Biomimetic Nanostructured Surfaces with Designer Mechanics and Geometry for Broad Applications

A powerful fabrication platform for a wide range of biomimetic, high-aspect-ratio nanostructured surfaces is introduced. The principles of soft lithography are extended into a double-mold replication process, whereby a master topography is mapped onto an elastomeric inverse mold and replicated in arbitrary multiple material and stiffness gradients, and an array of modified geometries. Control of geometry via deformation of the inverse mold and control of stiffness via prepolymer mixing are discussed. New capabilities enabled by our approach include biomimetic actuation/sensor arrays with programmable biases, precisely tunable mechanical and geometric properties for optical or wetting applications, and flexible curved substrates. Indeed, flexibly anchored ciliary high-aspect-ratio nanostructures are now possible, and a proof-of-principle is described.Engineering and Applied Science

Bioinspired, Dynamic, Structured Surfaces for Biofilm Prevention

Bacteria primarily exist in robust, surface-associated communities known as biofilms, ubiquitous in both natural and anthropogenic environments. Mature biofilms resist a wide range of biocidal treatments and pose persistent pathogenic threats. Treatment of adherent biofilm is difficult, costly, and, in medical systems such as catheters, frequently impossible. Adding to the challenge, we have discovered that biofilm can be both impenetrable to vapors and extremely nonwetting, repelling even low surface tension commercial antimicrobials. Our study shows multiple contributing factors, including biochemical components and multiscale reentrant topography. Reliant on surface chemistry, conventional strategies for preventing biofilm only transiently affect attachment and/or are environmentally toxic. In this work, we look to Nature’s antifouling solutions, such as the dynamic spiny skin of the echinoderm, and we develop a versatile surface nanofabrication platform. Our benchtop approach unites soft lithography, electrodeposition, mold deformation, and material selection to enable many degrees of freedom—material, geometric, mechanical, dynamic—that can be programmed starting from a single master structure. The mechanical properties of the bio-inspired nanostructures, verified by AFM, are precisely and rationally tunable. We examine how synthetic dynamic nanostructured surfaces control the attachment of pathogenic biofilms. The parameters governing long-range patterning of bacteria on high-aspect-ratio (HAR) nanoarrays are combinatorially elucidated, and we discover that sufficiently low effective stiffness of these HAR arrays mechanoselectively inhibits ~40% of Pseudomonas aeruginosa biofilm attachment. Inspired by the active echinoderm skin, we design and fabricate externally actuated dynamic elastomer surfaces with active surface microtopography. We extract from a large parameter space the critical topographic length scales and actuation time scales for achieving nearly ~80% attachment reduction. We furthermore investigate an atomically mobile, slippery liquid infused porous surface (SLIPS) inspired by the pitcher plant. We show up to 99.6% reduction of multiple pathogenic biofilms over a 7-day period under both static and physiologically realistic flow conditions—a ~35x improvement over state-of-the-art surface chemistry, and over a far longer timeframe. Moreover, SLIPS is shown to be nontoxic: bacteria simply cannot attach to the smooth liquid interface. These bio-inspired strategies significantly advance biofilm attachment prevention and promise a tremendous range of industrial, clinical, and consumer applications.Engineering and Applied Science

Water immersion increases the concentration of the immunoreactive N-terminal fragment of pro-atrial natriuretic factor in human plasma

Atrial natriuretic factor (ANF) N-terminal (ANF 1–98) and C-terminal (ANF 99–126) fragments were determined by radioimmunoassay in human plasma. Mean basal plasma ANF N-terminal concentrations in 9 healthy subjects were 461 ± 58 fmol/ml,significantly (p<0.0001) higher than ANF C-terminal concentrations ( 4.8 ± 0.5 fmol/ml). Central volume stimulation by one hour head-out water immersion (WI) induced a significant (p<0.01) increase of the C-terminal peptide levels to 11.6 ± 2.3 fmol/ml,paralleled by a significant (p<0.001) increase of the N-terminal fragment levels to 749 ± 96 fmol/ml. Increases of plasma concentrations of both fragments upon WI correlated significantly (r=0.71;p<0.05). These data suggest cosecretion of the N-terminal fragment with the C-terminal fragment of pro ANF 1–126 following a physiological stimulus of ANF release in man

Biomimetic, Hierarchical, Multidimensional Patterning of Conductive Polymers on High-Aspect-Ratio Microstructures

Engineering and Applied Science

Discrete conformal maps and ideal hyperbolic polyhedra

We establish a connection between two previously unrelated topics: a particular discrete version of conformal geometry for triangulated surfaces, and the geometry of ideal polyhedra in hyperbolic three-space. Two triangulated surfaces are considered discretely conformally equivalent if the edge lengths are related by scale factors associated with the vertices. This simple definition leads to a surprisingly rich theory featuring M\"obius invariance, the definition of discrete conformal maps as circumcircle preserving piecewise projective maps, and two variational principles. We show how literally the same theory can be reinterpreted to addresses the problem of constructing an ideal hyperbolic polyhedron with prescribed intrinsic metric. This synthesis enables us to derive a companion theory of discrete conformal maps for hyperbolic triangulations. It also shows how the definitions of discrete conformality considered here are closely related to the established definition of discrete conformality in terms of circle packings.Comment: 62 pages, 22 figures. v2: typos corrected, references added and updated, minor changes in exposition. v3, final version: typos corrected, improved exposition, some material moved to appendice

The Epstein-Glaser approach to pQFT: graphs and Hopf algebras

The paper aims at investigating perturbative quantum field theory (pQFT) in the approach of Epstein and Glaser (EG) and, in particular, its formulation in the language of graphs and Hopf algebras (HAs). Various HAs are encountered, each one associated with a special combination of physical concepts such as normalization, localization, pseudo-unitarity, causality and an associated regularization, and renormalization. The algebraic structures, representing the perturbative expansion of the S-matrix, are imposed on the operator-valued distributions which are equipped with appropriate graph indices. Translation invariance ensures the algebras to be analytically well-defined and graded total symmetry allows to formulate bialgebras. The algebraic results are given embedded in the physical framework, which covers the two recent EG versions by Fredenhagen and Scharf that differ with respect to the concrete recursive implementation of causality. Besides, the ultraviolet divergences occuring in Feynman's representation are mathematically reasoned. As a final result, the change of the renormalization scheme in the EG framework is modeled via a HA which can be seen as the EG-analog of Kreimer's HA.Comment: 52 pages, 5 figure

Automatic structures, rational growth and geometrically finite hyperbolic groups

We show that the set $SA(G)$ of equivalence classes of synchronously automatic structures on a geometrically finite hyperbolic group $G$ is dense in the product of the sets $SA(P)$ over all maximal parabolic subgroups $P$. The set $BSA(G)$ of equivalence classes of biautomatic structures on $G$ is isomorphic to the product of the sets $BSA(P)$ over the cusps (conjugacy classes of maximal parabolic subgroups) of $G$. Each maximal parabolic $P$ is a virtually abelian group, so $SA(P)$ and $BSA(P)$ were computed in ``Equivalent automatic structures and their boundaries'' by M.Shapiro and W.Neumann, Intern. J. of Alg. Comp. 2 (1992) We show that any geometrically finite hyperbolic group has a generating set for which the full language of geodesics for $G$ is regular. Moreover, the growth function of $G$ with respect to this generating set is rational. We also determine which automatic structures on such a group are equivalent to geodesic ones. Not all are, though all biautomatic structures are.Comment: Plain Tex, 26 pages, no figure

Sociodemographic factors and patient perceptions are associated with attitudes to kidney transplantation among haemodialysis patients

Background. Treatment decisions made by patients with chronic kidney disease are crucial in the renal transplantation process. These decisions are influenced, amongst other factors, by attitudes towards different treatment options, which are modulated by knowledge and perceptions about the disease and its treatment and many other subjective factors. Here we study the attitude of dialysis patients to renal transplantation and the association of sociodemographic characteristics, patient perceptions and experiences with this attitude. Methods. In a cross-sectional study, all patients from eight dialysis units in Budapest, Hungary, who were on haemodialysis for at least 3 months were approached to complete a self-administered questionnaire. Data collected from 459 patients younger than 70 years were analysed in this manuscript. Results. Mean age of the study population was 53 +/- 12 years, 54% were male and the prevalence of diabetes was 22%. Patients with positive attitude to renal transplantation were younger (51 +/- 11 versus 58 +/- 11 years), better educated, more likely to be employed (11% versus 4%) and had prior transplantation (15% versus 7%)(P < 0.05 for all). In a multivariate model, negative patient perceptions about transplantation, negative expectations about health outcomes after transplantation and the presence of fears about the transplant surgery were associated, in addition to incre- asing age, with unwillingness to consider transplantation. Conclusions. Negative attitudes to renal transplantation are associated with potentially modifiable factors. Based on this we suggest that it would be necessary to develop standardized, comprehensible patient information systems and personalized decision support to facilitate modality selection and to enable patients to make fully informed treatment decisions

Ornipressin in the treatment of functional renal failure in decompensated liver cirrhosis

In 11 patients with decompensated cirrhosis and deteriorating renal function, the effect of the vasoconstrictor substance 8-ornithin vasopressin (ornipressin; POR 8; Sandoz, Basel, Switzerland) on renal function, hemodynamic parameters, and humoral mediators was studied. Ornipressin was infused at a dose of 6 IU/h over a period of 4 hours. During ornipressin infusion an improvement of renal function was achieved as indicated by significant increases in inulin clearance (+65%), paraaminohippuric acid clearance (+49%), urine volume (+45%), sodium excretion (+259%), and fractional elimination of sodium (+130%). The hyperdynamic circulation was reversed to a nearly normal circulatory state. The increase in systemic vascular resistance (+60%) coincided with a decrease of a previously elevated renal vascular resistance (-27%) and increase in renal blood flow (+44%). The renal fraction of the cardiac output increased from 2.3% to 4.7% (P less than 0.05). A decline of the elevated plasma levels of noradrenaline (2.08-1.13 ng/mL; P less than 0.01) and renin activity (27.6-14.2 ng.mL-1.h-1; P less than 0.01) was achieved. The plasma concentration of the atrial natriuretic factor increased in most of the patients, but slightly decreased in 3 patients. The decrease of renal vascular resistance and the increase of renal blood flow and of the renal fraction of cardiac output play a key role in the beneficial effect of ornipressin on renal failure. These changes develop by an increase in mean arterial pressure, the reduction of the sympathetic activity, and probably of an extenuation of the splanchnic vasodilation. A significant contribution of atrial natriuretic factor is less likely. The present findings implicate that treatment with ornipressin represents an alternative approach to the management of functional renal failure in advanced liver cirrhosis

Medical treatment of ascites in cirrhosis

Medical treatment of cirrhotic ascites is essentially supportive, dictated by the patient's discomfort, impaired cardiovascular or respiratory function and potential for infection. Treatment of ‘simple’ ascites (moderate fluid accumulation, serum albumin > 3.5 g/dl, serum creatinine < 1.5 mg/dl, no electrolyte disturbance) is implemented sequentially. Only 10% of patients respond to dietary sodium restriction and bed rest; most require pharmacotherapy consisting of spironolactone, which increases the proportion of responding patients to 65% and loop diuretics, which may produce clinical improvement in an additional 20% (85% in all); in the remaining 15% of refractory patients, use of novel adjunctive therapies may be attempted. Patients with tense ascites, impaired renal function and electrolyte disturbances merit special consideration before diuretics are introduced. Spironolactone has long been a standard for the treatment of cirrhotic ascites because it directly antagonizes aldosterone. The loop diuretic most frequently added to spironolactone has been furosemide. However, there is preliminary evidence that torasemide may be more effective in some patients. Other investigational agents that may play a role in treatment of patients resistant to conventional drugs include ornipressin (a vasopressin analogue) and atrial natriuretic factor