Editorial : Learning, teaching and disseminating knowledge in business process management

Process-oriented thinking has become the major paradigm for managing companies and other organizations. The push for better processes has been even more intense due to rapidly evolving client needs, borderless global markets and innovations swiftly penetrating the market. Thus, education is decisive for successfully introducing and implementing Business Process Management (BPM) initiatives. However, BPM education has been an area of challenge. This special issue aims to provide current research on various aspects of BPM education. It is an initial effort for consolidating better practices, experiences and pedagogical outcomes founded with empirical evidence to contribute towards the three pillars of education: learning, teaching, and disseminating knowledge in BPM.

BoP and MNCs: where is the market and where the source of innovation?

ln 2004 Prahalad made managers aware of the great economic opportunity that the population at the BoP (Base of the Pyramid) could represent for business in the tom of new potential consumers. However, MNCs (Multi-National Corporations) have continued to fail in penetrating low income markets, arguably because applied strategies are often the same adopted at the top of the pyramid. Even in those few cases where products get re-envisioned, theie introduction in contexts of extreme poverty only induces new needs and develops new dependencies. At best the rearrangement of business models by MNCs has meant the realization of CSR (Corporate Social Responsibly) schemes that have validity from a marketing perspective, but still lack the crucial element of social embeddedness (London & Hart, 2004). Today the challenge is lo reach the lowest population tier with reinvented business models based on principles of value co-creation. Starting from a view of the potential consumer at the BoP as a ring of continuity in the value chain process – a resource that can itself produce value - this paper concludes proposing an alternative innovative approach to operate in developing markets that overturns the roles of MNCs and the BoP. The proposed perspective of ‘reversed' source of innovation and primary target market builds on two fundamental tenets: traditional knowledge is rich and greatly unexploded, and markets at the lop of the pyramid are saturated with unnecessary products / practices that have lost contact with the natural environment.

BoP and MNCs: where is the market and where the source of innovation?

ln 2004 Prahalad made managers aware of the great economic opportunity that the population at the BoP (Base of the Pyramid) could represent for business in the tom of new potential consumers. However, MNCs (Multi-National Corporations) have continued to fail in penetrating low income markets, arguably because applied strategies are often the same adopted at the top of the pyramid. Even in those few cases where products get re-envisioned, theie introduction in contexts of extreme poverty only induces new needs and develops new dependencies. At best the rearrangement of business models by MNCs has meant the realization of CSR (Corporate Social Responsibly) schemes that have validity from a marketing perspective, but still lack the crucial element of social embeddedness (London & Hart, 2004). Today the challenge is lo reach the lowest population tier with reinvented business models based on principles of value co-creation. Starting from a view of the potential consumer at the BoP as a ring of continuity in the value chain process – a resource that can itself produce value - this paper concludes proposing an alternative innovative approach to operate in developing markets that overturns the roles of MNCs and the BoP. The proposed perspective of ‘reversed' source of innovation and primary target market builds on two fundamental tenets: traditional knowledge is rich and greatly unexploded, and markets at the lop of the pyramid are saturated with unnecessary products / practices that have lost contact with the natural environment.

In vivo confocal microscopy of the ocular surface : from bench to bedside

In vivo confocal microscopy (IVCM) is an emerging technology that provides minimally invasive, high resolution, steady-state assessment of the ocular surface at the cellular level. Several challenges still remain but, at present, IVCM may be considered a promising technique for clinical diagnosis and management. This mini-review summarizes some key findings in IVCM of the ocular surface, focusing on recent and promising attempts to move “from bench to bedside”. IVCM allows prompt diagnosis, disease course follow-up, and management of potentially blinding atypical forms of infectious processes, such as acanthamoeba and fungal keratitis. This technology has improved our knowledge of corneal alterations and some of the processes that affect the visual outcome after lamellar keratoplasty and excimer keratorefractive surgery. In dry eye disease, IVCM has provided new information on the whole-ocular surface morphofunctional unit. It has also improved understanding of pathophysiologic mechanisms and helped in the assessment of prognosis and treatment. IVCM is particularly useful in the study of corneal nerves, enabling description of the morphology, density, and disease- or surgically induced alterations of nerves, particularly the subbasal nerve plexus. In glaucoma, IVCM constitutes an important aid to evaluate filtering blebs, to better understand the conjunctival wound healing process, and to assess corneal changes induced by topical antiglaucoma medications and their preservatives. IVCM has significantly enhanced our understanding of the ocular response to contact lens wear. It has provided new perspectives at a cellular level on a wide range of contact lens complications, revealing findings that were not previously possible to image in the living human eye. The final section of this mini-review provides a focus on advances in confocal microscopy imaging. These include 2D wide-field mapping, 3D reconstruction of the cornea and automated image analysis.

Calibration functions for estimating soil moisture from GPR dielectric constant measurements

Ground-penetrating radar (GPR) is widely used for assessment of soil moisture variability in field soils. Because GPR does not measure soil water content directly, it is common practice to use calibration functions that describe its relationship with the soil dielectric properties and textural parameters. However, the large variety of models complicates the selection of the appropriate function. In this article an overview is presented of the different functions available, including volumetric models, empirical functions, effective medium theories, and frequency-specific functions. Using detailed information presented in summary tables, the choice for which calibration function to use can be guided by the soil variables available to the user, the frequency of the GPR equipment, and the desired level of detail of the output. This article can thus serve as a guide for GPR practitioners to obtain soil moisture values and to estimate soil dielectric properties.

Impact and energy absorption of portable water-filled road safety barrier system fitted with foam

Portable water-filled barriers (PWFBs) are roadside appurtenances that are used to prevent errant vehicles from penetrating into temporary construction zones on roadways. A numerical model of the composite PWFB, consisting of a plastic shell, steel frame, water and foam was developed and validated against results from full scale experimental tests. This model can be extended to larger scale impact cases, specifically ones that include actual vehicle models. The cost-benefit of having a validated numerical model is significant and this allows the road barrier designer to conduct extensive tests via numerical simulations prior to standard impact tests Effects of foam cladding as additional energy absorption material in the PWFB was investigated. Different types of foam were treated and it was found that XPS foam was the most suitable foam type. Results from this study will aid PWFB designers in developing new generation of roadside structures which will provide enhanced road safety.

Effect of joint mechanism on vehicle redirectional capability of water-filled road safety barrier systems

Portable water-filled barriers (PWFBs) are roadside appurtenances that prevent vehicles from penetrating into temporary construction zones on roadways. PWFBs are required to satisfy the strict regulations for vehicle re-direction in tests. However, many of the current PWFBs fail to re-direct the vehicle at high speeds due to the inability of the joints to provide appropriate stiffness. The joint mechanism hence plays a crucial role in the performance of a PWFB system at high speed impacts. This paper investigates the desired features of the joint mechanism in a PWFB system that can re-direct vehicles at high speeds, while limiting the lateral displacement to acceptable limits. A rectangular “wall” representative of a 30 m long barrier system was modeled and a novel method of joining adjacent road barriers was introduced through appropriate pin-joint connections. The impact response of the barrier “wall” and the vehicle was obtained and the results show that a rotational stiffness of 3000 kNm/rad at the joints seems to provide the desired features of the PWFB system to re-direct impacting vehicles and restrict the lateral deflection. These research findings will be useful to safety engineers and road barrier designers in developing a new generation of PWFBs for increased road safety.

The LCC15-MB human breast cancer cell line expresses osteopontin and exhibits an invasive and metastatic phenotype

We have characterized the LCC15-MB cell line which was recently derived from a breast carcinoma metastasis resected from the femur of a 29-year-old woman. LCC15-MB cells are vimentin (VIM) positive, exhibit a stellate morphology in routine cell culture, and form penetrating colonies when embedded in three-dimensional gels of Matrigel or fibrillar collagen. They show high levels of activity in the Boyden chamber chemomigration and chemoinvasion assays, and like other invasive human breast cancer (HBC) cell lines, LCC15-MB cells activate matrix-metalloproteinase-2 in response to treatment with concanavalin A. In addition, these cells are tumorigenic when implanted subcutaneously in nude mice and recolonize bone after arterial injection. Interestingly, both the primary lesion and the bone metastasis from which LCC15-MB were derived, as well as the resultant cell line, abundantly express the bone matrix protein osteopontin (OPN). OPN is also expressed by the highly metastatic MDA-MB-435 cells, but not other invasive or noninvasive HBC cell lines. Expression of OPN is retained in the subcutaneous xenograft and intraosseous metastases of LCC15-MB as detected by immunohistochemistry. Both VIM and OPN expression have been associated with breast cancer invasion and metastasis, and their expression by the LCC15-MB cell line is consistent with its derivation from a highly aggressive breast cancer. These cells provide a useful model for studying molecular mechanisms important for breast cancer metastasis to bone and, in particular, the implication(s) of OPN and VIM expression in this process.

Association of increased basement membrane invasiveness with absence of estrogen receptor and expression of vimentin in human breast cancer cell lines

Lack of estrogen receptor (ER) and presence of vimentin (VIM) associate with poor prognosis in human breast cancer. We have explored the relationships between ER, VIM, and invasiveness in human breast cancer cell lines. In the matrigel outgrowth assay, ER+/VIM- (MCF-7, T47D, ZR-75-1), and ER-/VIM- (MDA-MB-468, SK-Br-3) cell lines were uninvasive, while ER-/VIM+ (BT549, MDA-MB-231, MDA-MB-435, MDA-MB-436, Hs578T) lines formed invasive, penetrating colonies. Similarly, ER-/VIM+ cell lines were significantly more invasive than either the ER+/VIM- or ER-/VIM- cell lines in the Boyden chamber chemoinvasion assay. Invasive activity in nude mice was only seen with ER-/ VIM+ cell lines MDA-MB-231, MDA-MB-435 and MDA-MB-436. Hs578T cells (ER-/VIM+) showed hematogenous dissemination to the lungs in one of five mice, but lacked local invasion. The ER-/VIM+ MCF-7ADR subline was significantly more active than the MCF-7 cells in vitro, but resembled the wild-type MCF-7 parent in in vivo activity. Data from these cell lines suggest that human breast cancer progression results first in the loss of ER, and subsequently in VIM acquisition, the latter being associated with increased metastatic potential through enhanced invasiveness. The MCF-7ADR data provide evidence that this transition can occur in human breast cancer cells. Vimentin expression may provide useful insights into mechanisms of invasion and/or breast cancer cell progression.

Targeting cancer with a lupus autoantibody

Systemic lupus erythematosus (SLE) is distinct among autoimmune diseases because of its association with circulating autoantibodies reactive against host DNA. The precise role that anti-DNA antibodies play in SLE pathophysiology remains to be elucidated, and potential applications of lupus autoantibodies in cancer therapy have not previously been explored. We report the unexpected finding that a cell-penetrating lupus autoantibody, 3E10, has potential as a targeted therapy for DNA repair–deficient malignancies. We find that 3E10 preferentially binds DNA single-strand tails, inhibits key steps in DNA single-strand and double-strand break repair, and sensitizes cultured tumor cells and human tumor xenografts to DNA-damaging therapy, including doxorubicin and radiation. Moreover, we demonstrate that 3E10 alone is synthetically lethal to BRCA2-deficient human cancer cells and selectively sensitizes such cells to low-dose doxorubicin. Our results establish an approach to cancer therapy that we expect will be particularly applicable to BRCA2-related malignancies such as breast, ovarian, and prostate cancers. In addition, our findings raise the possibility that lupus autoantibodies may be partly responsible for the intrinsic deficiencies in DNA repair and the unexpectedly low rates of breast, ovarian, and prostate cancers observed in SLE patients. In summary, this study provides the basis for the potential use of a lupus anti-DNA antibody in cancer therapy and identifies lupus autoantibodies as a potentially rich source of therapeutic agents.

Markers of genetic susceptibility in human environmental hygiene and toxicology : the role of selected CYP, NAT and GST genes

Inherited genetic traits co-determine the susceptibility of an individual to a toxic chemical. Special emphasis has been put on individual responses to environmental and industrial carcinogens, but other chronic diseases are of increasing interest. Polymorphisms of relevant xenobiotic metabolising enzymes may be used as toxicological susceptibility markers. A growing number of genes encoding enzymes involved in biotransformation of toxicants and in cellular defence against toxicant-induced damage to the cells has been identified and cloned, leading to increased knowledge of allelic variants of genes and genetic defects that may result in a differential susceptibility toward environmental toxicants. "Low penetrating" polymorphisms in metabolism genes tend to be much more common in the population than allelic variants of "high penetrating" cancer genes, and are therefore of considerable importance from a public health point of view. Positive associations between cancer and CYP1A1 alleles, in particular the *2C I462V allele, were found for tissues following the aerodigestive tract. Again, in most cases, the effect of the variant CYP1A1 allele becomes apparent or clearer in connection with the GSTM1 null allele. The CYP1B1 codon 432 polymorphism (CYP1B1*3) has been identified as a susceptibility factor in smoking-related head-and-neck squameous cell cancer. The impact of this polymorphic variant of CYP1B1 on cancer risk was also reflected by an association with the frequency of somatic mutations of the p53 gene. Combined genotype analysis of CYP1B1 and the glutathione transferases GSTM1 or GSTT1 has also pointed to interactive effects. Of particular interest for the industrial and environmental field is the isozyme CYP2E1. Several genotypes of this isozyme have been characterised which seem to be associated with different levels of expression of enzyme activity. The acetylator status for NAT2 can be determined by genotyping or by phenotyping. In the pathogenesis of human bladder cancer due to occupational exposure to "classical" aromatic amines (benzidine, 4-aminodiphenyl, 1-naphthylamine) acetylation by NAT2 is regarded as a detoxication step. Interestingly, the underlying European findings of a higher susceptibility of slow acetylators towards aromatic amines are in contrast to findings in Chinese workers occupationally exposed to aromatic amines which points to different mechanisms of susceptibility between European and Chinese populations. Regarding human bladder cancer, the hypothesis has been put forward that genetic polymorphism of GSTM1 might be linked with the occurrence of this tumour type. This supports the hypothesis that exposure to PAH might causally be involved in urothelial cancers. The human polymorphic GST catalysing conjugation of halomethanes, dihalomethanes, ethylene oxide and a number of other industrial compounds could be characterised as a class theta enzyme (GSTT1) by means of molecular biology. "Conjugator" and "non-conjugator" phenotypes are coincident with the presence and absence of the GSTT1 gene. There are wide variations in the frequencies of GSTT1 deletion (GSTT1 *0/0) among different ethnicities. Human phenotyping is facilitated by the GST activity towards methyl bromide or ethylene oxide in erythrocytes which is representative of the metabolic GSTT1 competence of the entire organism. Inter-individual variations in xenobiotic metabolism capacities may be due to polymorphisms of the genes coding for the enzymes themselves or of the genes coding for the receptors or transcription factors which regulate the expression of the enzymes. Also, polymorphisms in several regions of genes may cause altered ligand affinity, transactivation activity or expression levels of the receptor subsequently influencing the expression of the downstream target genes. Studies of individual susceptibility to toxicants and gene-environment interaction are now emerging as an important component of molecular epidemiology.

Hydraulic conductivity fields: Gaussian or not?

Hydraulic conductivity (K) fields are used to parameterize groundwater flow and transport models. Numerical simulations require a detailed representation of the K field, synthesized to interpolate between available data. Several recent studies introduced high-resolution K data (HRK) at the Macro Dispersion Experiment (MADE) site, and used ground-penetrating radar (GPR) to delineate the main structural features of the aquifer. This paper describes a statistical analysis of these data, and the implications for K field modeling in alluvial aquifers. Two striking observations have emerged from this analysis. The first is that a simple fractional difference filter can have a profound effect on data histograms, organizing non-Gaussian ln K data into a coherent distribution. The second is that using GPR facies allows us to reproduce the significantly non-Gaussian shape seen in real HRK data profiles, using a simulated Gaussian ln K field in each facies. This illuminates a current controversy in the literature, between those who favor Gaussian ln K models, and those who observe non-Gaussian ln K fields. Both camps are correct, but at different scales.

Landform characterization using geophysics—Recent advances, applications, and emerging tools

This paper presents an overview of the strengths and limitations of existing and emerging geophysical tools for landform studies. The objectives are to discuss recent technical developments and to provide a review of relevant recent literature, with a focus on propagating field methods with terrestrial applications. For various methods in this category, including ground-penetrating radar (GPR), electrical resistivity (ER), seismics, and electromagnetic (EM) induction, the technical backgrounds are introduced, followed by section on novel developments relevant to landform characterization. For several decades, GPR has been popular for characterization of the shallow subsurface and in particular sedimentary systems. Novel developments in GPR include the use of multi-offset systems to improve signal-to-noise ratios and data collection efficiency, amongst others, and the increased use of 3D data. Multi-electrode ER systems have become popular in recent years as they allow for relatively fast and detailed mapping. Novel developments include time-lapse monitoring of dynamic processes as well as the use of capacitively-coupled systems for fast, non-invasive surveys. EM induction methods are especially popular for fast mapping of spatial variation, but can also be used to obtain information on the vertical variation in subsurface electrical conductivity. In recent years several examples of the use of plane wave EM for characterization of landforms have been published. Seismic methods for landform characterization include seismic reflection and refraction techniques and the use of surface waves. A recent development is the use of passive sensing approaches. The use of multiple geophysical methods, which can benefit from the sensitivity to different subsurface parameters, is becoming more common. Strategies for coupled and joint inversion of complementary datasets will, once more widely available, benefit the geophysical study of landforms.Three cases studies are presented on the use of electrical and GPR methods for characterization of landforms in the range of meters to 100. s of meters in dimension. In a study of polygonal patterned ground in the Saginaw Lowlands, Michigan, USA, electrical resistivity tomography was used to characterize differences in subsurface texture and water content associated with polygon-swale topography. Also, a sand-filled thermokarst feature was identified using electrical resistivity data. The second example is on the use of constant spread traversing (CST) for characterization of large-scale glaciotectonic deformation in the Ludington Ridge, Michigan. Multiple CST surveys parallel to an ~. 60. m high cliff, where broad (~. 100. m) synclines and narrow clay-rich anticlines are visible, illustrated that at least one of the narrow structures extended inland. A third case study discusses internal structures of an eolian dune on a coastal spit in New Zealand. Both 35 and 200. MHz GPR data, which clearly identified a paleosol and internal sedimentary structures of the dune, were used to improve understanding of the development of the dune, which may shed light on paleo-wind directions.

Hydrostratigraphic analysis of the MADE site with full-resolution GPR and direct-push hydraulic profiling

Full-resolution 3D Ground-Penetrating Radar (GPR) data were combined with high-resolution hydraulic conductivity (K) data from vertical Direct-Push (DP) profiles to characterize a portion of the highly heterogeneous MAcro Dispersion Experiment (MADE) site. This is an important first step to better understand the influence of aquifer heterogeneities on observed anomalous transport. Statistical evaluation of DP data indicates non-normal distributions that have much higher similarity within each GPR facies than between facies. The analysis of GPR and DP data provides high-resolution estimates of the 3D geometry of hydrostratigraphic zones, which can then be populated with stochastic K fields. The lack of such estimates has been a significant limitation for testing and parameterizing a range of novel transport theories at sites where the traditional advection-dispersion model has proven inadequate.

4D GPR tracking of water infiltration in fractured high-porosity limestone

Three thousand liters of water were infiltrated from a 4 m diameter pond to track flow and transport inside fractured carbonates with 20-40 % porosity. Sixteen time-lapse 3D Ground Penetrating Radar (GPR) surveys with repetition intervals between 2 hrs and 5 days monitored the spreading of the water bulb in the subsurface. Based on local travel time shifts between repeated GPR survey pairs, localized changes of volumetric water content can be related to the processes of wetting, saturation and drainage. Deformation bands consisting of thin sub vertical sheets of crushed grains reduce the magnitude of water content changes but enhance flow in sheet parallel direction. This causes an earlier break through across a stratigraphic boundary compared to porous limestone without deformation bands. This experiment shows how time-lapse 3D GPR or 4D GPR can non-invasively track ongoing flow processes in rock-volumes of over 100 m3.