Dynamic measurement of the force required to move a liquid drop on a solid surface.

We measured the forces required to slide sessile drops over surfaces. The forces were measured by means of a vertical deflectable capillary stuck in the drop. The drop adhesion force instrument (DAFI) allowed the investigation of the dynamic lateral adhesion force of water drops of 0.1 to 2 µL volume at defined velocities. On flat PDMS surfaces, the dynamic lateral adhesion force increases linearly with the diameter of the contact area of the solid-liquid interface and linearly with the sliding velocity. The movement of the drop relative to the surfaces enabled us to resolve the pinning of the three-phase contact line to individual defects. We further investigated a 3D superhydrophobic pillar array. The depinning of the receding part of the rim of the drop occurred almost simultaneously from four to five pillars, giving rise to peaks in the lateral adhesion force.

TP53 mutation profile in chronic lymphocytic leukemia: evidence for a disease specific profile from a comprehensive analysis of 268 mutations.

The TP53 mutation profile in chronic lymphocytic leukemia (CLL) and the correlation of TP53 mutations with allele status or associated molecular genetics are currently unknown. We performed a large mutation analysis of TP53 at four centers and characterized the pattern of TP53 mutations in CLL. We report on 268 mutations in 254 patients with CLL. Missense mutations appeared in 74% of cases compared with deletions and insertions (20%), nonsense (4%) and splice site (2%) mutations. The majority (243 of 268) of mutations were located in the DNA-binding domain. Transitions were found in 131 of 268 mutations, with only 41 occurring at methylated CpG sites (15%), suggesting that transitions at CpGs are uncommon. The codons most frequently mutated were at positions 175, 179, 248 and 273; in addition, we detected a common 2-nt deletion in the codon 209. Most mutations (199 of 259) were accompanied by deletion of the other allele (17p-). Interestingly, trisomy 12 (without 17p-) was only found in one of 60 cases with TP53 mutation (without 17p-) compared with 60 of 16 in the cohort without mutation (P=0.006). The mutational profile was not different in the cohorts with and without previous therapy, suggesting that the mechanism underlying the development of mutations may be similar, independent of treatment.

Viscoelastic rheology of colloid-liquid crystal composites.

Gelation in colloidal suspensions is mostly induced by attractive interparticle potentials. Beside these interactions, the mechanical properties of the gel are influenced by morphological aspects like fractality. In suspensions of liquid crystal (LC) and polymeric colloids, solvent-particle interactions dominate and can be changed when the mesogen undergoes phase transition from isotropic to nematic. In case of poly(methyl methacrylate) colloids and 4-pentyl-4'-cyanobiphenyl (5CB), cooling through the isotropic-nematic phase transition results in a cellular network. Such network formation is accompanied by a strong evolution of the mechanical properties. Shear moduli reach values up to 10(6) Pa for temperatures of 15 K below the transition. Until now, the mechanical response of the gel was attributed to the elastic interactions of the LC with the colloids. However, the dynamic viscoelastic stiffening with decreasing temperature could not be explained satisfactorily. We used a homemade piezorheometer to measure the complex shear modulus of the sample in parallel plate geometry. Since the applied strains are very small, only the linear viscoelastic regime was tested. This limit guarantees a high degree of reproducibility. We gained insight into the underlying processes by measuring the frequency response for the whole cooling process. Temperature and frequency showed a strong correlation allowing for a superposition of the frequency spectra to form a single master curve similar to time-temperature-superposition. We propose that this superposition behavior is connected to the thermodynamics of the isotropic-nematic phase transition of 5CB located in the network walls. Additional experimental observations, such as hysteresis effects, support this assumption. Morphological aspects were found to be of minor relevance.

Frequency-dependent deformation of liquid crystal droplets in an external electric field.

Nematic droplets suspended in the isotropic phase of the same substance were subjected to alternating electrical fields of varying frequency. To keep the system at a constant nematic/isotropic volume ratio with constant droplet size, we carefully kept the temperature in the isotropic/nematic coexistence region, which was broadened by adding small amounts of a non-mesogenic liquid. Whereas the nematic droplets remained spherical at low (in the order of 10 Hz) and high frequencies (in the order of 1 kHz), at intermediate frequencies we observed a marked flattening of the droplets in the plane perpendicular to the applied field. Droplet deformation occurred both in liquid crystals (LCs) with positive and negative dielectric anisotropy. The experimental data can be quantitatively modelled with a combination of the leaky dielectric model and screening of the applied electric field due to finite conductivity.

Mesospheres in nano-armor: probing the shape-persistence of molten polymer colloids.

We utilize Brillouin light scattering to investigate the shape-persistence of polystyrene-silica core-shell particles by recording their vibrational eigenmodes as a function of temperature. The thin silica shell (tens of nm) protects the polymer core from changing its spherical shape at temperatures above its glass transition temperature Tg, readily obtained from the same experiment. The rigidity of the confined core is enhanced compared to the bare core.

Time-resolved X-ray microscopy of nanoparticle aggregates under oscillatory shear.

Of all the current detection techniques with nanometre resolution, only X-ray microscopy allows imaging of nanoparticles in suspension. Can it also be used to investigate structural dynamics? When studying the response to mechanical stimuli, the challenge lies in its application with a precision comparable with the spatial resolution. In the first shear experiments performed in an X-ray microscope, this has been accomplished by inserting a piezo actuator driven shear cell into the focal plane of a scanning transmission X-ray microscope. Thus shear-induced re-organization of magnetite nanoparticle aggregates could be demonstrated in suspension. As X-ray microscopy proves suitable for studying structural change, new prospects open up in physics at small length scales.

Regulation of mesenchymal stem cell and chondrocyte differentiation by MIA.

Melanoma inhibitory activity (MIA), also referred to as cartilage-derived retinoic acid-sensitive protein (CD-RAP), an 11-kDa secreted protein, is mainly expressed in cartilaginous tissue during embryogenesis and adulthood. Currently, the function of MIA in cartilage tissue is not understood. Here, we describe that MIA acts as a chemotactic factor on the mesenchymal stem cell line C3H10T1/2, stimulating cell migration significantly at concentrations from 0.24 to 240 ng/ml, while inhibiting cell migration at higher doses of 2.4 microg/ml. When analyzing the role of MIA during differentiation processes, we show that MIA by itself is not capable to induce the differentiation of murine or human mesenchymal stem cells. However, MIA influences the action of bone morphogenetic protein (BMP)-2 and transforming growth factor (TGF)-beta 3 during mesenchymal stem cell differentiation, supporting the chondrogenic phenotype while inhibiting osteogenic differentiation. Quantitative RT-PCR analysis revealed the up-regulation of the cartilage markers MIA, collagen type II and aggrecan in human mesenchymal stem cell (HMSC) cultures differentiated in the presence of MIA and TGF-beta 3 or BMP-2 when compared to HMSC cultures differentiated in the presence of TGF-beta 3 or BMP-2 alone. Further, MIA down-regulates gene expression of osteopontin and osteocalcin in BMP-2 treated HMSC cultures inhibiting the osteogenic potential of BMP-2. In the case of human primary chondrocytes MIA stimulates extracellular matrix deposition, increasing the glycosaminoglycan content. Therefore, we postulate that MIA is an important regulator during chondrogenic differentiation and maintenance of cartilage.

Intensity-modulated radiosurgery for childhood arteriovenous malformations.

PURPOSE: Presentation of intensity-modulated radiosurgery (IMRS) for the treatment of inoperable, complex shaped pediatric arterio-venous malformations AVM. METHOD: Between 03/99 and 11/04, IMRS was delivered to seven children aged six to 18 years. Prescribed minimum doses ranged from 17.5 to 20 Gy (median 18 Gy). Radiosurgery planning and delivery used a serial tomotherapeutic IMRT technique (Peacock IMRT, North American Scientific/Nomos, Cranberry Township, PA) over two to four couch angles. A linear accelerator attached binary multi-leaf collimator was used to generate pencil beams of 10 mm by either 8.5 or 4.0 mm. Treatment planning employed an inverse treatment planning optimization algorithm. Parameters submitted to the treatment planning system were: prescription dose (PD), volume of target allowed to receive less dose (standard 3%), minimum dose (0.5 Gy less than PD), and maximum dose (200% of PD). Planning system specific IMRS target and tissue types were selected to prioritize dose conformality over dose homogeneity. The prescription isodose encompassed at least 95% of the target volume. We calculated conformality (CI) and homogeneity indices (HI) to characterize the quality of IMRS plans, and summarized preliminary clinical outcomes. FINDINGS: Target volumes ranged from 0.71 to 63.02 cm(3) (median 13.8 cm(3), 6/7 AVM larger than 10 cm(3)). Median CI was 1.07 (range 1.05 to 1.7) according to RTOG criteria. Median HI was 1.12 (range 1.09 to 1.23). During limited follow-up (median 32 months, range 5 to 53 months), two AVM completely obliterated at 19 and 22 months, and partial obliteration (>75%) was observed in three cases. No treatment-related side effects, other than acute nausea and temporary headaches interpreted as being associated with changes in cerebral blood distribution, were observed. CONCLUSIONS: IMRS can allow for highly conformal planning and delivery of radiosurgery radiation doses even if pediatric AVM target volumes are large and/or highly complex in shape. This technique has been seen to result in favorable preliminary outcomes, thus supporting future exploration of this technique in pediatric and adult patients.

Phase separation in binary fluid mixtures with continuously ramped temperature.

We consider the demixing of a binary fluid mixture, under gravity, which is steadily driven into a two-phase region by slowly ramping the temperature. We assume, as a first approximation, that the system remains spatially isothermal, and we examine the interplay of two competing nonlinearities. One of these arises because the supersaturation is greatest far from the meniscus, creating inversions of the density which can lead to fluid motion; although isothermal, this is somewhat like the Bénard problem (a single-phase fluid heated from below). The other is the intrinsic diffusive instability which results either in nucleation or in spinodal decomposition at large supersaturations. Experimental results on a simple binary mixture show interesting oscillations in heat capacity and optical properties, for a wide range of ramp parameters. We argue that these oscillations arise under conditions where both nonlinearities are important.

The TALON removable head frame system for stereotactic radiosurgery/radiotherapy: measurement of the repositioning accuracy.

PURPOSE: To present the TALON removable head frame system as an immobilization device for single-fraction intensity-modulated stereotactic radiosurgery (IMRS) and fractionated stereotactic intensity-modulated radiotherapy (FS-IMRT); and to evaluate the repositioning accuracy by measurement of anatomic landmark coordinates in repeated computed tomography (CT) examinations. METHODS AND MATERIALS: Nine patients treated by fractionated stereotactic intensity-modulated radiotherapy underwent repeated CTs during their treatment courses. We evaluated anatomic landmark coordinates in a total of 26 repeat CT data sets and respective x, y, and z shifts relative to their positions in the nine treatment-planning reference CTs. An iterative optimization algorithm was employed using a root mean square scoring function to determine the best-fit orientation of subsequent sets of anatomic landmark measurements relative to the original image set. This allowed for the calculation of the x, y, and z components of translation of the target isocenter for each repeat CT. In addition to absolute target isocenter translation, the magnitude (sum vector) of isocenter motion and the patient/target rotation about the three principal axes were calculated. RESULTS: Anatomic landmark analysis over a treatment course of 6 weeks revealed a mean target isocenter translation of 0.95 +/- 0.55, 0.58 +/- 0.46, and 0.51 +/- 0.38 mm in x, y, and z directions, respectively. The mean magnitude of isocenter translation was 1.38 +/- 0.48 mm. The 95% confidence interval ([CI], mean translation plus two standard deviations) for repeated isocenter setup accuracy over the 6-week period was 2.34 mm. Average rotations about the x, y, and z axes were 0.41 +/- 0.36, 0.29 +/- 0.25, and 0.18 +/- 0.15 degrees, respectively. Analysis of the accuracy of the first repeated setup control, representative of single-fraction stereotactic radiosurgery situations, resulted in a mean target isocenter translation in the x, y, and z directions of 0.52 +/- 0.38, 0.56 +/- 0.30, and 0.46 +/- 0.25 mm, respectively. The mean magnitude of isocenter translation was 0.99 +/- 0.28 mm. The 95% confidence interval for these radiosurgery situations was 1.55 mm. Average rotations at first repeated setup control about the x, y, and z axes were 0.24 +/- 0.19, 0.19 +/- 0.17, and 0.19 +/- 0.12 degrees, respectively. CONCLUSION: The TALON relocatable head frame was seen to be well suited for immobilization and repositioning of single-fraction stereotactic radiosurgery treatments. Because of its unique removable design, the system was also seen to provide excellent repeat immobilization and alignment for fractionated stereotactic applications. The exceptional accuracy for the single-fraction stereotactic radiosurgical application of the system was seen to deteriorate only slightly over a 6-week fractionated stereotactic treatment course.

Fulminant radiation-induced necrosis after stereotactic radiation therapy to the posterior fossa. Case report and review of the literature.

The problem of radiation-induced necrosis of normal brain surrounding the target area has been a major catalyst for the development of stereotactically focused radiation therapy. According to current opinion, the effects of stereotactic irradiation are confined to the region targeted. The authors present a case in which the administration of a conventional dose of stereotactically focused irradiation for treatment of a pilocytic astrocytoma produced fulminant necrosis that necessitated a combination of intensive surgical and medical management, after which the patient improved over the course of 1 year. Concomitant with his improvement, the initially remarkable findings on magnetic resonance imaging gradually resolved. In this presentation the authors emphasize the need to evaluate alternatives carefully before a decision is made to administer therapeutic irradiation. Furthermore, they explore the roles that target, host, and dosage factors play in hypersensitivity to radiation injury, the detection of these factors before treatment, and the administration of radioprotective agents. With the growing use of stereotactically focused irradiation as a primary treatment modality for a variety of neurosurgical conditions, it is important to be cognizant of its uncommon but potentially lethal side effects. A cooperative multicenter database in which the outcomes and morbidity following stereotactic irradiation are recorded is essential to the detection of relatively uncommon but severe complications such as those observed in this case.

Bone loading pattern around implants in average and atrophic edentulous maxillae: a finite-element analysis.

INTRODUCTION: Oral implants placed in the maxilla, especially the posterior region, have a lower success rate than those placed in the mandible. Poor bone quantity and quality have been suggested as a reason for this differential success rate. OBJECTIVE: The purpose of this study was, therefore, to evaluate stress and strain distributions around loaded implants in the normal and atrophic maxilla by finite-element (FE) analyses. MATERIAL: FE models of a solitary implant were generated to determine stresses and strains in the bone adjacent to the implant surface under loading conditions. STUDY DESIGN: Different bony situations and implant lengths were used in a FE model. Static loads were applied axially and the resulting stresses and strains calculated. RESULTS: Bone quality and quantity play a major role in decreasing bone strains adjacent to the implant surface under loading. It was found that stresses were more homogeneously distributed when more spongy bone was present. Decreased bone height was found to have less pronounced effects on strain and stress alterations than poor bone quality. Atrophic bony dimensions in combination with poor bone quality were associated with surface strains exceeding physiological levels (> 6,000 microstrains). CONCLUSION: Our investigation indicates that supraphysiological bone strains adjacent to the implant surface should be expected under mechanical loading in the atrophic maxilla.

[Planning orthodontic surgery with the Hexapod system]. / Planung orthognather Chirurgie mit dem Hexapod.

Treatment of maxillofacial dysgnathia using a combined surgical/orthodontic approach requires careful orthodontic and orthognathic diagnosis and treatment planning. In the present study, a system enabling on-line presentation of the necessary displacements of the jaw during surgery, while improving the accuracy of the planning, is described. Using the hexapod principle, it is possible to plan operations with six degrees of freedom and to measure the three-dimensional movements of jaws and jaw segments within the planning stage. Routinely prepared casts are employed for simulation of the operation. The displacements of the jaw are presented in a manner familiar to the orthodontic surgeon, namely in a surgical record. The accuracy achieved with the hexapod is superior to that achievable intra-operatively.

Multiple-revolution spiral osteotomy for cranial reconstruction. Technical note.

Various combinations of cranial remodeling techniques are used in an attempt to provide optimal cosmetic results and to reduce possible sequelae associated with craniosynostosis. One element of deformity that is difficult to correct directly is an overly flattened area such as that found in the parietal area in sagittal synostosis, unilaterally in lambdoid synostosis, or even in severe positional molding. The authors present a novel application for recontouring cranial bone, namely the multiple-revolution spiral osteotomy. The advantages of this technique include the avoidance of large areas of craniectomy and immediate correction of the cranial deformity. The surgical procedure, illustrative cases, early results, and apparent benefits of this technique are discussed.

Antimicrobial resistance and bacterial identification utilizing a microelectronic chip array.

Species-specific bacterial identification of clinical specimens is often limited to a few species due to the difficulty of performing multiplex reactions. In addition, discrimination of amplicons is time-consuming and laborious, consisting of gel electrophoresis, probe hybridization, or sequencing technology. In order to simplify the process of bacterial identification, we combined anchored in situ amplification on a microelectronic chip array with discrimination and detection on the same platform. Here, we describe the simultaneous amplification and discrimination of six gene sequences which are representative of different bacterial identification assays: Escherichia coli gyrA, Salmonella gyrA, Campylobacter gyrA, E. coli parC, Staphylococcus mecA, and Chlamydia cryptic plasmid. The assay can detect both plasmid and transposon genes and can also discriminate strains carrying antibiotic resistance single-nucleotide polymorphism mutations. Finally, the assay is similarly capable of discriminating between bacterial species through reporter-specific discrimination and allele-specific amplification. Anchored strand displacement amplification allows multiplex amplification and complex genotype discrimination on the same platform. This assay simplifies the bacterial identification process greatly, allowing molecular biology techniques to be performed with minimal processing of samples and practical experience.

Mechanical tension in distraction osteogenesis regulates chondrocytic differentiation.

Differentiation of chondrocytes to cells of osteoblastic phenotype occurs during an interim period of bone development, fracture repair and distraction osteogenesis. To study the relationship between tension-stress and chondrogenesis, uniaxial strains (0 microstrains, 2000 microstrains, 20000 microstrains, 200000 microstrains, 300000 microstrains) were applied in a rabbit model of mandibular distraction osteogenesis. The results demonstrated that cell differentiation, apoptosis and tissue development in the newly formed gap tissue showed a correlation to the applied strain magnitudes. Only strains of 20000 microstrains resulted in a statistically significant (P<0.05) formation of cartilage struts with embedded chondrocyte-like cells. However, chondrocyte-like cells were rarely detected in samples distracted at lower or higher strain magnitudes. Osteoblasts appeared to replace cartilaginous matrix by mineralized bone matrix. The phenotypic change from chondrocytes to osteoblasts was accompanied by a decreased proteoglycan synthesis. a change in the expression from type II collagen towards type I and involved asymmetric cell divisions and apoptotic cell death. Therefore, we suggest that mechanical strain is an external stimulus responsible for phenotypic cell alterations.

Experimental and finite element study of a human mandible.

Knowledge of the complex biomechanical behaviour of the human mandible is of great importance in various clinical situations. Various approaches can be used to evaluate the physical behaviour of bony specimens. In the course of this study, we investigated mandibular deformation under mechanical loads in an experimental setting and compared them with results derived from finite element analysis (FEA). A special apparatus was developed to apply various forces under defined conditions on an explanted human mandible in vitro. Strains on the surface of the mandible were measured with strain gauges and subsequently a voxel based finite element mesh was generated. Strain patterns of the mandible were calculated in the FE analysis and matched with the experimental data. Comparing the numerical with the experimental data, we found a good correlation between in vitro measurements and mathematical modelling (correlation coefficient = 0.992). Then the FE model was used to evaluate mandibular biomechanics relative to aspects of load transfer, stress distribution and displacements. It is concluded that the applied procedure of generating the FE model is a valid and accurate, non-invasive method to predict different parameters of the complex biomechanical behaviour of human mandibles.

Application of bone remodeling theories in the simulation of orthodontic tooth movements.

A numerical model that calculates bone apposition and resorption around a tooth root on the basis of bone remodeling theories was developed to simulate orthodontic tooth movements. The model was used to calculate different kinds of orthodontic tooth movements, that were then compared with the expected movements based on clinical experience. For simulation of the movements the root of a canine was modeled in an idealized way in the form of an elliptical paraboloid and was processed with a finite element program. The finite element model was loaded with defined force systems. Two model assumptions were used to calculate the bone remodeling process. The mechanical loads firstly in the periodontal ligament and secondly in the alveolar bone were taken to simulate the following tooth movements: 1. mesial tipping around the center of resistance (force system at the bracket: isolated torque MY = 5 Nmm), 2. rotation around the long axis of the tooth (MZ = 5 Nmm), 3. uncontrolled tipping around the root tip (FX = 1 N, MZ = 5 Nmm), 4. canine retraction (FX = 1 N, MY = -9.5 Nmm, MZ = 5 Nmm), 5. and 6. extrusion/intrusion (FZ = +/- 0.5 N, MX = +/- 2.5 Nmm). Comparison with clinical experience was performed by calculating the orthodontic tooth movements based on the assumption of a fixed position of the center of resistance. It could be demonstrated that the numerical model of orthodontic bone remodeling can be used to calculate orthodontic tooth movements. However, the results are strongly dependent on the model assumptions. The model simulating the bone remodeling on the basis of the loading of the periodontal ligament delivers results that are in very good accordance with the biomechanical assumptions of the position of the center of resistance. However, marked side effects occurred with the second model, especially in the simulations of uncontrolled tipping, translation and intrusion/extrusion. Clinically, these side effects cannot be observed.

[Effect of implant geometry on strain distribution in peri-implant bone]. / Einfluss der Implantatgeometrie auf die Strainverteilung im periimplantären Knochen.

Recent developments and results in the field of mechanical bone stimulation have made it possible to define limits between physiological and non-physiological transmission of strength to the bone. Now it is necessary to investigate the different geometries of dental implants regarding biomechanical reliability. The aim of this study was to examine the distribution of strain on the bone along different basic forms of implants during loading using finite element analysis (FEA). The following implant designs were included in the study: cylinder, threaded cylinder, cylinder with steps, threaded cylinder with steps, and double-disk implants. All implants had a length of 12 mm and a diameter of 4 mm, the axial loading was defined as 300 N. Threaded implants showed more homogeneous distribution of strain than stepped implants, however, the maximum values were below the physiological range. Shortening of the implants led to an increase of the values, however, there was a zone of hypophysiological strain apically. Disk implants showed extremely low values at the disk margins, possibly due to the lack of physiological bone stimulus by the disks. Overall, none of the implants showed optimal distribution of strain, even though homogeneous strain distribution is decisive for long-term implant stability.

[Semi-automatic generation of finite element meshes fo dental preparations]. / Halbautomatische Generierung von Finite-Element-Netzen zahnmedizinischer Präparate.

The mechanical properties and elastic behaviour of periodontal tissue are a decisive factor in understanding initial tooth mobility and bone remodelling processes in orthodontics. An experimental set-up was designed to precisely determine a tooth's elastic response to different loading conditions. Segments of pig's maxilla bearing separated molars were used, and their mechanical response to loading was recorded. Subsequently, finite element analysis (FEA) was performed on the basis of the experimental data. The combination of experimental and numerical methods was used to determine the material properties of the periodontal ligament (PDL). The geometries of the preparations were reconstructed and FE meshes generated semi-automatically with the aid of the special computer program, CAGOG (Computer Aided Generator for Orthodontic Geometries) to optimally match the experimental geometry. Nonlinear material parameters were determined for the PDL and verified by comparing experimental and numerical results obtained in other specimens with an error of about 10%. This good correlation indicates that the selected method of mesh generation is appropriate for creating realistic FE models that can be compared with experimental results.