Mesenchymal stem cells

Cell based therapies as they apply to tissue engineering and regenerative medicine, require cells capable of self renewal and differentiation, and a prerequisite is to be able to prepare an effective dose of ex vivo expanded cells for autologous transplants. The in vivo identification of a source of physiologically relevant cell types suitable for cell therapies therefore figures as an integral part of tissue engineering. Stem cells serve as a reserve for biological repair, having the potential to differentiate into a number of specialised cell types within the body; they therefore represent the most useful candidates for cell based therapies. The primary goal of stem cell research is to produce cells that are both patient specific, as well as having properties suitable for the specific conditions for which they are intended to remedy. From a purely scientific perspective, stem cells allow scientists to gain a deeper understanding of developmental biology and regenerative therapies. Stem cells have acquired a number of uses for applications in regenerative medicine, immunotherapy, gene therapy, but it is in the area of tissue engineering that they generate most excitement, primarily as a result of their capacity for self-renewal and pluripotency. A unique feature of stem cells is their ability to maintain an uncommitted quiescent state in vivo and then, once triggered by conditions such as disease, injury or natural wear or tear, serve as a reservoir and natural support system to replenish lost cells. Although these cells retain the plasticity to differentiate into various tissues, being able to control this differentiation process is still one of the biggest challenges facing stem cell research. In an effort to harness the potential of these cells a number of studies have been conducted using both embryonic/foetal and adult stem cells. The use of embryonic stem cells (ESC) have been hampered by strong ethical and political concerns, this despite their perceived versatility due to their pluripotency. Ethical issues aside, other concerns raised with ESCs relates to the possibility of tumorigenesis, immune rejection and complications with immunosuppressive therapies, all of which adds layers of complications to the application ESC in research and which has led to the search for alternative sources for stem cells. The adult tissues in higher organisms harbours cells, termed adult stem cells, and these cells are reminiscent of unprogrammed stem cells. A number of sources of adult stem cells have been described. Bone marrow is by far the most accessible source of two potent populations of adult stem cells, namely haematopoietic stem cells (HSCs) and bone marrow mesenchymal stem cells (BMSCs). Autologously harvested adult stem cells can, in contrast to embryonic stem cells, readily be used in autografts, since immune rejection is not an issue; and their use in scientific research has not attracted the ethical concerns which have been the case with embryonic stem cells. The major limitation to their use, however, is the fact that adult stem cells are exceedingly rare in most tissues. This fact makes identifying and isolating these cells problematic; bone marrow being perhaps the only notable exception. Unlike the case of HSCs, there are as yet no rigorous criteria for characterizing MSCs. Changing acuity about the pluripotency of MSCs in recent studies has expanded their potential application; however, the underlying molecular pathways which impart the features distinctive to MSCs remain elusive. Furthermore, the sparse in vivo distribution of these cells imposes a clear limitation to their study in vitro. Also, when MSCs are cultured in vitro, there is a loss of the in vivo microenvironment, resulting in a progressive decline in proliferation potential and multipotentiality. This is further exacerbated with increased passage numbers in culture, characterized by the onset of senescence related changes. As a consequence, it is necessary to establish protocols for generating large numbers of MSCs but without affecting their differentiation potential. MSCs are capable of differentiating into mesenchymal tissue lineages, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Recent findings indicate that adult bone marrow may also contain cells that can differentiate into the mature, nonhematopoietic cells of a number of tissues, including cells of the liver, kidney, lung, skin, gastrointestinal tract, and myocytes of heart and skeletal muscle. MSCs can readily be expanded in vitro and can be genetically modified by viral vectors and be induced to differentiate into specific cell lineages by changing the microenvironment–properties which makes these cells ideal vehicles for cellular gene therapy. MSCs can also exert profound immunosuppressive effects via modulation of both cellular and innate immune pathways, and this property allows them to overcome the issue of immune rejection. Despite the many attractive features associated with MSCs, there are still many hurdles to overcome before these cells are readily available for use in clinical applications. The main concern relates to in vivo characterization and identification of MSCs. The lack of a universal biomarker, sparse in vivo distribution, and a steady age related decline in their numbers, makes it an obvious need to decipher the reprogramming pathways and critical molecular players which govern the characteristics unique to MSCs. This book presents a comprehensive insight into the biology of adult stem cells and their utility in current regeneration therapies. The adult stem cell populations reviewed in this book include bone marrow derived MSCs, adipose derived stem cells (ASCs), umbilical cord blood stem cells, and placental stem cells. The features such as MSC circulation and trafficking, neuroprotective properties, and the nurturing roles and differentiation potential of multiple lineages have been discussed in details. In terms of therapeutic applications, the strengths of MSCs have been presented and their roles in disease treatments such as osteoarthritis, Huntington’s disease, periodontal regeneration, and pancreatic islet transplantation have been discussed. An analysis comparing osteoblast differentiation of umbilical cord blood stem cells and MSCs has been reviewed, as has a comparison of human placental stem cells and ASCs, in terms of isolation, identification and therapeutic applications of ASC in bone, cartilage regeneration, as well as myocardial regeneration. It is my sincere hope that this book will update the reader as to the research progress of MSC biology and potential use of these cells in clinical applications. It will be the best reward to all contributors of this book, if their efforts herein may in some way help the readers in any part of their study, research, and career development.

Technical report : acoustic analysis of the natural environment

This technical report is concerned with one aspect of environmental monitoring—the detection and analysis of acoustic events in sound recordings of the environment. Sound recordings offer ecologists the advantage of cheaper and increased sampling but make available so much data that automated analysis becomes essential. The report describes a number of tools for automated analysis of recordings, including noise removal from spectrograms, acoustic event detection, event pattern recognition, spectral peak tracking, syntactic pattern recognition applied to call syllables, and oscillation detection. These algorithms are applied to a number of animal call recognition tasks, chosen because they illustrate quite different modes of analysis: (1) the detection of diffuse events caused by wind and rain, which are frequent contaminants of recordings of the terrestrial environment; (2) the detection of bird and calls; and (3) the preparation of acoustic maps for whole ecosystem analysis. This last task utilises the temporal distribution of events over a daily, monthly or yearly cycle.

Single crystal Raman spectroscopy of natural leiteite ZnAs2O4 and in comparison with the synthesised mineral

The oriented single crystal Raman spectrum of leiteite has been obtained and the spectra related to the structure of the mineral. The intensities of the observed bands vary according to orientation allowing them to be assigned to either Ag or Bg modes. Ag bands are generally the most intense in the CAAC spectrum, followed by ACCA, CBBC, and ABBA whereas Bg bands are generally the most intense in the CBAC followed by ABCA. The CAAC and ACCA spectra are identical, as are those obtained in the CBBC and ABBA orientations. Both cross-polarised spectra are identical. Band assignments were made with respect to bridging and non-bridging As-O bonds.

Single-crystal Raman spectroscopy of natural schafarzikite FeSb2O4 from Pernek, Slovak Republic

The single crystal Raman spectra of natural mineral schafarzikite FeSb2O4 from the Pernek locality of the Slovak Republic are presented for the first time. Raman spectra of natural mineral apuanite Fe2+Fe43+Sb4O12S, originating from the Apuan Alps in Italy, as well as spectra of synthetic ZnSb2O4 and arsenite mineral trippkeite CuAs2O4 are also presented for the first time. The spectra of the antimonite minerals are characterized by a strong band in the region 660 – 680 cm-1 with shoulders on either side, and a band of medium intensity near 300 cm-1. The spectrum of the arsenite mineral is characterized by a medium band near 780 cm-1 with a shoulder on the high wavenumber side and a strong band at 370 cm-1. Assignments are proposed based on the spectral comparison between the compounds, symmetry modes of the bands and prior literature. The single crystal spectra of schafarzikite showed good mode separation, allowing bands to be assigned a symmetry species of A1g, B1g, B2g or Eg.

Nursing and competencies - a natural fit : the politics of skill/competency formation in nursing

The last two decades have seen a significant restructuring of work across Australia and other industrialised economies, a critical part of which has been the appearance of competency based education and assessment. The competency movement is about creating a more flexible and mobile labour force to increase productivity and it does so by redefining work as a set of transferable or ‘soft’ generic skills that are transportable and are the possession of the individual. This article sought to develop an analysis of competency based clinical assessment of nursing students across a bachelor of nursing degree course. This involved an examination of a total of 406 clinical assessment tools that covered the years 1992-2009 and the three years of a bachelor degree. Data analysis generated three analytical findings: the existence of a hierarchy of competencies that prioritises soft skills over intellectual and technical skills; the appearance of skills as personal qualities or individual attributes; and the absence of context in assessment. The article argues that the convergence in nursing of soft skills and the professionalisation project reform has seen the former give legitimacy to the enduring invisibility and devaluation of nursing work.

Natural and engineered kallikrein inhibitors: an emerging pharmacopoeia

The kallikreins and kallikrein-related peptidases are serine proteases that control a plethora of developmental and homeostatic phenomena, ranging from semen liquefaction to skin desquamation and blood pressure. The diversity of roles played by kallikreins has stimulated considerable interest in these enzymes from the perspective of diagnostics and drug design. Kallikreins already have well-established credentials as targets for therapeutic intervention and there is increasing appreciation of their potential both as biomarkers and as targets for inhibitor design. Here, we explore the current status of naturally occurring kallikrein protease-inhibitor complexes and illustrate how this knowledge can interface with strategies for rational re-engineering of bioscaffolds and design of small-molecule inhibitors.

Unsteady natural convection in a triangular enclosure under isothermal heating

The fluid flow and heat transfer inside a triangular enclosure due to instantaneous heating on the inclined walls are investigated using an improved scaling analysis and direct numerical simulations. The development of the unsteady natural convection boundary layer under the inclined walls may be classified into three distinct stages including a start-up stage, a transitional stage and a steady state stage, which can be clearly identified in the analytical and numerical results. A new triple-layer integral approach of scaling analysis has been considered to obtain major scaling relations of the velocity, thicknesses, Nusselt number and the flow development time of the natural convection boundary layer and verified by direct numerical simulations over a wide range of flow parameters.

Scaling of natural convection of an inclined flat plate : ramp cooling condition

A scaling analysis is performed for the transient boundary layer established adjacent to an inclined flat plate following a ramp cooling boundary condition. The imposed wall temperature decreases linearly up to a specific value over a specific time. It is revealed that if the ramp time is sufficiently large then the boundary layer reaches quasi-steady mode before the growth of the temperature is finished. However, if the ramp time is shorter then the steady state of the boundary layer may be reached after the growth of the temperature is completed. In this case, the ultimate steady state is the same as if the start up had been instantaneous. Note that the cold boundary layer adjacent to the plate is potentially unstable to Rayleigh-Bénard instability if the Rayleigh number exceeds a certain critical value for this cooling case. The onset of instability may set in at different stages of the boundary layer development. A proper identification of the time when the instability may set in is discussed. A numerical verification of the time for the onset of instability is presented in this study. Different flow regimes based on the stability of the boundary layer have also been discussed with numerical results.

Natural convection boundary-layer adjacent to an inclined flat plate subject to sudden and ramp heating

The natural convection thermal boundary layer adjacent to an inclined flat plate subject to sudden heating and a temperature boundary condition which follows a ramp function up until a specified time and then remains constant is investigated. The development of the flow from start-up to a steady-state has been described based on scaling analyses and verified by numerical simulations. Different flow regimes based on the Rayleigh number are discussed with numerical results for both boundary conditions. For ramp heating, the boundary layer flow depends on the comparison of the time at which the ramp heating is completed and the time at which the boundary layer completes its growth. If the ramp time is long compared with the steady state time, the layer reaches a quasi steady mode in which the growth of the layer is governed solely by the thermal balance between convection and conduction. On the other hand, if the ramp is completed before the layer becomes steady; the subsequent growth is governed by the balance between buoyancy and inertia, as for the case of instantaneous heating.

Scaling of natural convection of an inclined flat plate : sudden cooling condition

The natural convection boundary layer adjacent to an inclined plate subject to sudden cooling boundary condition has been studied. It is found that the cold boundary layer adjacent to the plate is potentially unstable to Rayleigh-Bénard instability if the Rayleigh number exceeds a certain critical value. A scaling relation for the onset of instability of the boundary layer is achieved. The scaling relations have been developed by equating important terms of the governing equations based on the development of the boundary layer with time. The flow adjacent to the plate can be classified broadly into a conductive, a stable convective or an unstable convective regime determined by the Rayleigh number. Proper scales have been established to quantify the flow properties in each of these flow regimes. An appropriate identification of the time when the instability may set in is discussed. A numerical verification of the time for the onset of instability is also presented in this study. Different flow regimes based on the stability of the boundary layer have been discussed with numerical results.

Natural convection in attic-shaped spaces subject to sudden and ramp heating boundary conditions

In this study, a discussion of the fluid dynamics in the attic space is reported, focusing on its transient response to sudden and linear changes of temperature along the two inclined walls. The transient behaviour of an attic space is relevant to our daily life. The instantaneous and non-instantaneous (ramp) heating boundary condition is applied on the sloping walls of the attic space. A theoretical understanding of the transient behaviour of the flow in the enclosure is performed through scaling analysis. A proper identification of the timescales, the velocity and the thickness relevant to the flow that develops inside the cavity makes it possible to predict theoretically the basic flow features that will survive once the thermal flow in the enclosure reaches a steady state. A time scale for the heating-up of the whole cavity together with the heat transfer scales through the inclined walls has also been obtained through scaling analysis. All scales are verified by the numerical simulations.

Natural convection in attics subject to instantaneous and ramp cooling boundary conditions

A fundamental study of the fluid dynamics inside an attic shaped triangular enclosure with cold upper walls and adiabatic horizontal bottom wall is reported in this study. The transient behaviour of the attic fluid which is relevant to our daily life is examined based on a scaling analysis. The transient phenomenon begins with the instantaneous cooling and the cooling with linear decreases of temperature up to some specific time (ramp time) and then maintain constant of the upper sloped walls. It is shown that both inclined walls develop a thermal boundary layer whose thicknesses increase towards steady-state or quasi-steady values. A proper identification of the timescales, the velocity and the thickness relevant to the flow that develops inside the cavity makes it possible to predict theoretically the basic flow features that will survive once the thermal flow in the enclosure reaches a steady state. A time scale for the cooling-down of the whole cavity together with the heat transfer scales through the inclined walls has also been obtained through scaling analysis. All scales are verified by the numerical simulations.

Natural convection and heat transfer in attics subject to periodic thermal forcing

The heat transfer through the attics of buildings under realistic thermal forcing has been considered in this study. A periodic temperature boundary condition is applied on the sloping walls of the attic to show the basic flow features in the attic space over diurnal cycles. The numerical results reveal that, during the daytime heating stage, the flow in the attic space is stratified; whereas at the night-time cooling stage, the flow becomes unstable. A symmetrical solution is seen for relatively low Rayleigh numbers. However, as the Ra gradually increases, a transition occurs at a critical value of Ra. Above this critical value, an asymmetrical solution exhibiting a pitchfork bifurcation arises at the night-time. It is also found that the calculated heat transfer rate at the night-time cooling stage is much higher than that during the daytime heating stage.