Species-specific homing mechanisms of human prostate cancer metastasis in tissue engineered bone

The development of effective therapeutic strategies against prostate cancer bone metastases has been impeded by the lack of adequate animal models that are able to recapitulate the biology of the disease in humans. Bioengineered approaches allow researchers to create sophisticated experimentally and physiologically relevant in vivo models to study interactions between cancer cells and their microenvironment under reproducible conditions. The aim of this study was to engineer a morphologically and functionally intact humanized organ bone which can serve as a homing site for human prostate cancer cells. Transplantation of biodegradable tubular composite scaffolds seeded with human mesenchymal progenitor cells and loaded with rhBMP-7 resulted in the development of a chimeric bone construct including a large number of human mesenchymal cells which were shown to be metabolically active and capable of producing extracellular matrix components. Micro-CT analysis demonstrated that the newly formed ossicle recapitulated the morphological features of a physiological organ bone with a trabecular network surrounded by a cortex-like outer structure. This microenvironment was supportive of the lodgement and maintenance of murine haematopoietic cell clusters, thus mimicking a functional organ bone. Bioluminescence imaging demonstrated that luciferase-transduced human PC3 cells reproducibly homed to the humanized tissue engineered bone constructs, proliferated, and developed macro-metastases. This model allows the analysis of interactions between human prostate cancer cells and a functional humanized bone organ within an immuno-incompetent murine host. The system can serve as a reproducible platform to study effects of therapeutics against prostate cancer bone metastases within a humanized microenvironment.

Interactions between organizational culture, trustworthiness, and mechanisms for inter-project knowledge sharing

This research used a multiple-case study approach to empirically investigate the complex relationship between factors influencing inter-project knowledge sharing—trustworthiness, organizational culture, and knowledge-sharing mechanisms. Adopting a competing values framework, we found evidence of patterns existing between the type of culture, on the project management unit level, and project managers’ perceptions of valuing trustworthy behaviors and the way they share knowledge, on the individual level. We also found evidence for mutually reinforcing the effect of trust and clan culture, which shape tacit knowledge-sharing behaviors.

Exploration of mechanisms underlying the strain-rate-dependent mechanical property of single chondrocytes

Based on the characterization by Atomic Force Microscopy (AFM), we report that the mechanical property of single chondrocytes has dependency on the strain-rates. By comparing the mechanical deformation responses and the Young’s moduli of living and fixed chondrocytes at four different strain-rates, we explore the deformation mechanisms underlying this dependency property. We found that the strain-rate-dependent mechanical property of living cells is governed by both of the cellular cytoskeleton (CSK) and the intracellular fluid when the fixed chondrocytes is mainly governed by their intracellular fluid which is called the consolidation-dependent deformation behavior. Finally, we report that the porohyperelastic (PHE) constitutive material model which can capture the consolidation-dependent behavior of both living and fixed chondrocytes is a potential candidature to study living cell biomechanics.

Mechanisms of glycerol dehydration

Dehydration of neutral and protonated glycerol was investigated using quantum mechanical calculations (CBS-QB3). Calculations on neutral glycerol show that there is a high barrier for simple 1,2-dehydration, E-a = 70.9 kcal mol(-1), which is lowered to 65.2 kcal mol(-1) for pericyclic 1,3-dehydration. In contrast, the barriers for dehydration of protonated glycerol are much lower. Dehydration mechanisms involving hydride transfer, pinacol rearrangement, or substitution reactions have barriers between 20 and 25 kcal mol(-1). Loss of water from glycerol via substitution results in either oxirane or oxetane intermediates, which can interconvert over a low barrier. Subsequent decomposition of these intermediates proceeds via either a second dehydration step or loss of formaldehyde. The computed mechanisms for decomposition of protonated glycerol are supported by the gas-phase fragmentation of protonated glycerol observed using a triple-quadrupole mass spectrometer.

Innovating urban policymaking and planning mechanisms to deliver knowledge-based agendas : a methodological approach

This paper aims to develop a comprehensive approach to innovate urban policymaking and planning to successfully deliver the knowledge-based agenda. The paper, first, examines the concept of knowledge-based urban development, which has become a popular urban development policy and strategy in recent years, through a comprehensive review of the literature. It, then, introduces and discusses a novel methodological approach for effective policymaking and planning mechanism to deliver the knowledge-based agenda of cities. The paper, with the proposed methodology, brings together urban policymaking and planning approaches, and introduces a novel way to assess knowledge-based urban development achievements and potentials of emerging and prosperous knowledge cities. The paper, thus, provides an invaluable instrument to inform local and regional decision and plan making mechanisms to deliver their knowledge-based agendas and help them in moving towards building their sustainable knowledge cities.

Mechanisms of tumour invasion and metastasis : emerging targets for therapy

The progression of a tumour from one of benign and delimited growth to one that is invasive and metastatic is the major cause of poor clinical outcome in cancer patients. The invasion and metastasis of tumours is a highly complex and multistep process that requires a tumour cell to modulate its ability to adhere, degrade the surrounding extracellular matrix, migrate, proliferate at a secondary site and stimulate angiogenesis. Knowledge of the process has greatly increased and this has resulted in the identification of a number of molecules that are fundamental to the process. The involvement of these molecules has been shown to relate not only to the survival and proliferation of the tumour cell but, also to the processes of tumour cell adhesion, migration, and the tumour cells ability to degrade and escape the primary site as well as play a role in angiogenesis. These molecules may provide important therapeutic targets that represent the ability to target specific steps in the process of invasion and metastasis and provide additional therapies. The review focuses on representative key targets in each of these processes and summarises the state of play in each case.

A qualitative investigation of adolescents’ perceived mechanisms of change from a universal school-based depression prevention program

A recent meta-analysis provides evidence supporting the universal application of school-based prevention programs for adolescent depression. The mechanisms underlying such successful interventions, however, are largely unknown. We report on a qualitative analysis of 109 Grade 9 students’ beliefs about what they gained from an evidence-based depression prevention intervention, the Resourceful Adolescent Program (RAP-A). Fifty-four percent of interviewees articulated at least one specific example of program benefit. A thematic analysis of responses revealed two major themes, improved interpersonal relationships and improved self-regulation, both stronger than originally assumed. A more minor theme also emerged—more helpful cognitions. It is postulated that both improved interpersonal relationships and improved self-regulation are likely to enhance one another, and more helpful cognitions may express its contribution through enhanced self-regulation. These findings broaden our understanding of the impact of depression prevention programs, beginning to illuminate how such programs benefit participants.

Mechanisms of change in psychotherapy for people diagnosed with schizophrenia : the role of narrative reflexivity in promoting recovery

Narrative reflexivity was investigated as a potential mechanism of therapeutic change during a 12 - 18 month trial of Metacognitive Narrative Psychotherapy for people diagnosed with schizophrenia. Participants were nine adult clients (8 male, 1 female) aged between 25-65 years (M = 44, SD = 12.76) with a diagnosis of schizophrenia consistent with DSM-IV criteria and seven female provisional psychologists aged between 25-29 years (M = 26.8 years, SD = 1.47 years). Recovery and narrative reflexivity were measured at three time points using the Recovery Assessment Scale (RAS) and the Narrative Processes Coding System (NPCS). Results were reported descriptively due to limited sample size (n = 9). The majority of clients (n = 7) reported an increase in recovery over the course of treatment. For six clients, an overall increase in recovery was associated with an increase in narrative reflexivity. This study provides preliminary support for narrative reflexivity as a potential mechanism of therapeutic change in the psychotherapy of people diagnosed with schizophrenia.

Carbon nanorods and graphene-like nanosheets by hot filament CVD : growth mechanisms and electron field emission

Carbon nanorods and graphene-like nanosheets are catalytically synthesized in a hot filament chemical vapor deposition system with and without plasma enhancement, with gold used as a catalyst. The morphological and structural properties of the carbon nanorods and nanosheets are investigated by field-emission scanning electron microscopy, transmission electron microscopy and micro-Raman spectroscopy. It is found that carbon nanorods are formed when a CH4 + H2 + N2 plasma is present while carbon nanosheets are formed in a methane environment without a plasma. The formation of carbon nanorods and carbon nanosheets are analyzed. The results suggest that the formation of carbon nanorods is primarily a precipitation process while the formation of carbon nanosheets is a complex process involving surface-catalysis, surface diffusion and precipitation influenced by the Gibbs–Thomson effect. The electron field emission properties of the carbon nanorods and graphene-like nanosheets are measured under high-vacuum; it is found that the carbon nanosheets have a lower field emission turn-on than the carbon nanorods. These results are important to improve the understanding of formation mechanisms of carbon nanomaterials and contribute to eventual applications of these structures in nanodevices.

Proteins, drug targets and the mechanisms they control : the simple truth about complex networks

Realizing the promise of molecularly targeted inhibitors for cancer therapy will require a new level of knowledge about how a drug target is wired into the control circuitry of a complex cellular network. Here we review general homeostatic principles of cellular networks that enable the cell to be resilient in the face of molecular perturbations, while at the same time being sensitive to subtle input signals. Insights into such mechanisms may facilitate the development of combination therapies that take advantage of the cellular control circuitry, with the aim of achieving higher efficacy at a lower drug dosage and with a reduced probability of drug-resistance development.

Temperature-dependent growth mechanisms of low-dimensional ZnO nanostructures

One-dimensional ZnO nanostructures were successfully synthesized on single-crystal silicon substrates via a simple thermal evaporation and vapour-phase transport method under different process temperatures from 500 to 1000 °C. The detailed and in-depth analysis of the experimental results shows that the growth of ZnO nanostructures at process temperatures of 500, 800, and 1000 °C is governed by different growth mechanisms. At a low process temperature of 500 °C, the ZnO nanostructures feature flat and smooth tips, and their growth is primarily governed by the vapour-solid mechanism. At an intermediate process temperature of 800 °C, the ZnO nanostructures feature cone-shape tips, and their growth is primarily governed by the self-catalyzed and saturated vapour–liquid–solid mechanism. At a high process temperature of 1000 °C, the alloy tip appears on the front side of the ZnO nanostructures, and their growth is primarily governed by the common catalyst-assisted vapour–liquid–solid mechanism. It is also shown that the morphological, structural, optical, and compositional properties of the synthesized ZnO nanostructures are closely related to the process temperature. These results are highly relevant to the development of light-emitting diodes, chemical sensors, energy conversion devices, and other advanced applications.

Controlled electronic transport in single-walled carbon nanotube networks : selecting electron hopping and chemical doping mechanisms

The electronic transport in both intrinsic and acid-treated single-walled carbon nanotube networks containing more than 90% semiconducting nanotubes is investigated using temperature-dependent resistance measurements. The semiconducting behavior observed in the intrinsic network is attributed to the three-dimensional electron hopping mechanism. In contrast, the chemical doping mechanism in the acid-treated network is found to be responsible for the revealed metal-like linear resistivity dependence in a broad temperature range. This effective method to control the electrical conductivity of single-walled carbon nanotube networks is promising for future nanoscale electronics, thermometry, and bolometry. © 2010 American Institute of Physics.

Mechanisms of sulfide ion oxidation during cyanidation. Part II : Surface catalysis by pyrite

The mechanisms and the reaction products for the oxidation of sulfide ions in the presence of pyrite have been established. When the leach solution contains free sulfide ions, oxidation occurs via electron transfer from the sulfide ion to dissolved oxygen on the pyrite mineral surface, with polysulfides being formed as an intermediate oxidation product. In the absence of cyanide, the polysulfides are further oxidised to thiosulfate, whilst with cyanide present, thiocyanate and sulfite are also formed from the reaction of polysulfides with cyanide and dissolved oxygen. Polysulfide chain length has been shown to affect the final reaction products of polysulfide oxidation by dissolved oxygen. The rate of pyrite catalysed sulfide ion oxidation was found to be slower in cyanide solutions compared to cyanide free solutions. Mixed potential measurements indicated that the reduction of oxygen at the pyrite surface is hindered in the presence of cyanide. The presence of sulfide ions was also found to activate the pyrite surface, increasing its rate of oxidation by oxygen. This effect was particularly evident in the presence of cyanide; in the presence of sulfide the increase in total sulfur from pyrite oxidation was 2.3 mM in 7 h, compared to an increase of <1 mM in the absence of sulfide over 24 h.

A meshfree particle based model for microscale shrinkage mechanisms of food materials in drying conditions

Cells are the fundamental building block of plant based food materials and many of the food processing born structural changes can fundamentally be derived as a function of the deformations of the cellular structure. In food dehydration the bulk level changes in porosity, density and shrinkage can be better explained using cellular level deformations initiated by the moisture removal from the cellular fluid. A novel approach is used in this research to model the cell fluid with Smoothed Particle Hydrodynamics (SPH) and cell walls with Discrete Element Methods (DEM), that are fundamentally known to be robust in treating complex fluid and solid mechanics. High Performance Computing (HPC) is used for the computations due to its computing advantages. Comparing with the deficiencies of the state of the art drying models, the current model is found to be robust in replicating drying mechanics of plant based food materials in microscale.

Mechanisms of mono- and poly-ubiquitination : ubiquitination specificity depends on compatibility between the E2 catalytic core and amino acid residues proximal to the lysine

Ubiquitination involves the attachment of ubiquitin to lysine residues on substrate proteins or itself, which can result in protein monoubiquitination or polyubiquitination. Ubiquitin attachment to different lysine residues can generate diverse substrate-ubiquitin structures, targeting proteins to different fates. The mechanisms of lysine selection are not well understood. Ubiquitination by the largest group of E3 ligases, the RING-family E3 s, is catalyzed through co-operation between the non-catalytic ubiquitin-ligase (E3) and the ubiquitin-conjugating enzyme (E2), where the RING E3 binds the substrate and the E2 catalyzes ubiquitin transfer. Previous studies suggest that ubiquitination sites are selected by E3-mediated positioning of the lysine toward the E2 active site. Ultimately, at a catalytic level, ubiquitination of lysine residues within the substrate or ubiquitin occurs by nucleophilic attack of the lysine residue on the thioester bond linking the E2 catalytic cysteine to ubiquitin. One of the best studied RING E3/ E2 complexes is the Skp1/Cul1/F box protein complex, SCFCdc4, and its cognate E2, Cdc34, which target the CDK inhibitor Sic1 for K48-linked polyubiquitination, leading to its proteasomal degradation. Our recent studies of this model system demonstrated that residues surrounding Sic1 lysines or lysine 48 in ubiquitin are critical for ubiquitination. This sequence-dependence is linked to evolutionarily conserved key residues in the catalytic region of Cdc34 and can determine if Sic1 is mono- or poly-ubiquitinated. Our studies indicate that amino acid determinants in the Cdc34 catalytic region and their compatibility to those surrounding acceptor lysine residues play important roles in lysine selection. This may represent a general mechanism in directing the mode of ubiquitination in E2 s.