Analysis of the effect of an electric-field profile on the gain bandwidth product of avalanche photodetectors

We investigate the effect of the electric-field profile on the gain-bandwidth product of avalanche photodetectors with separate absorption and multiplication. We show that for a given multiplication layer thickness the electric-field profile plays an important role in determining the gain-bandwidth product. The calculation results show that an increasing triangular electric-field profile yields a larger gain-bandwidth product than most other profiles for Si/InGaAs avalanche photodetectors.     

Synthesis,spectroscopic characterization and DFT study of dinuclear ruthenium sawhorse-type complexes derived from the reaction of trinuclear aggregates and (Z)-5-arylidenerhodanines

The synthesis of dinuclear ruthenium sawhorse-type complexes [Ru₂(μ-ArCH:Rhod)₂(CO)₄]_n 12a–e and [Ru₂(ArCH:Rhod)₂(μ-ArCH:Rhod)₂(CO)₄] 13a–e through reaction of [Ru₃(CO)₁₀(NCMe)₂] and [Ru₃(CO)₁₂] and the corresponding (Z)-5-arylidenerhodanines (ArCH:Rhod) 10a–e, respectively, are reported. These complexes are arranged in a sawhorse structure in which two bridged (Z)-5-arylidenerhodanines coordinate to the metals using sulfur and nitrogen of the rhodanine ring. A Density Functional Theory method was used to gain insight into the polymerization process by calculating dimerization Gibbs energies (ΔG_dim). Values between ?10.7 and ?5.3 kcal mol^?1 indicate that dimerization is a spontaneous process. A reaction pathway for formation of the sawhorse compounds [Ru₂(μ-ArCH:Rhod)₂(CO)₄] was calculated and the rate-determining step for the mechanism is coordination of a second (Z)-5-arylidenerhodanine ligand with activation energies between 41.1 and 47.8 kcal mol^?1. In order to understand the apparent thermodynamic favorability of the fragmentation step, we calculated the fragmentation energy (ΔE_Frag) for the key intermediate and its energetic contributors, the interaction energy, ΔE_int and the reorganization energy, ΔE_reorg. Low values of ΔE_Frag imply that the fragmentation is thermodynamically facile. Large values of ΔE_int are countered by opposite and large values of ΔE_reorg which indicate that the cleavage of the trimetallic intermediate aggregate is determined by the nature of the ligand and the balance between its interaction with the metal and the extent of structural reorganization.     

Back-electron transfer suppresses the periodic length dependence of DNA-mediated charge transport across adenine tracts

DNA-mediated charge transport (CT) is exquisitely sensitive to the integrity of the bridging pi-stack and is characterized by a shallow distance dependence. These properties are obscured by poor coupling between the donor/acceptor pair and the DNA bridge, or by convolution with other processes. Previously, we found a surprising periodic length dependence for the rate of DNA-mediated CT across adenine tracts monitored by 2-aminopurine fluorescence. Here we report a similar periodicity by monitoring N 2-cyclopropylguanosine decomposition by rhodium and anthraquinone photooxidants. Furthermore, we find that this periodicity is attenuated by consequent back-electron transfer (BET), as observed by direct comparison between sequences that allow and suppress BET. Thus, the periodicity can be controlled by engineering the extent of BET across the bridge. The periodic length dependence is not consistent with a periodicity predicted by molecular wire theory but is consistent with a model where multiples of four to five base pairs form an ideal CT-active length of a bridging adenine domain.     

Rerouting the folding pathway of the Notch ankyrin domain by reshaping the energy landscape

The modular nature of repeat proteins has made them a successful target for protein design. Ankyrin repeat, TPR, and leucine rich repeat domains that have been designed solely on consensus information have been shown to have higher thermostability than their biological counterparts. We have previously shown that we can reshape the energy landscape of a repeat protein by adding multiple C-terminal consensus ankyrin repeats to the five N-terminal repeats of the Notch ankyrin domain. Here we explore how the folding mechanism responds to reshaping of the energy landscape. We have used analogous substitutions of a conserved alanine with glycine in each repeat to determine the distribution of structure in the transition state ensembles of constructs containing one (Nank1-5C1) and two consensus (Nank1-5C2) ankyrin repeats. Whereas folding of the wild-type Notch ankyrin domain is slowed by substitutions in its central repeats, (1) folding of Nank1-5C1 and Nank1-5C2 is slowed by substitutions in the C-terminal repeats. Thus, the addition of C-terminal stabilizing repeats shifts the transition state ensemble toward the C-terminal repeats, rerouting the folding pathway of the ankyrin repeat domain. These findings indicate that, for the Notch ankyrin domain, folding pathways are selected based on local energetics.     

Counterions influence reactivity of metal ions with cysteinyldopa model compounds

Cysteinyldopas are naturally occurring conjugates of cysteine and dopa (3,4-dihydroxy-l-phenylalanine) that are precursors to red pheomelanin pigments. Metal ions are known to influence pheomelanogenesis in vitro and may be regulatory factors in vivo. Cydo (3-[(2-amino-ethyl)sulfanyl]-4,6-di-tert-butylbenzene-1,2-diol) and CarboxyCydo (2-amino-3-(4,6-di-tert-butyl-2,3-dihydroxyphenylsulfanyl)-propionic acid) are model compounds of cysteinyldopa that retain its metal-binding functionalities but cannot polymerize due to the presence of blocking tert-butyl groups. Cydo reacts readily with zinc(II) acetate or nickel(II) acetate to form a cyclized 1,4-benzothiazine (zine) intermediate that undergoes ring contraction to form benzothiazole (zole) unless it is stabilized by coordination to a metal ion. The crystal structure of [Ni(zine)2] is reported. The acetate counteranion is required for the zinc-promoted reactivity, as neither zinc(II) sulfate nor zinc(II) chloride alone promotes the transformation. The counterion is less important for redox-active copper and iron, which both readily promote the oxidation of Cydo to zine and zole species; Cu(II) complexes of both zine and zole have been characterized by X-ray crystallography. In the case of CarboxyCydo, a 3-carboxy-1,4-benzothiazine intermediate decarboxylates to form [Cu(zine)2] under basic conditions, but in the absence of base forms a mixture of products that includes the carboxylated dimer 2,2'-bibenzothiazine (bi-zine). These products are consistent with species implicated in the pheomelanogenesis biosynthetic pathway and emphasize how metal ions, their counteranions, and reaction conditions can alter pheomelanin product distribution.     

Hofmeister Effects of Group II Cations as Seen in the Unfolding of Ribonuclease A

This work studies the effects of alkaline-earth cation addition on the unfolding free energy of a model protein, pancreatic Ribonuclease A (RNase A) by differential scanning calorimetry analysis. RNase A was chosen because: a) it does not specifically bind Mg²⁺, Ca²⁺ and Sr²⁺ cations and b) maintains its structural integrity throughout a large pH range. We have measured and compared the effects of NaCl, MgCl₂, CaCl₂ and SrCl₂ addition on the melting point of RNase A. Our results show that even though the addition of group II cations to aqueous solvent reduces the solubility of nonpolar residues (and enhances the hydrophobic effect), their interactions with the amide moieties are strong enough to “salt-them-in” the solvent, thereby causing an overall protein stability reduction. We demonstrate that the amide-cation interactions are a major contributor to the observed “Hofmeister Effects” of group II cations in protein folding. Our analysis suggests that protein folding “Hofmeister Effects” of group II cations, are mostly the aggregate sum of how cation addition simultaneously salts-out hydrophobic moieties by increasing the cavitation free energy, while promoting the salting-in of amide moieties through contact pair formation.     

In Situ Ellipsometry Measurements on the Halide Phase Segregation of Mixed Halide Lead Perovskites**

Methylammonium lead iodide bromides MAPb(Br_xI_1-x)₃ are a class of mixed halide lead perovskites, materials that offer high-power conversion efficiencies and bandgap tunability. For these reasons, they are a promising absorber material for future solar cells, although their use is still limited due to several factors. The reversible phase segregation under even low light intensities is one of them, lowering the effective bandgap due to local segregation into iodide-rich and bromide-rich phases. While several studies have been done to illuminate the mechanism and suppression of phase segregation, challenges remain to understand its kinetics. We obtained dynamic ellipsometric measurements from x=0.5 mixed halide lead perovskite thin films protected by a polystyrene layer under green laser light with a power density of ∼11 W/cm². Time constants between 1.7(±0.7)×10⁻³ s⁻¹ for the segregation and 1.5(±0.6)×10⁻⁴ s⁻¹ for recovery were calculated. The phase segregation rate constants are surprisingly two orders of magnitude slower than and the recovery rate is consistent with those measured using photoluminescence methods under similar conditions. These results confirm a concern in the literature about the complexity in the phase separation kinetics measured from photoluminescence. We expect ellipsometry to serve as a complementary technique to other spectroscopies in studying mixed-halide lead perovskites phase segregation in the future.     

[89Zr]-Pertuzumab PET Imaging Reveals Paclitaxel Treatment Efficacy Is Positively Correlated with HER2 Expression in Human Breast Cancer Xenograft Mouse Models

Paclitaxel (PTX) treatment efficacy varies in breast cancer, yet the underlying mechanism for variable response remains unclear. This study evaluates whether human epidermal growth factor receptor 2 (HER2) expression level utilizing advanced molecular positron emission tomography (PET) imaging is correlated with PTX treatment efficacy in preclinical mouse models of HER2+ breast cancer. HER2 positive (BT474, MDA-MB-361), or HER2 negative (MDA-MB-231) breast cancer cells were subcutaneously injected into athymic nude mice and PTX (15 mg/kg) was administrated. In vivo HER2 expression was quantified through [⁸⁹Zr]-pertuzumab PET/CT imaging. PTX treatment response was quantified by [¹⁸F]-fluorodeoxyglucose ([¹⁸F]-FDG) PET/CT imaging. Spearman’s correlation, Kendall’s tau, Kolmogorov–Smirnov test, and ANOVA were used for statistical analysis. [⁸⁹Zr]-pertuzumab mean standard uptake values (SUV_mean) of BT474 tumors were 4.9 ± 1.5, MDA-MB-361 tumors were 1.4 ± 0.2, and MDA-MB-231 (HER2−) tumors were 1.1 ± 0.4. [¹⁸F]-FDG SUV_mean changes were negatively correlated with [⁸⁹Zr]-pertuzumab SUV_mean (r = −0.5887, p = 0.0030). The baseline [¹⁸F]-FDG SUV_mean was negatively correlated with initial [⁸⁹Zr]-pertuzumab SUV_mean (r = −0.6852, p = 0.0002). This study shows PTX treatment efficacy is positively correlated with HER2 expression level in human breast cancer mouse models. Molecular imaging provides a non-invasive approach to quantify biological interactions, which will help in identifying chemotherapy responders and potentially enhance clinical decision-making.     

Development of saw palmetto (Serenoa repens) fruit and extract standard reference materials

As part of a collaboration with the National Institutes of Health’s Office of Dietary Supplements and the Food and Drug Administration’s Center for Drug Evaluation and Research, the National Institute of Standards and Technology has developed two standard reference materials (SRMs) representing different forms of saw palmetto (Serenoa repens), SRM 3250 Serenoa repens fruit and SRM 3251 Serenoa repens extract. Both of these SRMs have been characterized for their fatty acid and phytosterol content. The fatty acid concentration values are based on results from gas chromatography with flame ionization detection (GC-FID) and mass spectrometry (GC/MS) analysis while the sterol concentration values are based on results from GC-FID and liquid chromatography with mass spectrometry analysis. In addition, SRM 3250 has been characterized for lead content, and SRM 3251 has been characterized for the content of β-carotene and tocopherols. SRM 3250 (fruit) has certified concentration values for three phytosterols, 14 fatty acids as triglycerides, and lead along with reference concentration values for four fatty acids as triglycerides and 16 free fatty acids. SRM 3251 (extract) has certified concentration values for three phytosterols, 17 fatty acids as triglycerides, β-carotene, and γ-tocopherol along with reference concentration values for three fatty acids as triglycerides, 17 fatty acids as free fatty acids, β-carotene isomers, and δ-tocopherol and information values for two phytosterols. These SRMs will complement other reference materials currently available with concentrations for similar analytes and are part of a series of SRMs being developed for dietary supplements. Contribution of the US Government; not subject to copyright     

Fourier transform infrared studies in hypergolic ignition of ionic liquids

A class of room-temperature ionic liquids (RTILs) that exhibit hypergolic activity toward fuming nitric acid is reported. Fast ignition of dicyanamide ionic liquids when mixed with nitric acid is contrasted with the reactivity of the ionic liquid azides, which show high reactivity with nitric acid, but do not ignite. The reactivity of other potential salt fuels is assessed here. Rapid-scan, Fourier transform infrared (FTIR) spectroscopy of the preignition phase indicates the evolution of N 2O from both the dicyanamide and azide RTILs. Evidence for the evolution of CO 2 and isocyanic acid (HNCO) with similar temporal behavior to N 2O from reaction of the dicyanamide ionic liquids with nitric acid is presented. Evolution of HN 3 is detected from the azides. No evolution of HCN from the dicyanamide reactions was detected. From the FTIR observations, biuret reaction tests, and initial ab initio calculations, a mechanism is proposed for the formation of N 2O, CO 2, and HNCO from the dicyanamide reactions during preignition.