_2−x (0.2 x 0.6) was obtained. Furthermore, electrical characterization of all materials, deposited on interdigital capacitors, showed a decrease in the conductivity of the nanoparticles with increasing oxidation (decreasing x).