Directed formation of micro- and nanoscale patterns of functional light-harvesting LH2 complexes

The precision placement of the desired protein components on a suitable substrate is an essential prelude to any hybrid "biochip" device, but a second and equally important condition must also be met: the retention of full biological activity. Here we demonstrate the selective binding of an optically active membrane protein, the light-harvesting LH2 complex from Rhodobacter sphaeroides, to patterned self-assembled monolayers at the micron scale and the fabrication of nanometer-scale patterns of these molecules using near-field photolithographic methods. In contrast to plasma proteins, which are reversibly adsorbed on many surfaces, the LH2 complex is readily patterned simply by spatial control of surface polarity. Near-field photolithography has yielded rows of light-harvesting complexes only 98 nm wide. Retention of the native optical properties of patterned LH2 molecules was demonstrated using in situ fluorescence emission spectroscopy.     

A rotaxane mimic of the photoactive yellow protein chromophore environment: effects of hydrogen bonding and mechanical interlocking on a coumaric amide derivative

Hydrogen bonding in a [2]rotaxane is shown to stabilise the phenolate anion of a coumaric amide chromophore by almost 3 pKa units; however, the effect on the UV spectral shift in the anion is small and, significantly given the photochemistry of PYP, despite the hydrogen bonding olefin photoisomerisation in the anionic rotaxane remains heavily suppressed.     

Linear-scaling symmetric square-root decomposition of the overlap matrix

We present a robust linear-scaling algorithm to compute the symmetric square-root or Lowdin decomposition of the atomic-orbital overlap matrix. The method is based on Newton-Schulz iterations with a new approach to starting matrices. Calculations on 12 chemically and structurally diverse molecules demonstrate the efficiency and reliability of the method. Furthermore, the calculations show that linear scaling is achieved.     

Effects of hyperthermia on bioenergetic status and phosphorus T1S in human melanoma xenografts monitored by 31P-MRS.

Conventional hyperthermia enhances tumor response to radiotherapy through thermal cell inactivation and vascular shut-down, whereas mild hyperthermia potentiates the effect of radiotherapy by improving tumor oxygenation. The work reported here was aimed at investigating whether 31P-magnetic resonance spectroscopy (31P-MRS) measurements of tumor bioenergetic status; i.e., the (PCr + NTPbeta)/Pi resonance ratio, and/or the spin lattice relaxation times, T1s, of the Pi and NTPbeta resonances can be used to distinguish between the effects of conventional and mild hyperthermia. BEX-t human melanoma xenografts were treated at 43.0 degrees C for 15 or 60 min, and bioenergetic status and T1s were measured as function-of-time after treatment. Hyperthermia-induced effects on tumor blood flow was measured by using the 86Rb uptake method. The morphology of the capillary network in treated and untreated tumors was studied by histologic examination. Tumors treated for 15 min showed increased blood flow and dilated capillaries, whereas tumors treated for 60 min showed decreased blood flow and capillary occlusions; i.e., 43.0 degrees C for 15 min was a treatment consistent with mild hyperthermia and 43.0 degrees C for 60 min was consistent with conventional hyperthermia treatment of BEX-t tumors. Bioenergetic status increased after treatment at 43.0 degrees C for 15 min, and decreased after treatment at 43.0 degrees C for 60 min, similar to the blood flow. Likewise, the T1 of the Pi resonance increased after treatment at 43.0 degrees C for 15 min, and decreased after treatment at 43.0 degrees C for 60 min. The T1 of the NTPbeta resonance showed a similar change as the T1 of the Pi resonance, but less pronounced. Consequently, 31P-MRS measurements of tumor bioenergetic status and the T1 of the Pi resonance may perhaps be utilized to distinguish between vascular effects of mild and conventional hyperthermia.     

T3P-Promoted Synthesis of a Series of 2-Aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones and Their Activity against the Kinetoplastid Parasite Trypanosoma brucei

A series of fourteen 2-aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones was prepared at room temperature by T3P-mediated cyclization of N-phenyl-C-aryl imines with thionicotinic acid, two difficult substrates. The reactions were operationally simple, did not require specialized equipment or anhydrous solvents, could be performed as either two or three component reactions, and gave moderate–good yields as high as 63%. This provides ready access to N-phenyl compounds in this family, which have been generally difficult to prepare. As part of the study, the first crystal structure of neutral thionicotinic acid is also reported, and showed the molecule to be in the form of the thione tautomer. Additionally, the synthesized compounds were tested against T. brucei, the causative agent of Human African Sleeping Sickness. Screening at 50 µM concentration showed that five of the compounds strongly inhibited growth and killed parasites.     

QCD exotics

I review first some theoretical motivations for violation of Lorentz and/or CPT Invariance. Although the latter symmetries may be violated in a quantum gravity setting, nevertheless there are situations in which these violations are due to a given classical background geometry that may characterised early epochs of our Universe, and in fact be responsible for the observed dominance of matter over antimatter in the Universe. In this way I estimate some of the coefficients of the Standard Model Extension (SME), which is a framework for a field theoretic study of such a breakdown of fundamental symmetries. Then I describe briefly some tests of these symmetries, giving emphasis in low-energy antiproton physics and electric dipole moment measurements, of interest to this conference. I also mention the rôle of entangled states of neutral mesons in providing independent measurements of T(ime reversal) and CP Violation, thus providing independent tests of CPT symmetry, as well as novel (“smoking-gun” type) tests of decoherence-induced CPT violation, which may characterise some models of quantum gravity.     

Design and Sensing Properties of a Self‐Assembled Supramolecular Oligomer

Supramolecular polymers are a class of macromolecules stabilized by weak non‐covalent interactions. These self‐assembled aggregates typically undergo stimuli‐induced reversible assembly and disassembly. They thus hold great promise as so‐called functional materials. In this work, we present the design, synthesis, and responsive behavior of a short supramolecular oligomeric system based on two hetero‐complementary subunits. These “monomers” consist of a tetrathiafulvalene‐functionalized calix[4]pyrrole (TTF‐C[4]P) and a glycol diester‐linked bis‐2,5,7‐trinitrodicyanomethylenefluorene‐4‐carboxylate (TNDCF), respectively. We show that when mixed in organic solvents, such as CHCl₃, CH₂ClCH₂Cl, and methylcyclohexane, supramolecular aggregation takes place to produce short oligomers stabilized by hydrogen bonding and donor–acceptor charge‐transfer (CT) interactions. The self‐associated materials were characterized by ¹H NMR and UV/Vis/NIR absorption spectroscopy, as well as by concentration‐ and temperature‐dependent absorption spectroscopy and dynamic light scattering (DLS) analyses of both the monomeric and oligomerized species. The self‐associated system produced from TTF‐C[4]P and TNDCF exhibits a concentration‐dependent aggregation behavior typical of supramolecular polymers. Further support for the proposed self‐assembly came from theoretical calculations. The fluorescence emitting properties of TNDCF are quenched under conditions that promote the formation of supramolecular aggregates containing TTF‐C[4]P and TNDCF. This quenching effect has been utilized as a probe for the detection of substrates in the form of anions (i.e., chloride) and nitroaromatic explosives (i.e., 1,3,5‐trinitrobenzene). Specifically, the addition of these substrates to mixtures of TTF‐C[4]P and TNDCF produced a fluorescence “turn‐on” response.     

Probing the Bioactive Conformation of an Archetypal Natural Product HDAC Inhibitor with Conformationally Homogeneous Triazole‐Modified Cyclic Tetrapeptides

Fooling enzymes with mock amides : Analogues of apicidin, a cyclic‐tetrapeptide inhibitor of histone deacetylase (HDAC), were designed with a 1,4‐ or 1,5‐disubstituted 1,2,3‐triazole in place of a backbone amide bond to fix the bond in question in either a trans‐like or a cis‐like configuration. Thus, the binding affinity of distinct peptide conformations (see picture) could be probed. One analogue proved in some cases to be superior to apicidin as an HDAC inhibitor.

     

A lower bound for the symbolic multifractal spectrum of a self-similar multifractal with arbitrary overlaps

By now the multifractal structure of self-similar measures satisfying the so-called Open Set Condition is well understood. However, if the Open Set Condition is not satisfied, then almost nothing is known. In this paper we prove a nontrivial lower bound for the symbolic multifractal spectrum of an arbitrary self-similar measure. We emphasize that we are considering arbitrary self-similar measures (and sets) which are not assumed to satisfy the Open Set Condition or similar separation conditions. Our results also have applications to self-similar sets which do not satisfy the Open Set Condition (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)