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Millions of distinct metal-organic frameworks (MOFs) can be made by combining metal nodes and organic linkers. At present, over 90,000 MOFs have been synthesized and over 500,000 predicted. This raises the question whether a new experimental or predicted structure adds new information. For MOF chemists, the chemical design space is a combination of pore geometry, metal nodes, organic linkers, and functional groups, but at present we do not have a formalism to quantify optimal coverage of chemical design space. In this work, we develop a machine learning method to quantify similarities of MOFs to analyse their chemical diversity. This diversity analysis identifies biases in the databases, and we show that such bias can lead to incorrect conclusions. The developed formalism in this study provides a simple and practical guideline to see whether new structures will have the potential for new insights, or constitute a relatively small variation of existing structures., At present there are databases with over 500,000 predicted or synthesized MOF structures, yet a method to establish whether a new material adds new information does not exist. Here the authors propose a machine-learning based approach to quantify the structural and chemical diversity in common MOF databases.

Silicon oxide substrates underwent gas-phase functionalization with various aminosilanes, and the resulting surfaces were evaluated for their suitability as a solid support for solid phase peptide synthesis (SPPS). APTES (3-aminopropyltriethoxysilane), APDEMS (3-aminopropyldiethoxymethylsilane), and APDIPES (3-aminopropyldiisopropylethoxysilane) were individually applied to thermal oxide-terminated silicon substrates via gas-phase deposition. Coated surfaces were characterized by spectroscopic ellipsometry (SE), contact angle goniometry, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and spectrophotometry. Model oligopeptides with 16 residues were synthesized on the amino surfaces, and the chemical stabilities of the resulting surfaces were evaluated against a stringent side chain deprotection (SCD) step, which contained trifluoroacetic acid (TFA) and trifluoromethanesulfonic acid (TFMSA). Functionalized surface thickness loss during SCD was most acute for APDIPES and the observed relative stability order was APTESAPDEMSAPDIPES. Amino surfaces were evaluated for compatibility with stepwise peptide synthesis where complete deprotection and coupling cycles are paramount. Model trimer syntheses indicated that routine capping of unreacted amines with acetic anhydride significantly increased purity as measured by MALDI-MS. An inverse correlation between the amine loading density and peptide purity was observed. In general, peptide purity was highest for the lowest amine density APDIPES surface.

We report the syntheses and structures of five metal–organic frameworks (MOFs) based on transition metals (NiII, CuII, and ZnII), adenine, and di-, tri-, and tetra-carboxylate ligands. Adenine, with multiple N donor sites, was found to coordinate to the metal centers in different binding modes including bidentate (through N7 and N9, or N3 and N9) and tridentate (through N3, N7, and N9). Systematic investigations of the protonation states of adenine in each MOF structure via X-ray photoelectron spectroscopy revealed that adenine can be selectively protonated through N1, N3, or N7. The positions of H atoms connected to the N atoms were found from the electron density maps, and further supported by the study of C–N–C bond angles compared to the literature reports. DFT calculations were performed to geometrically optimize and energetically assess the structures simulated with different protonation modes. The present study highlights the rich coordination chemistry of adenine and provides a method for the determination of its protonation states and the location of protonated N atoms of adenine within MOFs, a task that would be challenging in complicated adenine-based MOF structures., The protonation states and positions of hydrogen atoms in five adenine-based metal−organic frameworks were revealed using geometrical studies based on single-crystal XRD data supported by XPS spectra and DFT calculations.

A novel sequential processing approach to fabricate versatile fibres containing encapsulated materials is presented. It is based on developing highly porous fibres, to be filled with functional materials and coated with protective layers. Applicability of the approach to develop porous poly(methyl methacrylate) (PMMA) fibres with encapsulated antibacterial salts within a coating is demonstrated. The salt was introduced to the fibre via a sacrificial solvent. Desired solvent properties to ensure successful filling was discussed. The salt was encapsulated via spray coating. The coating characteristics were tuned via vapour treatment to facilitate controllable radial salt release. Large volume axial release was also achieved due to the axial pore connectivity. Compared to state-of-the-art methods to produce fibres with functional material inclusions such as emulsion electrospinning, the method presented herein, due to its sequential processing nature, offers greater freedom in material selection and thus broad applications of the fibres.

Background Fat grafting is a common procedure in plastic surgery. A major limitation is unpredictable graft retention, in part caused by inadequate oxygen delivery during the early posttransfer period. Methods The authors present a bioengineered approach to the design of a fat graft based on mathematical theory, which can estimate the limitations of oxygen delivery. To simplify the problem, four variables were defined: (1) recipient-site oxygen partial pressure; (2) adipose tissue oxygen permeability; (3) adipose tissue oxygen consumption rate; and (4) fat graft size. Recipient-site oxygen partial pressure and adipose tissue oxygen permeability were estimated from literature, whereas adipose tissue oxygen consumption rate was measured using stirred microchamber technology. Calculations were performed in both spherical and planar geometry to calculate the maximum allowable fat graft size from an oxygen delivery standpoint. Results As expected, planar geometry is less favorable for oxygenation but represents a realistic configuration for a fat graft. Maximum allowable fat graft thickness is only approximately 1 to 2 mm at external oxygen partial pressures of 10 to 40 mm Hg; any thicker and an anoxic or necrotic core likely develops. Given a reasonably large surface area and assuming several planes of injection, the maximum allowable fat graft volume is tens of milliliters. Conclusions A systematic bioengineered approach may help better design a fat graft. Applying principles of mass transfer theory can predict whether a fat graft has a favorable chance of surviving from an oxygen delivery standpoint and can direct the development of strategies for improved fat graft oxygenation.

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Metal-organic frameworks (MOFs) can theoretically yield a nearly infinite number of nanoporous materials, which represents a combinatorial design challenge that demands computational tools rather than experimental trial-and-error. Here we report Quantitative Structure–Property Relationship (QSPR) models to identify high-performing MOFs for methane purification solely using geometrical features. The CO2working capacity and CO2/CH4selectivity of ca. 320,000 hypothetical MOF structures was computed at conditions relevant to natural gas purification using grand canonical Monte-Carlo (GCMC) simulations. Using 32,500 MOF structures we calibrated binary decision tree (DT) and support vector machine (SVM) models that can accurately identify high-performing MOFs based on their pore size, void fraction and surface area. DT models yielded guidelines of pore size, void fraction and surface area for designing high-performing materials. The SVM machine learning classifiers could be used to quickly pre-screen MOFs, such that compute intensive GCMC simulations are not performed on all structures. The SVM classifiers were tested on ca. 290,000 MOFs that were not part of the training set and could correctly identify up to 90 % of high-performing MOFs while only flagging a fraction of the MOFs for more rigorous screening. QSPR models constitute efficient computational tools for the virtual screening of large structural libraries and provide rational design rules for the discovery of sorbents for methane purification.

Bdellovibrio bacteriovorus is a predator of Gram-negative bacteria and there is limited research on its utility for decontamination of post-harvest produce. The objective of this research was to determine reduction of E. coli O157:H7 and Salmonella on lettuce and carrot by B. bacteriovorus 109 (Bb109) and evaluate its survival and E. coli in buffer and on lettuce following gamma radiation exposure. Bb109 was cultured on ML35, filtered, and predator cells were suspended in buffer. Produce and buffer were co-inoculated with E. coli and Salmonella, separately; and Bb109 applied. In a separate experiment, Bb109 were inoculated on lettuce and suspended in buffer, then irradiated at 0.25–1.0 kGy treatments. E. coli and Salmonella in buffer were reduced by Bb109 0.4–3.9 and 0.9–2.6 logs, respectively. The predation of E. coli by Bb109 on carrot and lettuce resulted in 0.3–1.8 log reductions, and for Salmonella on the same produce, they were 0.9 and 1.2 logs, respectively. In radiation sensitivity assays, Bb109 populations in buffer and lettuce were inactivated by 3–5 logs (0.5 kGy). Bdellovibrio could aid the mortality of pathogenic bacteria during post-harvest treatment or in hurdle interventions of post-harvest produce. No previous data on Bdellovibrio exposure to radiation is available.

Charge equilibration (Qeq) methods can estimate the electrostatic potential of molecules and periodic frameworks by assigning point charges to each atom, using only a small fraction of the resources needed to compute density functional (DFT)-derived charges. This makes possible, for example, the computational screening of thousands of microporous structures to assess their performance for the adsorption of polar molecules. Recently, different variants of the original Qeq scheme were proposed to improve the quality of the computed point charges. One focus of this research was to improve the gas adsorption predictions in metal-organic frameworks (MOFs), for which many different structures are available. In this work, we review the evolution of the method from the original Qeq scheme, understanding the role of the different modifications on the final output. We evaluated the result of combining different protocols and set of parameters, by comparing the Qeq charges with high quality DFT-derived DDEC charges for 2338 MOF structures. We focused on the systematic errors that are attributable to specific atom types to quantify the final precision that one can expect from Qeq methods in the context of gas adsorption where the electrostatic potential plays a significant role, namely, CO2 and H2S adsorption. In conclusion, both the type of algorithm and the input parameters have a large impact on the resulting charges, and we draw some guidelines to help the user to choose the proper combination of the two for obtaining a meaningful set of charges. We show that, considering this set of MOFs, the accuracy of the original Qeq scheme is often still comparable with the most recent variants, even if it clearly fails in the presence of certain atom types, such as alkali metals., European Union (EU); H2020; European Research Council (ERC)-2017-Starting Grant; Swedish Science Council (VR); Swiss National Supercomputing Centre (CSCS); European Research Council (ERC) European Union’s Horizon 2020 research and innovation programme; NCCR Marvel; INSPIRE Potentials Master's Fellowship; COSMOS

Many multifunctional composite structures incorporate porosity at various length scales to increase the available surface area of a functional component. One material system of particular interest is activated or porous carbon fibers and nanofibers that can serve as structural reinforcement as well as providing active surface for added functionality. A key question in the design and manufacture of these fibers is to what degree the induced pore affects the mechanical properties by inducing discontinuities in the material. To address this problem, mechanics of porous carbon nanofibers (CNFs) was studied for the first time as a function of their porous structure. Hollow CNF with porous shell was prepared by coaxial electrospinning a polyacrylonitrile/poly(methyl methacrylate) (PMMA) blend shell with a PMMA core. PMMA was removed by thermal decomposition during pyrolysis to form pores. Solid-shell CNF was prepared as a control with no PMMA in the shell. Results show that the modulus and strength of the porous-shell CNF with a porosity of 19.2 ± 1.3% were 65.0 ± 6.2 and 1.28 ± 0.14 GPa respectively, 13.9 ± 2.1% and 35.5 ± 4.9% lower than those of the solid-shell CNF. Finite-element analysis models were developed to decouple the effect of stress concentration and reduced load-bearing area in porous CNFs on their mechanical properties. The model predictions were in general agreement with the experimental results and were used to identify the most critical parameters that can affect load bearing in porous nanofibers. Considering the comparison of the experimental and modeling results, the intrinsic material strength (of the solid parts) does not seem to be affected by inducing pores; thus, fiber and pore geometries might be developed where the load paths are designed for even less of a strength loss.

Metal–organic frameworks (MOFs) have emerged as versatile materials for applications ranging from gas separation and storage, catalysis, and sensing. The attractive feature of MOFs is that, by changing the ligand and/or metal, they can be chemically tuned to perform optimally for a given application. In most, if not all, of these applications one also needs a material that has a sufficient mechanical stability, but our understanding of how changes in the chemical structure influence mechanical stability is limited. In this work, we rationalize how the mechanical properties of MOFs are related to framework bonding topology and ligand structure. We illustrate that the functional groups on the organic ligands can either enhance the mechanical stability through formation of a secondary network of nonbonded interactions or soften the material by destabilizing the bonded network of a MOF. In addition, we show that synergistic effect of the bonding network of the material and the secondary network is required to achieve optimal mechanical stability of a MOF. The developed molecular insights in this work can be used for systematic improvement of the mechanical stability of the materials by careful selection of the functional groups., The mechanical stability of metal−organic frameworks can be significantly enhanced and/or tuned by rational decoration of ligands with functional groups via secondary networks.

Control of foodborne pathogens on post-harvest produce may be improved by combined treatments. Hurdle applications may enhance the lethal effects of non-thermal interventions on pathogenic bacteria. We evaluated the effects of gamma radiation (0.5 kGy), nisin-based sanitizer (100%), and competitive biocontrol microbes (non-pathogenic Pseudomonas fluorescens) on the survival of Listeria monocytogenes on post-harvest tomato and carrot. Produce storage temperatures (5 and 20 °C) and days (0 and 7), with single, two or three treatment combinations of radiation (R), sanitizer (S) and biocontrol (B) were investigated for pathogen survival. Significant differences (P radiation > biocontrol. Inactivation of Listeria on post-harvest produce may be improved by treatment combinations as hurdle applications could enhance the safety of post-harvest carrot and tomato.

We describe a combined ultrasonic instrument for continuous gas flow measurement and simultaneous real-time binary gas mixture analysis. In the instrument, sound bursts are transmitted in opposite directions, which may be aligned with the gas flow path or at an angle to it, the latter configuration being the best adapted to high flow rates. The combined flow measurement and mixture analysis algorithm exploits the phenomenon whereby the sound velocity in a binary gas mixture at known temperature and pressure is a unique function of the molar concentration of the two components. The instrument is central to a possible upgrade to the present ATLAS silicon tracker cooling system in which octafluoropropane (C F ) evaporative cooling fluid would be replaced by a blend containing up to 25% hexafluoroethane (C 2 F 6 ). The instrument has been developed in two geometries following computational fluid dynamics studies of various mechanical layouts. An instrument with 45 crossing angle has been installed for commissioning in the ATLAS silicon tracker cooling system. It can be used in gas flows up to 20 000 l.min -1 and has demonstrated a flow resolution of 2.3% of full scale for linear flow velocities up to 10 m.s in preliminary studies with air. Other instruments are currently used to detect low levels of C 2 F 8 vapor leaking into the N 2 environmental gas surrounding the ATLAS silicon tracker. A long-duration continuous study of more than a year has demonstrated a sensitivity to mixture variation of better than 5.10 -5 .

We describe an ultrasonic instrument for continuous real-time analysis of the fractional mixture of a binary gas system. The instrument is particularly well suited to measurement of leaks of a high molecular weight gas into a system that is nominally composed of a single gas. Sensitivity < 5 × 10−5 is demonstrated to leaks of octaflouropropane (C3F8) coolant into nitrogen during a long duration (18 month) continuous study. The sensitivity of the described measurement system is shown to depend on the difference in molecular masses of the two gases in the mixture. The impact of temperature and pressure variances on the accuracy of the measurement is analysed. Practical considerations for the implementation and deployment of long term, in situ ultrasonic leak detection systems are also described. Although development of the described systems was motivated by the requirements of an evaporative fluorocarbon cooling system, the instrument is applicable to the detection of leaks of many other gases and to processes requiring continuous knowledge of particular binary gas mixture fractions.

The charge equilibration (QEq) method has been parametrized to reproduce the ab-initio-derived electrostatic potential in a large and diverse training set of 543 metal organic frameworks (MOFs) containing the most popular Zn, Cu, and V structural building units (SBUs), 52 different organic carboxylate- and nitrogen-capped SBUs, and the 17 functional groups. The MOF electrostatic-potential-optimized charge scheme, or MEPO-QEq, was validated by evaluating the CO2 uptake and heats of adsorption in the 543 member training set and a nonoverlapping 693 member validation set. Compared with the results obtained from ab-initio-derived charges, the MEPO-QEq charges give Pearson (linear) and Spearman (rank-order) correlation coefficients of >0.97 for these two sets. MEPO-QEq enables near-ab-initio quality nonbonded electrostatic interactions to be evaluated using the fast QEq method for fast and accurate virtual high-throughput screening of gas-adsorption properties in MOFs.

© 2016 American Chemical Society. In this work, MOF bulk properties are evaluated and compared using several force fields on several well-studied MOFs, including IRMOF-1 (MOF-5), IRMOF-10, HKUST-1, and UiO-66. It is found that, surprisingly, UFF and DREIDING provide good values for the bulk modulus and linear thermal expansion coefficients for these materials, excluding those that they are not parametrized for. Force fields developed specifically for MOFs including UFF4MOF, BTW-FF, and the DWES force field are also found to provide accurate values for these materials’ properties. While we find that each force field offers a moderately good picture of these properties, noticeable deviations can be observed when looking at properties sensitive to framework vibrational modes. This observation is more pronounced upon the introduction of framework charges.

© 2017 American Chemical Society. For applications of metal-organic frameworks (MOFs) such as gas storage and separation, flexibility is often seen as a parameter that can tune material performance. In this work we aim to determine the optimal flexibility for the shape selective separation of similarly sized molecules (e.g., Xe/Kr mixtures). To obtain systematic insight into how the flexibility impacts this type of separation, we develop a simple analytical model that predicts a material’s Henry regime adsorption and selectivity as a function of flexibility. We elucidate the complex dependence of selectivity on a framework’s intrinsic flexibility whereby performance is either improved or reduced with increasing flexibility, depending on the material’s pore size characteristics. However, the selectivity of a material with the pore size and chemistry that already maximizes selectivity in the rigid approximation is continuously diminished with increasing flexibility, demonstrating that the globally optimal separation exists within an entirely rigid pore. Molecular simulations show that our simple model predicts performance trends that are observed when screening the adsorption behavior of flexible MOFs. These flexible simulations provide better agreement with experimental adsorption data in a high-performance material that is not captured when modeling this framework as rigid, an approximation typically made in high-throughput screening studies. We conclude that, for shape selective adsorption applications, the globally optimal material will have the optimal pore size/chemistry and minimal intrinsic flexibility even though other nonoptimal materials’ selectivity can actually be improved by flexibility. Equally important, we find that flexible simulations can be critical for correctly modeling adsorption in these types of systems.

Understanding how crystalline materials are assembled is important for the rational design of metal–organic frameworks (MOFs), through streamlining their synthesis and controlling their properties for targeted applications. Herein, we report for the first time the construction of two 3-dimensional Tb(III) based MOFs; a metastable MOF acting as an intermediate phase, that partially dissolves and transforms into a chemically and thermodynamically stable MOF. This chemical transformation occurs solely in a N,N-dimethylformamide/water solvent mixture, and is triggered when additional energy is provided to the reaction. In situ studies reveal the partial dissolution of the metastable phase after which the MOF components are reassembled into the thermodynamically stable phase. The marked difference in thermal and chemical stability between the kinetically and thermodynamically controlled phases is contrasted by their identical chemical building unit composition.

© 2017 American Chemical Society. Pore volume is one of the main properties for the characterization of microporous crystals. It is experimentally measurable, and it can also be obtained from the refined unit cell by a number of computational techniques. In this work, we assess the accuracy and the discrepancies between the different computational methods which are commonly used for this purpose, i.e, geometric, helium, and probe center pore volumes, by studying a database of more than 5000 frameworks. We developed a new technique to fully characterize the internal void of a microporous material and to compute the probe-accessible and -occupiable pore volume. We show that, unlike the other definitions of pore volume, the occupiable pore volume can be directly related to the experimentally measured pore volumes from nitrogen isotherms.

Designing Carbon Dioxide Traps One widely discussed means of stemming the rise in atmospheric carbon dioxide concentration is to capture the gas prior to its emission and then bury it. The materials currently known to best adsorb CO 2 for this purpose tend to involve amine groups; however, the precise molecular details of adsorption often remain murky, and rational improvement of sorbent properties by structural modification has been challenging. Vaidhyanathan et al. (p. 650 ; see the Perspective by Lastoskie ) have crystallographically resolved the binding motifs of CO 2 in an amine-bearing metal-organic framework solid. Accompanying theoretical simulations matched the experimental observations.

The CETP inhibitor, torcetrapib, was prematurely terminated from phase 3 clinical trials due to an increase in cardiovascular and noncardiovascular mortality. Because nearly half of the latter deaths involved patients with infection, we have tested torcetrapib and other CETPIs to see if they interfere with lipopolysaccharide binding protein (LBP) or bactericidal/permeability increasing protein (BPI). No effect of these potent CETPIs on LPS binding to either protein was detected. Purified CETP itself bound weakly to LPS with a Kdor= 25 microM compared with 0.8 and 0.5 nM for LBP and BPI, respectively, and this binding was not blocked by torcetrapib. In whole blood, LPS induced tumor necrosis factor-alpha normally in the presence of torcetrapib. Furthermore, LPS had no effect on CETP activity. We conclude that the sepsis-related mortality of the ILLUMINATE trial was unlikely due to a direct effect of torcetrapib on LBP or BPI function, nor to inhibition of an interaction of CETP with LPS. Instead, we speculate that the negative outcome seen for patients with infections might be related to the changes in plasma lipoprotein composition and metabolism, or alternatively to the known off-target effects of torcetrapib, such as aldosterone elevation, which may have aggravated the effects of sepsis.

Novel fluorescent derivatives of serotonin have been synthesized and used as tracers for the development of a 5-HT2C fluorescence polarization assay. Serotonin analogs that feature a fluorescent probe attached through an ether linkage at the tryptamine 5-position have high affinity for the 5-HT2C receptor, and affinity is dependent on both linker length and pendent dye. These variables have been optimized to generate Cy3B derivative 5a, which has 10-fold higher 5-HT2C affinity relative to serotonin (Kd=0.23 nM). In receptor activation experiments, 5a acts as a full agonist of 5-HT2C. Upon binding to 5-HT2C cell membranes, 5a shows a robust increase in fluorescence polarization (FP) signal. In an FP binding assay using 5a as a tracer ligand, Ki values for known 5-HT2C agonists and antagonists showed excellent agreement with Ki values from radioligand binding (r2=0.93). The FP ligand assay is suitable for high-throughput drug screening applications with respect to speed of analysis, displaceable signal, precision, and sensitivity to various reagents. A 384-well-based high-throughput assay that is rapid, economical, and predictive of test compounds' ability to bind to the 5-HT2C receptor has been compiled and validated.

Cholesteryl ester transfer protein (CETP) transfers neutral lipids between different types of plasma lipoprotein. Inhibitors of CETP elevate the fraction of plasma cholesterol associated with high-density lipoproteins and are being developed as new agents for the prevention and treatment of cardiovascular disease. The molecular basis of their function is not yet fully understood. To aid in the study of inhibitor interactions with CETP, a torcetrapib-related compound was coupled to different biotin-terminated spacer groups, and the binding of CETP to the streptavidin-bound conjugates was monitored on agarose beads and in a surface plasmon resonance biosensor. CETP binding was poor with a 2.0 nm spacer arm, but efficient with polyethyleneglycol spacers of 3.5 or 4.6 nm. The conjugate based on a 4.6 nm spacer was used for further biosensor experiments. Soluble inhibitor blocked the binding of CETP to the immobilized drug, as did preincubation with a disulfide-containing covalent inhibitor. To provide a first estimate of the binding site for torcetrapib-like inhibitors, CETP was modified with a disulfide-containing agent that modifies Cys-13 of CETP. Mass spectrometry of the modified protein indicated that a single half-molecule of the disulfide was covalently bound to CETP, and peptide mapping after digestion with pepsin confirmed previous reports based on mutagenesis that Cys-13 was the site of modification. Modified CETP was unable to bind to the biosensor-mounted torcetrapib analog, indicating that the binding site on CETP for torcetrapib is in the lipid-binding pocket near the N-terminus of the protein. The crystal structure of CETP shows that the sulfhydryl group of Cys-13 resides at the bottom of this pocket.

Novel fluorescent derivatives of dofetilide (1) have been synthesized. Analogues that feature a fluorescent probe attached through an aliphatic spacer to the central tertiary nitrogen of 1 have high affinity for the hERG channel, and affinity is dependent on both linker length and pendent dye. These variables have been optimized to generate Cy3B derivative 10e, which has hERG channel affinity equivalent to that of dofetilide. When bound to cell membranes expressing the hERG channel, 10e shows a robust increase in fluorescence polarization (FP) signal. In a FP binding assay using 10e as tracer ligand, Ki values for several known hERG channel blockers were measured and excellent agreement with the literature Ki values was observed over an affinity range of 2 nM to 3 muM. 10e blocks hERG channel current in electrophysiological patch clamp experiments, and computational docking experiments predict that the dofetilide core of 10e binds hERG channel in a conformation similar to that previously predicted for 1. These analogues enable high-throughput hERG channel binding assays that are rapid, economical, and predictive of test compounds' potential for prolonged QT liabilities.

A model of mechanical behavior of microcantilever due to mismatch strain during deposition of MEMS structures is analytically derived and experimentally verified. First, a microcantilever, modeled as an Euler-Bernoulli beam, is subjected to deposition of another material and a linear ordinary differential equation which considers the throughthickness variation of the mismatch strain is derived. Second, the deposition analysis is experimentally verified by electroplating of nickel onto an AFM cantilever beam. The deflection of the AFM cantilever is measured in-situ as a function of the deposited thin film thickness through the optical method of Atomic Force Microscopy and the mismatch strain with the through-thickness variation is determined from the experiment results. The usefulness of these equations is that they are indicative of the real time behavior of the structures, i.e. it predicts the deflection of the beam continuously during deposition process.

A finite element implementation of the transient nonlinear Nernst-Planck-Poisson (NPP) and Nernst-Planck-Poisson-modified Stern (NPPMS) models is presented. The NPPMS model uses multipoint constraints to account for finite ion size, resulting in realistic ion concentrations even at high surface potential. The Poisson-Boltzmann equation is used to provide a limited check of the transient models for low surface potential and dilute bulk solutions. The effects of the surface potential and bulk molarity on the electric potential and ion concentrations as functions of space and time are studied. The ability of the models to predict realistic energy storage capacity is investigated. The predicted energy is much more sensitive to surface potential than to bulk solution molarity.

This paper addresses a relatively simple method of measuring Young's modulus of electroplated nickel using an atomic force microscope. The thin layer of nickel to be measured is electroplated onto the tip side of an AFM silicon cantilever, whose Young's modulus and geometric dimensions are well defined from the manufacturer. The resonant frequency and quality factor of the electroplated AFM cantilever are measured by the tapping mode of the AFM and its spring constant is calculated using Sader's method. The spring constant of the electroplated cantilever is also calculated by using the laminar composite beam theory. Comparing two spring constants, Young's modulus of electroplated nickel is determined. The measured Young's modulus of nickel at the end of each plating step ranged between 148.04 GPa and 159.90 GPa with a relative uncertainty of 4.21%.

This study describes the use of cyclic peptides for use in the selection of single-chain (ScFv) antibodies specific for the HIV-1 coreceptor CCR5, a representative G-protein-coupled receptor (GPCR). A tandem ligation strategy was developed for preparing biotinylated cyclic peptides, first through an orthogonal end-to-end ligation and then a chemoselective ligation with functionalized biotin. Cyclic peptides mimicking the extracellular loops of CCR5 and their unconstrained counterparts were then used for solution-phase selection of ScFv antibodies from a phage display antibody library. Antibodies reactive with CCR5 on cells were detected using a homogeneous high throughput assay. Of 19 isolated ScFv antibodies that bound to CCR5+ cells, three inhibited CCR5-mediated but not CXCR4-mediated HIV infection. Only ScFvs selected by binding to cyclic constrained peptides exhibited inhibitory activity. Our results demonstrate that surface-antigen mimetics of a GPCR are effective tools for selecting active, site-specific ScFv antibodies that hold promise as immunological reagents and therapeutics.

An in vitro reactive intermediate screening assay, incorporating the use of the close analog of glutathione, glutathione ethyl ester (GSH-EE) as a conjugating agent, was developed to identify compounds that form reactive intermediates in an in vitro metabolite generating system. The biological assay consisted of substrate [s] = 10 microM, human liver microsomes, an NADPH generating system and glutathione ethyl ester. Conjugates were extracted from the biological matrix using a combination of protein precipitation and a semi-automated 96-well plate solid phase extraction (SPE) procedure. A micro-bore liquid chromatography-micro-electrospray ionization-tandem mass spectrometry (microLC-microESI-MS/MS) method detected glutathione ethyl ester conjugates using selected reaction monitoring (SRM) to simultaneously monitor for multiple MH+ to [MH - 129]+ transitions, where the 129 mass unit (Da) represents the neutral loss of the pyroglutamate moiety from GSH-EE. The multiple MH+ to [MH - 129]+ transitions (SRM mass table) were generated for potential reactive intermediates of each compound. Glutathione (GSH) and GSH-EE conjugate standards were used to evaluate MS detection sensitivity. Based on direct comparison of standard curve data, an approximate 10-fold increase in sensitivity was observed for conjugates containing GSH-EE moiety versus GSH. In vitro experiments were conducted using literature substrates acetaminophen, rosiglitazone, clozapine, diclofenac and either GSH-EE or GSH as a reactive intermediate conjugating agent. An increase in detection sensitivity was observed for each GSH-EE conjugate and in the case of acetaminophen-GSH-EE the peak area increase was approximately 80-fold. Twelve drug compounds, each having known biotransformation mechanisms, were used to further test the detection capabilities of the assay and establish a concordance to literature data. When GSH was used in the assay, conjugates were detected for 4 out of the 12 test compounds (33%). When GSH-EE was used in the assay, conjugates were detected for 10 out of the 12 test compounds (83%).

The effects of pH (4.0–5.5), acid identity (acetic, citric, lactic, malic, and hydrochloric), and the induction of pH-dependent stationary phase acid resistance on the radiation resistance of E. coli O157:H7 Ent-C9490 was studied using cells grown in Tryptic Soy Broth with and without dextrose (induced and non-induced to acid resistance) and then resuspended in brain–heart infusion broth containing 5 g/l of an organic acid and acidified with concentrated hydrochloric acid. After treatment with gamma radiation, the number of survivors was determined by plating on brain–heart infusion agar (injured and non-injured cells) and MacConkey agar (non-injured cells), and the data used to calculate radiation D -values. The induction of pH-dependent stationary phase acid resistance consistently provided the enterohemorrhagic E. coli strain cross-protection from subsequent irradiation, increasing radiation D -values by 1.2–3.3-fold, depending on the organic acid present. The radiation resistance of E. coli varied with acid identity, but was largely unaffected by pH within the range examined. The results indicate that induction of cross-protection resulting from induction of acid resistance is a factor that should be considered to accurately determine the radiation dose needed to inactivate enterohemorrhagic E. coli in foods.

The CLEO-III silicon vertex detector is a 4-layer device with double-sided silicon sensors arranged in a barrel design, covering 93% of the solid angle. After initially meeting its design goals of signal-to-noise performance and spatial resolution, the signal efficiency deteriorated on the rφ sensor side in the two innermost layers due to radiation induced sensor effects. Operation of the two outermost layers and the z -coordinate readout in all layers is stable.

The design and operation of the CLEO III silicon vertex detector is described in this report. This detector consists of four layers of double-sided silicon wafers covering 93% of the solid angle. After initially meeting its signal-to-noise and spatial resolution design goals, the r − φ side efficiency of layers 1 and 2 decreased dramatically due to radiation-induced sensor effects.

We investigate and address the performance limitations of the ATLAS silicon tracker fluorocarbon evaporative cooling system operation in the cooling circuits of the barrel silicon microstrip (SCT) sub-detector. In these circuits the minimum achievable evaporation temperatures with C(3)F(8) were higher than the original specification, and were thought to allow an insufficient safety margin against thermal runaway in detector modules subject to a radiation dose initially foreseen for 10 years operation at LHC. We have investigated the cooling capabilities of blends of C(3)F(8) with molar admixtures of up to 25% C(2)F(6), since the addition of the more volatile C(2)F(6) component was expected to allow a lower evaporation temperature for the same evaporation pressure.A custom built recirculator allowed the in-situ preparation of C(2)F(6)/C(3)F(8) blends. These were circulated through a representative mechanical and thermal setup reproducing an as-installed ATLAS SCT barrel tracker cooling circuit. Blend molar compositions were verified to a precision of 3.10(−)(3) in a custom ultrasonic instrument.Thermal measurements in a range of C(2)F(6)/C(3)F(8) blends were compared with measurements in pure C(3)F(8). These indicated that a blend with 25% C(2)F(6) would allow a reduction in evaporation temperature of around 9(o)C to below -15(o)C, even at the highest module power dissipations envisioned after 10 years operation at LHC. Such a reduction would allow more than a factor two in safety margin against temperature dependant leakage power induced thermal runaway.Furthermore, a blend containing up to 25% C(2)F(6) could be circulated without changes to the on-detector elements of the existing ATLAS inner detector evaporative cooling system.

Enzymatic digests of proteins S-alkylated with iodoacetamide may contain peptides with N-terminal S-carbamoylmethylcysteine. These can be partly converted to a form with 17 Da lower mass and increased HPLC retention. Proof by synthesis supported by MS/MS and NMR spectroscopy was used to show that N-terminal S-carbamoylmethyl-l-cysteine can cyclize, losing NH3 to form an N-terminal residue of (R)-5-oxoperhydro-1,4-thiazine-3-carboxylic acid. The abbreviation Otc is proposed for the (R)-5-oxoperhydro-1,4-thiazine-3-carbonyl residue. The rate of cyclization is significant in 0.1 M NH4HCO3 at 37 °C, with the half-life of the acyclic form being 10−12 h for several peptides tested. This is similar to the rate at which N-terminal pyroglutamate forms from N-terminal glutamine. Keywords: iodoacetamide • peptide mapping • cyclization • mass spectrometry • S-carbamoylmethylcysteine

CLEO III is the new experimental phase of the CLEO experiment at the CESR accelerator. Both the accelerator and the detector have recently been upgraded. A new charged particle tracking system with the addition of a ring imaging Cherenkov particle identification system has been installed. A major part of the tracking system upgrade was the construction of a new four-layer double-sided silicon tracker with 93% solid angle coverage and new readout electronics. The CLEO III upgrade was completed in February 2000 with the installation of the silicon detector. CLEO III has finished the commissioning phase and is now taking data. The design of the detector and first performance results are presented here.

Two diketopiperazines, cyclo-(L-prolyl-L-glycine) and cyclo-(L-phenylalanyl-4R-hydroxy-L-proline), and 2,4-dibromo-6-chlorophenol were isolated from cultures of the marine bacterium, Pseudoalteromonas luteoviolacea. Cyclo-(L-prolyl-L-glycine) and cyclo-(L-phenylalanyl-4R-hydroxy-L-proline) stimulated antibiotic production in this strain. 2,4-Dibromo-6-chlorophenol showed antibacterial activity against methicillin resistant Staphylococcus aureus (MRSA) and the cystic fibrosis associated pathogen Burkholderia cepacia.

A large-displacement electrochemical actuator was designed, fabricated, and tested. The large displacement is obtained by using a corrugated membrane made by physical vapor deposition of Parylene sandwiched with an intermediate layer of sputtered platinum. The layered structure is approximately 8-/spl mu/m thick, with 26 grooves approximately 120-/spl mu/m deep, and with a radial period of 350 /spl mu/m. The electrochemical cell consists of platinum electrodes with a 1 M H/sub 2/SO/sub 4/ solution. Hydrogen and oxygen gas is generated to displace the membrane. Although the actuator can operate at a voltage as low as 1.23 V, the experimentally determined efficiency of converting electrical energy to mechanical work is only 0.37%. The governing equations for the conservation of mass, momentum (equilibrium), energy, and the entropy generation rate were formulated assuming that the gas bubbles either nucleate without growth or grow without nucleation. For the nucleation case, simulations were performed for constant pressure isothermal actuation, and the average experimental efficiency was bounded by simulations with gas bubble radii between 1/spl times/10/sup -6/ m and 1/spl times/10/sup -6/ m. The predicted ratio of the power dissipated to the electrical power supplied is 1.37 for isothermal actuation.

A wet chip electro-fluidic packaging technology based on electroplating is described. An electroplated gold seal provides the sensor's fluid connection to a silicon multi-chip module. A hermetic seal is obtained using the gold–silicon eutectic bond. The sensor's electrical connections to the multi-chip module are made by eutectic bonding electroplated gold–tin solder bumps on the sensor to gold pads on the substrate. The fluid and electrical connections are made simultaneously, and the process is compatible with the flip-chip bonding technique.

Miniature fluid pumps, measuring 15×4×1 mm, have been microfabricated with silicon, glass, and polyimide. Pumps have been tested with deionized water and 10% glycerol solutions as the working solutions. The pumps have been operated with a pneumatic drive or a piezoelectric drive. Flow rates from 0.1 to 110 μl min−1 have been achieved. The maximum pressure generated by the pumps was 56 cm of water. Pumps have been operated with a dialysis probe and with a microchannel load. The pump lifetime is limited by the degradation in the performance of the polyimide components in the pump. The power consumption was less than 1 mW at a drive frequency of 10 Hz.

Hemofiltrate C-C chemokine (HCC)-1 is a recently cloned C-C chemokine that is structurally similar to macrophage inflammatory protein (MIP)-1alpha. Unlike most chemokines, it is constitutively secreted by tissues and is present at high concentrations in normal human plasma. Also atypical for chemokines, HCC-1 is reported not to be chemotactic for leukocytes. In this paper, we have investigated the chemokine receptor usage and downstream signaling pathways of HCC-1. Cross-desensitization experiments using THP-1 cells suggested that HCC-1 and MIP-1alpha activated the same receptor. Experiments using a panel of cloned chemokine receptors revealed that HCC-1 specifically activated C-C chemokine receptor (CCR)1, but not closely related receptors, including CCR5. HCC-1 competed with MIP-1alpha for binding to CCR1-transfected cells, but with a markedly reduced affinity (IC50 = 93 nM versus 1.3 nM for MIP-1alpha). Similarly, HCC-1 was less potent than MIP-1alpha in inducing inhibition of adenylyl cyclase in CCR1-transfected cells. HCC-1 induced chemotaxis of freshly isolated human monocytes, THP-1 cells, and CCR1-transfected cells, and the optimal concentration for cell migration (100 nM) was approximately 100-fold lower than that of MIP-1alpha (1 nM). These data demonstrate that HCC-1 is a chemoattractant and identify CCR1 as a functional HCC-1 receptor on human monocytes.

A cubic metal-organic framework with an unprecedented octanuclear secondary building unit (SBU) was isolated. The obtained SBU is composed of 8 Co(II) ions at each vertex, 6 μ4-OH groups at each face, and 12 cpt(-) ligands framing the metal core. The cuboctahedra arrange in a ubt framework topology, eliciting a highly symmetrical MOF structure. Magnetic measurements as well as DFT calculations on this crystalline MOF reveal intramolecular antiferromagnetic coupling between Co(II) ions in the octanuclear SBU.

We describe a combined ultrasonic instrument for continuous gas flow measurement and simultaneous real-time binary gas mixture analysis. In the instrument, sound bursts are transmitted in opposite directions, which may be aligned with the gas flow path or at an angle to it, the latter configuration being the best adapted to high flow rates. Custom electronics based on Microchip® dsPIC and ADuC847 microcontrollers transmits 50kHz ultrasound pulses and measures transit times in the two directions together with the process gas temperature and pressure. The combined flow measurement and mixture analysis algorithm exploits the phenomenon whereby the sound velocity in a binary gas mixture at known temperature and pressure is a unique function of the molar concentration of the two components. The instrument is central to a possible upgrade to the present ATLAS silicon tracker cooling system in which octafluoropropane (C3F8) evaporative cooling fluid would be replaced by a blend containing up to 25% hexafluoroethane (C2F6). Such a blend will allow a lower evaporation temperature and will afford the tracker silicon substrates a better safety margin against leakage current-induced thermal runaway caused by cumulative radiation damage as the luminosity profile at the CERN Large Hadron Collider (LHC) increases. The instrument has been developed in two geometries following computational fluid dynamics studies of various mechanical layouts. An instrument with 45° crossing angle has been built in stainless steel and installed for commissioning in the ATLAS silicon tracker evaporative fluorocarbon cooling system. It can be used in gas flows up to 20000 l.min-1, and has demonstrated a flow resolution of 2.3% of full scale for linear flow velocities up to 10 m.s-1 in preliminary studies with air. Other instruments are currently used to detect low levels of C3F8 vapour leaking into the N2 environmental gas surrounding the ATLAS silicon tracker. Gas from several parts of the tracker is aspirated through two instruments and analyzed. A long duration continuous study of more than a year has demonstrated a sensitivity to mixture variation of better than 5.10-5. The developed instrument has many applications where continuous knowledge of binary gas composition is required. Such applications include anaesthesia, the analysis of hydrocarbon mixtures, and vapour mixtures for semiconductor manufacture.

Analysis of NOE cross-peaks in 1H NMR ROESY spectra of Ac-Hel1-Ala6-OH in water and in water−trifluoroethanol mixtures demonstrates that the template Ac-Hel1 initiates an α-helix in a linked hexa-Ala peptide. Other NMR parameters and circular dichroism spectra are consistent with the presence of an α-helix, frayed at the C-terminus. Effects of NaCl, urea, temperature, and trifluoroethanol on the stability of a short alanine helix are reported.

The architecture of the pore-region of a voltage-gated K+ channel, Kv1.3, was probed using four high affinity scorpion toxins as molecular calipers. We established the structural relatedness of these toxins by solving the structures of kaliotoxin and margatoxin and comparing them with the published structure of charybdotoxin; a homology model of noxiustoxin was then developed. Complementary mutagenesis of Kv1.3 and these toxins, combined with electrostatic compliance and thermodynamic mutant cycle analyses, allowed us to identify multiple toxin-channel interactions. Our analyses reveal the existence of a shallow vestibule at the external entrance to the pore. This vestibule is approximately 28-32 A wide at its outer margin, approximately 28-34 A wide at its base, and approximately 4-8 A deep. The pore is 9-14 A wide at its external entrance and tapers to a width of 4-5 A at a depth of approximately 5-7 A from the vestibule. This structural information should directly aid in developing topological models of the pores of related ion channels and facilitate therapeutic drug design.

Longissimus dorsi from beef was inoculated with Listeria monocytogenes and the effect of gamma irradiation on the survival of this pathogen at -60 to +15 o C was determined. Radiation D-values were determined for inactivation of L. monocytogenes at 5 o C intervals from -20 to 5 o C. These data were used to develop an equation to predict the response to gamma radiation within that range. An abrupt increase in resistance occurred at -5 o C. The radiation D-value was 0.45 kGy at 0 o C, 0.77 kGy at -5 o C and 1.21 kGy at -20 o C. A straight line was obtained when the log 10 of the D-values from -5 to -20 o C was plotted vs the reciprocal of the absolute temperature. This led us to calculate a value analogous to the Arrhenius activation energy for inactivation of L. monocytogenes by gamma radiation

Alkylamines, such as monoethanolamine, are used to scrub CO2 molecules from flue gas streams, however, as they form strong chemical bonds (85–105 kJmol ), the post-capture recovery of the amine is energy-intensive (130–150 8C including heating the entire aqueous solution). Alternatively, the use of less-basic amines, such as aryl amines, could favor strong physisorption (30–50 kJmol ) with CO2, rather than chemisorption. This would mean a porous compound with such amine groups could give easy-on/easy-off reversible CO2 capture balanced with selectivity. To obtain high efficiency at lower partial pressures, the material, along with having strong CO2 binding sites, needs to have reasonable surface area for capacity. Metal–organic frameworks (MOFs) are widely studied for gas sorption owing to the ability to modify pore sizes, shapes, and surfaces. Functionalizing with specific interaction sites is being actively studied as a route to selective gas capture. Computational modeling can give tremendous insight to the sorption properties of a MOF. We recently reported a zinc aminotriazolato oxalate MOF, {Zn2(Atz)2(ox)} (2), exhibiting amine-lined pores and a high heat of adsorption for CO2 (ca. 40 kJmol ). Further studies showed that the CO2 binding sites could be located crystallographically. These data offered an exceptional opportunity to validate a suite of computational methods to model not only the CO2 isotherm, but also the locations of binding sites and role of specific interactions to the overall CO2 binding enthalpy. The present study applies these methods to understanding CO2 uptake in another MOF, {Zn3(Atz)3(PO4)} (1), that intuitively should give better CO2 capture properties. In comparison to {Zn2(Atz)2(ox)}, only two-thirds of the number of trianionic phosphate groups are required to charge compensate [Zn(Atz)] layers, so larger, amine-lined pores were anticipated and observed. Despite this, the CO2 uptake (at 273 K) and heat of adsorption do not exceed those of 2. The computational methods provide crucial insight to understanding these phenomena and demonstrate the wide spread applicability of such techniques to ascertain binding details in MOFs not directly accessible by experiment. Although the role of the amine functionalities in 1 is surprisingly diminished, the cooperative interactions between CO2 molecules are found to augment overall binding by over 7 kJmol , a significant result for CO2 capture in any porous material. Solvothermal reaction of basic ZnCO3 with 3-amino-1,2,4triazole, H3PO4, and NH4OH gave {Zn3Atz3(PO4)(H2O)3.5}, 1·(H2O)3.5, in both single-crystal and bulk phases (Supporting Information, Figure S1). The aminotriazole ligand has been employed to construct otherMOFs, including with Zn ions, but has not been extensively studied for CO2 capture excepting 2. 1·(H2O)3.5 is made up of cationic Zn–Atz layers pillared by PO4 anions to form a 3D porous network (Figure 1). The Zn(Atz) layers lie in the ac plane and contain three independent Zn ions and Atz ligands. No amine groups coordinate to Zn ions; ligation is exclusively through triazole nitrogen atoms. Pillaring of these layers by the phosphate ions results in a 3D network of pores (accounting for van der

An elastic beam suspended horizontally over a substrate in liquid electrolyte was subjected to electric, osmotic, and van der Waals forces. The problem, which is governed by four non-dimensional parameters, was solved using the finite element method. The sum of the electric and osmotic forces, the electrochemical force, is usually attractive. However, the electrochemical force can be repulsive for a narrow range of the ion concentration, the initial separation and surface potentials. Furthermore, the beam deflection is not a monotonic function of the applied surface potentials, the bulk ion concentration, or the initial separation between the beam and the substrate. As these parameters are increased monotonically, the beam bends up and then down. The pull-in voltage increases as the bulk ion concentration increases. The pull-in voltage of a double-wall carbon nanotube suspended over a graphite substrate in liquid can be less than or greater than the pull-in voltage in air, depending on the bulk ion concentration. The critical separation between the DWCNT and the substrate increases with the bulk ion concentration. However, for a given bulk ion concentration, the critical separation is independent of the electric potentials. Furthermore, the critical separation is approximately equal in liquid and air.