Strain Stiffening Hydrogels through Self-Assembly and Covalent Fixation of Semi-Flexible Fibers

Biomimetic, strain-stiffening materials are reported, made through self-assembly and covalent fixation of small building blocks to form fibrous hydrogels that are able to stiffen by an order of magnitude in response to applied stress. The gels consist of semi-flexible rodlike micelles of bisurea bolaamphiphiles with oligo(ethylene oxide) (EO) outer blocks and a polydiacetylene (PDA) backbone. The micelles are fibers, composed of 9–10 ribbons. A gelation method based on Cu-catalyzed azide–alkyne cycloaddition (CuAAC), was developed and shown to lead to strain-stiffening hydrogels with unusual, yet universal, linear and nonlinear stress–strain response. Upon gelation, the X-ray scattering profile is unchanged, suggesting that crosslinks are formed at random positions along the fiber contour without fiber bundling. The work expands current knowledge about the design principles and chemistries needed to achieve fully synthetic, biomimetic soft matter with on-demand, targeted mechanical properties.     

Dendrimer-based macromolecular conjugate for the kidney-directed delivery of a multitargeted sunitinib analogue

The development of a macromolecular conjugate of a multitargeted tyrosine kinase inhibitor is described that can be used for renal‐specific delivery into proximal tubular cells. A novel sunitinib analogue, that is, 17864, is conjugated to a NH₂‐PAMAM‐G3 dendrimer via the platinum (II)‐based Universal Linkage System (ULS?). The activity of 17864 is retained after coordination to the ULS linker alone or when coupled to NH₂‐PAMAM‐G3. 17864‐UlS‐NH₂‐PAMAM‐G3 is non‐toxic to proximal tubular cells in vitro. After intravenous administration to mice, 17864‐UlS‐NH₂‐PAMAM‐G3 rapidly and efficiently accumulates in the kidneys. These results are encouraging for future studies focusing on the development of novel therapeutics for the treatment of renal diseases.

     

Probing BRD Inhibition Substituent Effects in Bulky Analogues of (+)-JQ1

A series of bulky organometallic and organic analogues of the bromodomain (BRD) inhibitor (+)-JQ1 have been prepared. The most potent, N-[(adamantan-1-yl)methyl]-2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetraazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetamide, 2e , showed excellent potency with an K_D=ca. 130 nm vs. BRD4(1) and a ca. 2-fold selectivity over BRD4(2) (K_D=ca. 260 nm ). Its binding to the first bromodomain of BRD4 was determined by a protein cocrystal structure.     

Constructing isospectral non‐isomorphic digraphs from hypergraphs

We explore the “oriented line graph” construction associated with a hypergraph, leading to a construction of pairs of strongly connected directed graphs whose adjacency operators have the same spectra. We give conditions on a hypergraph so that a hypergraph and its dual give rise to isospectral, but non‐isomorphic, directed graphs. The proof of isospectrality comes from an argument centered around hypergraph zeta functions as defined by Storm. To prove non‐isomorphism, we establish a Whitney‐type result by showing that the oriented line graphs are isomorphic if and only if the hypergraphs are. © 2009 Wiley Periodicals, Inc. J Graph Theory 63: 231–242, 2010     

Geometrical modelling of foam structures using implicit functions

Mechanical, thermo-mechanical, and fluid dynamic simulations of open-cell foams require an accurate geometry model. Usually, models are derived from computer- tomography (CT) data which do not allow analysing systematically variation and optimisation of the geometry. On the other hand, entirely computer generated models are mostly assembled of primitive objects like cylinders. This disregards strut thickness variations and node rounding which are observed in real open-cell foams. This paper presents an approach to generate models of ceramic open-cell foams using simple objects with variable thickness generated by implicit functions. This approach can also account for cavities within struts and nodes, which are observed in many real foam structures. The specific rounding at the foam nodes can be modelled by applying the transformation of Blinn. The quality of the generated foam models is verified using CT data of real foams.     

Laser heating of solid matter by light-pressure-driven shocks at ultrarelativistic intensities

The heating of solid targets irradiated by 5 x 10(20) W cm(-2), 0.8 ps, 1.05 microm wavelength laser light is studied by x-ray spectroscopy of the K-shell emission from thin layers of Ni, Mo, and V. A surface layer is heated to approximately 5 keV with an axial temperature gradient of 0.6 microm scale length. Images of Ni Ly(alpha) show the hot region has 100 G bar light pressure compresses the preformed plasma and drives a shock into the solid, heating a thin layer.     

Barium sulfate suspension as a negative oral MRI contrast agent: in vitro and human optimization studies

In vitro proton spectroscopy with line-width measurements and MR imaging were performed on various concentrations of commercially available single contrast (SC), double contrast, oral and rectal barium sulfate suspensions, as well as potassium sulfate, barium chloride, barium hydroxide, and 97% pure barium sulfate suspensions. Approximately 500 ml of 20%, 40%, 60%, and 70% w/w suspensions of SC oral barium sulfate suspensions were administered to four normal volunteers, respectively, and MR images were obtained at both 1.5 T and 0.15 T. Subsequently, 500 ml of 60% w/w suspensions of SC oral barium sulfate suspensions were administered to five normal volunteers and imaged at 1.5 T. All of the inert suspensions produced line-width broadening but the SC oral barium sulfate suspension at 50% and 70% stayed in suspension even after hours of standing undisturbed. As much as 80% of the small bowel and the entire colon were well visualized using the combination of 60% or 70% w/w SC barium sulfate suspensions with SE 550/22 and FISP pulse sequences. The effect was less at 0.15 T and also with the SE 2000/45/90 pulse sequences. We conclude that barium sulfate suspensions are useful as oral MRI contrast agents.     

Paramagnetic oil emulsions as oral magnetic resonance imaging contrast agents

The combination of a paramagnetic agent with an oil emulsion can uniformly enhance the small bowel. We discovered that the entire small bowel becomes homogeneously brighter than its surroundings when imaged with all commonly utilized pulse sequences. We have tried various combinations of ferric ammonium citrate, ferrous sulfate, gadolinium-DPTA and corn oil, olive oil and peanut oil. All paramagnetic oil emulsions tested were uniformly distributed throughout the small bowel, but the enhancement effect is much stronger with the ferric ammonium citrate and gadolinium-DPTA oil emulsions. We have also developed a mixture of Geritol, corn oil, ice cream and milk, which uniformly coats the small bowel wall, has good enhancement effect, tastes good, and is nutritious. With this dietary contrast, retroperitoneal structures including the pancreas can be well delineated. We conclude that the combination of a paramagnetic agent with an oil emulsion can work as a safe and effective magnetic resonance imaging (MRI) oral contrast agent with high patient acceptance.