Modification of Hemodialysis Membranes for Efficient Circulating Tumor Cell Capture for Cancer Therapy

Background: It is well known that more than 90% of cancer deaths are due to metastases. However, the entire tumorigenesis process is not fully understood, and it is evident that cells spreading from the primary tumor play a key role in initiating the metastatic process. Tumor proliferation and invasion also elevate the concentration of regular and irregular metabolites in the serum, which may alter the normal function of the entire human homeostasis and possibly causes cancer metabolism syndrome, also referred to as cachexia. Methods: We report on the modification of commercially available hemodialysis membranes to selectively capture circulating tumor cells from the blood stream by means of immobilized human anti-EpCAM antibodies on the inner surface of the fibers. All critical steps are described that required in situ addition of the immuno-affinity feature to hemodialyzer cartridges in order to capture EpCAM positive circulating tumor cells, which represents ~80% of cancer cell types. Results: The cell capture efficiency of the suggested technology was demonstrated by spiking HCT116 cancer cells both into buffer solution and whole blood and run through on the modified cartridge. Flow cytometry was used to quantitatively evaluate the cell clearance performance of the approach. Conclusions: The suggested modification has no significant effect on the porous structure of the hemodialysis membranes; it keeps its cytokine removal capability, addressing cachexia simultaneously with CTC removal.     

Thermodynamic, electrochemical, high-pressure kinetic, and mechanistic studies of the formation of oxo Fe(IV)-TAML species in water

Stopped-flow kinetic studies of the oxidation of Fe(III)-TAML catalysts, [ F e{1,2-X(2)C(6)H(2)-4,5-( NCOCMe(2) NCO)(2)CMe(2)}(OH(2))](-) (1), by t-BuOOH and H(2)O(2) in water affording Fe(IV) species has helped to clarify the mechanism of the interaction of 1 with primary oxidants. The data collected for substituted Fe(III)-TAMLs at pH 6.0-13.8 and 17-45 °C has confirmed that the reaction is first order both in 1 and in peroxides. Bell-shaped pH profiles of the effective second-order rate constants k(I) have maximum values in the pH range of 10.5-12.5 depending on the nature of 1 and the selected peroxide. The "acidic" part is governed by the deprotonation of the diaqua form of 1 and therefore electron-withdrawing groups move the lower pH limit of the reactivity toward neutral pH, although the rate constants k(I) do not change much. The dissection of k(I) into individual intrinsic rate constants k(1) ([FeL(OH(2))(2)](-) + ROOH), k(2) ([FeL(OH(2))OH)](2-) + ROOH), k(3) ([FeL(OH(2))(2)](-) + ROO(-)), and k(4) ([FeL(OH(2))OH)](2-) + ROO(-)) provides a model for understanding the bell-shaped pH-profiles. Analysis of the pressure and substituent effects on the reaction kinetics suggest that the k(2) pathway is (i) more probable than the kinetically indistinguishable k(3) pathway, and (ii) presumably mechanistically similar to the induced cleavage of the peroxide O-O bond postulated for cytochrome P450 enzymes. The redox titration of 1 by Ir(IV) and electrochemical data suggest that under basic conditions the reduction potential for the half-reaction [Fe(IV)L(=O)(OH(2))](2-) + e(-) + H(2)O → [Fe(III)L(OH)(OH(2))](2-) + OH(-) is close to 0.87 V (vs NHE).     

Structure-activity relationship of cyclic nitroxides as SOD mimics and scavengers of nitrogen dioxide and carbonate radicals

Synthetic nitroxide antioxidants attenuate oxidative damage in various experimental models. Their protective effect reportedly depends on ring size and ring substituents and is greater for nitroxides having lower oxidation potential. The present study focuses on the kinetics and mechanisms of the reactions of piperidine, pyrrolidine and oxazolidine nitroxides with HO2*/O2*-, *NO2 and CO3*- radicals, which are key intermediates in many inflammatory and degenerative diseases. It is demonstrated that nitroxides are the most efficient scavengers of *NO2 at physiological pH (k = (3-9) x 10(8) M(-1) s(-1)) and among the most effective metal-independent scavengers of CO3*- radicals (k = (2 - 6) x 10(8) M(-1) s(-1)). Their reactivity toward HO2*, though not toward *NO2 and CO3*-, depends on the nature of the ring side-chain and particularly on the ring-size. All nitroxide derivatives react slowly with O2*- and are relatively inefficient SOD mimics at physiological pH. Even piperidine nitroxides, having the highest SOD-like activity, demonstrate a catalytic activity of about 1000-fold lower than that of native SOD at pH 7.4. The present results do not indicate any correlation between the kinetics of HO2*/O2*-, *NO2 and CO3*- removal by nitroxides and their protective activity against biological oxidative stress and emphasize the importance of target-oriented nitroxides, i.e., interaction between the biological target and specific nitroxides.     

The Stirling Polynomial of a Simplicial Complex

We introduce a new encoding of the face numbers of a simplicial complex, its Stirling polynomial, that has a simple expression obtained by multiplying each face number with an appropriate generalized binomial coefficient. We prove that the face numbers of the barycentric subdivision of the free join of two CW-complexes may be found by multiplying the Stirling polynomials of the barycentric subdivisions of the original complexes. We show that the Stirling polynomial of the order complex of any simplicial poset and of certain graded planar posets has non-negative coefficients. By calculating the Stirling polynomial of the order complex of the r-cubical lattice of rank n + 1 in two ways, we provide a combinatorial proof for the following identity of Bernoulli polynomials:

Improving the Crossing Lemma by Finding More Crossings in Sparse Graphs

Twenty years ago, Ajtai et al. and, independently, Leighton discovered that the crossing number of any graph with v vertices and e > 4v edges is at least ce³/v², where c > 0 is an absolute constant. This result, known as the "Crossing Lemma," has found many important applications in discrete and computational geometry. It is tight up to a multiplicative constant. Here we improve the best known value of the constant by showing that the result holds with c > 1024/31827 > 0.032. The proof has two new ingredients, interesting in their own right. We show that (1) if a graph can be drawn in the plane so that every edge crosses at most three others, then its number of edges cannot exceed 5.5(v-2); and (2) the crossing number of any graph is at least Both bounds are tight up to an additive constant (the latter one in the range ).     

Ważewski theorem on time scales with a set of egress points that is not the whole boundary

In the paper the celebrated Wa?ewski retract method is developed for planar dynamic equations on an arbitrary time scale without a restrictive assumption that the whole boundary of a set of constraints, where we look for solutions, is a set of egress points. As a consequence, some recently published results are essentially generalized. One transparent example illustrating the main theorem is presented. The results are new and more general even for ordinary difference equations.     

Development of Palladium Surface‐Enriched Heteronuclear Au–Pd Nanoparticle Dehalogenation Catalysts in an Ionic Liquid

Heteronuclear Au–Pd nanoparticles were prepared and immobilized in the functionalized ionic liquid [C₂OHmim][NTf₂]. The structural and electronic properties of the nanoparticles were characterized by a range of techniques and the surface of the nanoparticles was found to be enriched in Pd. Moreover, the extent of Pd enrichment is easily controlled by varying the ratio of Au and Pd salts used in the synthesis. The heteronuclear nanoparticles were found to be effective catalysts in dehalogenation reactions with no activity observed for the pure Au nanoparticles and only limited activity for the pure Pd nanoparticles. The activity of the heteronuclear nanoparticles may be attributed to charge transfer from Pd to Au and consequently to more efficient reductive elimination.     

Pretty good quantum state transfer in asymmetric graphs via potential

We construct infinite families of graphs in which pretty good state transfer can be induced by adding a potential to the nodes of the graph (i.e. adding a number to a diagonal entry of the adjacency matrix). Indeed, we show that given any graph with a pair of cospectral nodes, a simple modification of the graph, along with a suitable potential, yields pretty good state transfer between the nodes. This generalizes previous work, concerning graphs with an involution, to asymmetric graphs.