Solvent-free sonochemical one-pot three-component synthesis of 2H-indazolo[2,1-b]phthalazine-1,6,11-triones and 1H-pyrazolo[1,2-b]phthalazine-5,10-diones

A rapid and efficient one-pot three-component protocol for the synthesis of 2H-indazolo[2,1-b]phthalazine-1,6,11-triones 4 and 1H-pyrazolo[1,2-b]phthalazine-5,10-diones 6 has been developed by domino coupling of phthalhydrazide, 1,3-diketones, and aldehydes under solvent-free conditions at 80 °C as well as under solvent-free ultrasound irradiation at room temperature promoted by (S)-camphorsulfonic acid.     

Structure and binding of the H4 histone tail and the effects of lysine 16 acetylation

The H4 histone tail plays a critical role in chromatin folding and regulation--it mediates strong interactions with the acidic patch of proximal nucleosomes and its acetylation at lysine 16 (K16) leads to partial unfolding of chromatin. The molecular mechanism associated with the H4 tail/acidic patch interactions and its modulation via K16 acetylation remains unknown. Here we employ a combination of molecular dynamics simulations, molecular docking calculations, and free energy computations to investigate the structure of the H4 tail in solution, the binding of the H4 tail with the acidic patch, and the effects of K16 acetylation. The H4 tail exhibits a disordered configuration except in the region Ala15-Lys20, where it exhibits a strong propensity for an α-helical structure. This α-helical region is found to dock very favorably into the acidic patch groove of a nucleosome with a binding free energy of approximately -7 kcal mol(-1). We have identified the specific interactions that stabilize this binding as well as the associated energetics. The acetylation of K16 is found to reduce the α-helix forming propensity of the H4 tail and K16's accessibility for mediating external interactions. More importantly, K16 acetylation destabilizes the binding of the H4 tail at the acidic patch by mitigating specific salt bridges and longer-ranged electrostatic interactions mediated by K16. Our study thus provides new microscopic insights into the compaction of chromatin and its regulation via posttranslational modifications of histone tails, which could be of interest to chromatin biology, cancer, epigenetics, and drug design.     

Accurate dispensing of volatile reagents on demand for chemical reactions in EWOD chips

Digital microfluidic chips provide a new platform for manipulating chemicals for multi-step chemical synthesis or assays at the microscale. The organic solvents and reagents needed for these applications are often volatile, sensitive to contamination, and wetting, i.e. have contact angles of <90° even on the highly hydrophobic surfaces (e.g., Teflon? or Cytop?) typically used on digital microfluidic chips. Furthermore, often the applications dictate that the processes are performed in a gas environment, not allowing the use of a filler liquid (e.g., oil). These properties pose challenges for delivering controlled volumes of liquid to the chip. An automated, simple, accurate and reliable method of delivering reagents from sealed, off-chip reservoirs is presented here. This platform overcomes the issues of evaporative losses of volatile solvents, cross-contamination, and flooding of the chip by combining a syringe pump, a simple on-chip liquid detector and a robust interface design. The impedance-based liquid detection requires only minimal added hardware to provide a feedback signal to ensure accurate volumes of volatile solvents are introduced to the chip, independent of time delays between dispensing operations. On-demand dispensing of multiple droplets of acetonitrile, a frequently used but difficult to handle solvent due to its wetting properties and volatility, was demonstrated and used to synthesize the positron emission tomography (PET) probe [(18)F]FDG reliably.     

A systematic approach to magnetic resonance imaging evaluation of epiphyseal lesions

Magnetic Resonance Imaging (MRI) is the preferred modality of choice to image epiphyseal lesions. It provides excellent soft tissue resolution and extent of disease. A wide spectrum of tumor and tumor like lesions can involve the epiphysis. Early and accurate diagnosis as well as appropriate management of epiphyseal lesions is critical as these conditions may lead to disabling complications such as, limb length discrepancy, angular or joint surface deformities and secondary osteoarthritis. In this article, we discuss the role of conventional sequences, such as T1W, fluid sensitive T2W and intravenous (IV) Gadolinium enhanced sequences as well as the additional value of problem solving MRI sequences such as, chemical shift and diffusion weighted imaging. Based on the imaging findings on various MRI sequences and lesion characteristics, a systematic approach directed to the diagnoses of epiphyseal lesions is presented and discussed. MRI features of clinically and biopsy proven examples of the epiphyseal lesions, such as osteomyelitis, intra-osseous abscess, infiltrative malignancy, metastases, transient osteoporosis, subchondral insufficiency fracture, avascular necrosis, osteochondral fracture, osteochondritis dissecans, eosinophilic granuloma and geode are demonstrated. Using this systematic approach, the reader will be able to better characterize epiphyseal lesions with a potential to positively affect patient management.     

Water Vapor Sorption in Cementitious Materials—Measurement,Modeling and Interpretation

The rate and extent of uptake and release of moisture are critical in controlling the behavior of cementitious materials ranging from fluid transport to hygral deformations. While classically determined using an equilibrium (static) salt solution method (Baroghel-Bouny in Cem Concr Res 37:414–437, 2007), advanced capabilities offered by gravimetric dynamic vapor sorption (DVS) analyzers, are now permitting acquisition of sorption spectra at microgram ( $\upmu \hbox {g}$ ) resolution on the order of a few weeks. This work highlights new multicycle determinations of adsorption/desorption isotherms, acquired using a custom-built DVS analyzer for well-hydrated alite and ordinary portland cement pastes over a range of water-to-solid ratios ( $w/s$ , mass basis). Special focus is paid to describe measurement aspects relevant to acquiring reliable spectra, and their interpretation. Sorption isotherms are used to assess transport properties, and sorption hysteresis and its irreversibility following first drying. Based on an optimization-based criterion, the Young-Nelson model is selected to simulate sorption evolutions, including the effects of hysteresis. Sensitivity analyses carried out using this model are used to understand the role of parameters, including porosity and $w/s$ , on the hysteresis that develops from the first to subsequent sorption cycles.     

Selective Localization and Migration of Multiwalled Carbon Nanotubes in Blends of Polycarbonate and Poly(styrene‐acrylonitrile)

Multiwalled carbon nanotubes (MWNTs) have been introduced into blends of polycarbonate (PC) and poly(styrene‐acrylonitrile) (SAN) by melt mixing in a microcompounder. Co‐continuous blends are prepared by either pre‐compounding low amounts of nanotubes into PC or SAN or by mixing all three components together. Interestingly, in all blends, regardless of the way of introducing the nanotubes, the MWNTs were exclusively located within the PC phase, which resulted in much lower electrical resistivities as compared to PC or SAN composites with the same MWNT content. The migration of MWNTs from the SAN phase into the PC phase during common mixing is explained by interfacial effects.

     

Effect of substrate annealing on the quality of pulsed laser deposited Zn1−xMgxO thin films

The annealing effects of sapphire substrate before deposition on the quality of epitaxial Zn_1−xMg_xO thin films grown by pulsed laser deposition are reported. Our Experimental results indicate that the surface quality of Zn_1−xMg_xO thin films and hexagonal columnar growth is improved on the annealed sapphire substrate at high temperatures due to formation of atomic terraces on the substrate surface. The photoluminescence signals also increases with the increasing annealing temperature of the substrate.     

Mechanical characterization of HIV‐1 with a solid‐state nanopore sensor

Enveloped viruses fuse with cells to transfer their genetic materials and infect the host cell. Fusion requires deformation of both viral and cellular membranes. Since the rigidity of viral membrane is a key factor in their infectivity, studying the rigidity of viral particles is of great significance in understating viral infection. In this paper, a nanopore is used as a single molecule sensor to characterize the deformation of pseudo‐type human immunodeficiency virus type 1 at sub‐micron scale. Non‐infective immature viruses were found to be more rigid than infective mature viruses. In addition, the effects of cholesterol and membrane proteins on the mechanical properties of mature viruses were investigated by chemically modifying the membranes. Furthermore, the deformability of single virus particles was analyzed through a recapturing technique, where the same virus was analyzed twice. The findings demonstrate the ability of nanopore resistive pulse sensing to characterize the deformation of a single virus as opposed to average ensemble measurements.