Microfluidic multi-analyte gradient generator

A microfluidic device was developed to produce temporal concentration gradients of multiple analytes. Four on-chip pumps delivered pulses of three analytes and buffer to a 14-cm channel where the pulses were mixed to homogeneity. The final concentration of each analyte was dependent on the temporal density of the pulses from each pump. The concentration of each analyte was varied by changing the number of pump cycles from each reservoir while maintaining the total number of pump cycles per unit time to ensure a constant total flow rate in the device. To gauge the independent nature of each pump, sinusoidal waves of fluorescein concentration were produced from each pump with independent frequencies and amplitudes. The resulting fluorescence intensity was compared with a theoretical summation of the waves and the experimental data matched the theoretical waves within 1%, indicating that the pumps were operating independently and outputting the correct frequency and amplitude. The device was used to demonstrate the role of adenosine triphosphate-sensitive K⁺ channels in glucose-stimulated increases in intracellular [Ca²⁺] in islets of Langerhans. Perfusion of single islets of Langerhans with combinations of glucose, diazoxide, and K⁺ resulted in intracellular Ca²⁺ patterns similar to what has been observed using conventional perfusion devices. The system will be useful in other studies with islets of Langerhans, as well as other assays that require the modulation of multiple analytes in time.     

π‐Expanded α,β‐Unsaturated Ketones: Synthesis,Optical Properties,and Two‐Photon‐Induced Polymerization

A library of π‐expanded α,β‐unsaturated ketones was designed and synthesized. They were prepared by a combination of Wittig reaction, Sonogashira reaction, and aldol condensation. It was further demonstrated that the double aldol condensation can be performed effectively for highly polarized styrene‐ and diphenylacetylene‐derived aldehydes. The strategic placement of two dialkylamino groups at the periphery of D ‐π‐A‐π‐D molecules resulted in dyes with excellent solubility. These ketones absorb light in the region 400–550 nm. Many of them display strong solvatochromism so that the emission ranges from 530–580 nm in toluene to the near‐IR region in benzonitrile. Ketones based on cyclobutanone as central moieties display very high fluorescence quantum yields in nonpolar solvents, which decrease drastically in polar media. Photophysical studies of these new functional dyes revealed that they possess an enhanced two‐photon absorption cross section when compared with simpler ketone derivatives. Due to strong polarization of the resulting dyes, values of two‐photon absorption cross sections on the level of 200–300 GM at 800 nm were achieved, and thanks to that as well as the presence of the keto group, these new two‐photon initiators display excellent performance so that the operating region is 5–75 mW in some cases.     

Identification of Structure–Activity Relationships from Screening a Structurally Compact DNA‐Encoded Chemical Library

Methods for the rapid and inexpensive discovery of hit compounds are essential for pharmaceutical research and DNA‐encoded chemical libraries represent promising tools for this purpose. We here report on the design and synthesis of DAL‐100K, a DNA‐encoded chemical library containing 103 200 structurally compact compounds. Affinity screening experiments and DNA‐sequencing analysis provided ligands with nanomolar affinities to several proteins, including prostate‐specific membrane antigen and tankyrase 1. Correlations of sequence counts with binding affinities and potencies of enzyme inhibition were observed and enabled the identification of structural features critical for activity. These results indicate that libraries of this type represent a useful source of small‐molecule binders for target proteins of pharmaceutical interest and information on structural features important for binding.     

Location-domination in line graphs

A set $D$ of vertices of a graph $G$ is locating if every two distinct vertices outside $D$ have distinct neighbors in $D$; that is, for distinct vertices $u$ and $v$ outside $D$, $N\left(u\right)\cap D\ne N\left(v\right)\cap D$, where $N\left(u\right)$ denotes the open neighborhood of $u$. If $D$ is also a dominating set (total dominating set), it is called a locating-dominating set (respectively, locating-total dominating set) of $G$. A graph $G$ is twin-free if every two distinct vertices of $G$ have distinct open and closed neighborhoods. It is conjectured (Garijo et al., 2014 [15]) and (Foucaud and Henning, 2016 [12]) respectively, that any twin-free graph $G$ without isolated vertices has a locating-dominating set of size at most one-half its order and a locating-total dominating set of size at most two-thirds its order. In this paper, we prove these two conjectures for the class of line graphs. Both bounds are tight for this class, in the sense that there are infinitely many connected line graphs for which equality holds in the bounds.     

Ab initio spectroscopic study for the NaRb molecule in ground and excited states

A wide adiabatic study is performed for NaRb molecule, involving 15¹Σ⁺ electronic states including the ionic state Na^?Rb⁺, as well as 14³Σ⁺, 1–9^1,3Π, and 1–5^1,3Δ states. This investigation is performed using an ab initio approach which involves the effective core potential, the core polarization potential with l‐dependent cut‐off functions. The NaRb system has been treated as a two‐electron system and the full valence configuration interaction is easily achieved. The spectroscopic constants R_e, D_e, T_e, ω_e, ω_ex_e, B_e, and D₀ for all these states are derived. We have also computed the vibrational levels as well their spacing for different values of J. In addition, permanent and transition dipole moments are determined and analyzed. The Dunham coefficients have been used to perform experimental spacing to compare directly with our results. The present calculations on NaRb extend previous theoretical works to numerous electronic excited states in the various symmetries. © 2014 Wiley Periodicals, Inc.     

Differentiating a diverse range of volatile organic compounds with polyfluorophore sensors built on a DNA scaffold

Oligodeoxyfluorosides (ODFs) are short DNA-like oligomers in which DNA bases are replaced with fluorophores. A preliminary study reported that some sequences of ODFs were able to respond to a few organic small molecules in the vapor phase, giving a change in fluorescence. Here, we follow up on this finding by investigating a larger range of volatile organic analytes, and a considerably larger set of sensors. A library of tetramer ODFs of 2401 different sequences was prepared by using combinatorial methods, and was screened in air for fluorescence responses to a set of ten different volatile organics, including multiple aromatic and aliphatic compounds, acids and bases, varied functional groups, and closely related structures. Nineteen responding sensors were selected and characterized. These sensors were cross-screened against all ten analytes, and responses were measured qualitatively (by changes in color and intensity) and quantitatively (by measuring ΔR, ΔG, and ΔB values averaged over five to six sensor beads; R=red, G=green, B=blue). The results show that sensor responses were diverse, with a single sensor responding differently to as many as eight of the ten analytes; multiple classes of responses were seen, including quenching, lighting-up, and varied shifts in wavelength. Responses were strong, with raw ΔR, ΔG, and ΔB values of as high as >200 on a 256-unit scale and unamplified changes in many cases apparent to the naked eye. Sensors were identified that could distinguish clearly between even very closely related compounds such as acrolein and acrylonitrile. Statistical methods were applied to select a small set of four sensors that, as a pattern response, could distinguish between all ten analytes with high confidence. Sequence analysis of the full set of sensors suggested that sequence/order of the monomer components, and not merely composition, was highly important in the responses.     

Fast characterization of functionalized silica materials by silicon-29 surface-enhanced NMR spectroscopy using dynamic nuclear polarization

We demonstrate fast characterization of the distribution of surface bonding modes and interactions in a series of functionalized materials via surface-enhanced nuclear magnetic resonance spectroscopy using dynamic nuclear polarization (DNP). Surface-enhanced silicon-29 DNP NMR spectra were obtained by using incipient wetness impregnation of the sample with a solution containing a polarizing radical (TOTAPOL). We identify and compare the bonding topology of functional groups in materials obtained via a sol-gel process and in materials prepared by post-grafting reactions. Furthermore, the remarkable gain in time provided by surface-enhanced silicon-29 DNP NMR spectroscopy (typically on the order of a factor 400) allows the facile acquisition of two-dimensional correlation spectra.     

On melting dynamics and the glass transition. I. Glassy aspects of melting dynamics

The following properties are in the present literature associated with the behavior of supercooled glass-forming liquids: faster than exponential growth of the relaxation time, dynamical heterogeneities, growing point-to-set correlation length, crossover from mean-field behavior to activated dynamics. In this paper we argue that these properties are also present in a much simpler situation, namely the melting of the bulk of an ordered phase beyond a first order phase transition point. This is a promising path toward a better theoretical, numerical and experimental understanding of the above phenomena and of the physics of supercooled liquids. We discuss in detail the analogies and the differences between the glass and the bulk melting transitions.     

Optimizing the formation of biocompatible gold nanorods for cancer research: functionalization, stabilization and purification

We have investigated the most efficient way of preparing biocompatible gold nanorods (GNR) used as tool for cancer imaging and therapy. The surface of cetyltrimethylammonium bromide-stabilized gold nanorods (GNR-CTAB) was functionalized with various thio-polyethylene glycols of the general formula HS-PEGmX (m=356-10,000; X=-OMe, -NH(2)). The influence of several parameters such as PEG chain length, reaction conditions and purification method on long-term stability, morphology and optical properties of the produced GNR-S-PEGmX was studied, demonstrating the existence of a threshold HS-PEGmX chain length (with molecular weight m≥2000) for efficient steric stabilization of GNR. Several purification techniques were compared: dialysis, centrifugation and a rarely used technique in this field, size exclusion chromatography. While a very weak efficiency of dialysis was evidenced, both centrifugation and size exclusion chromatography were found to provide pure GNRs, though the latter method yielded nanoparticles with a significantly higher stability. Finally, the long-term stability of the produced GNRs was investigated in various media: water, PBS buffer and serum.