Taking the Lab to the Field: Experimental Tests of Alternative Mechanisms to Procure Multiple Contracts

The first part of the paper reports the results from a sequence of laboratory experiments comparing the bidding behavior for multiple contracts in three different sealed bid auction mechanisms; first-price simultaneous, first-price sequential and first-price combinatorial bidding. The design of the experiment is based on experiences from a public procurement auction of road markings in Sweden. Bidders are asymmetric in their cost functions; some exhibit decreasing average costs of winning more than one contract, whereas other bidders have increasing average cost functions. The combinatorial bidding mechanism is demonstrated to be most efficient. The second part of the paper describes how the lab experiment was followed up by a field test of a combinatorial procurement auction of road markings.Multiple units, non-constant costs, asymmetric redemption values, alternative procurement mechanisms

Safety-Critical Systems and Agile Development: A Mapping Study

In the last decades, agile methods had a huge impact on how software is developed. In many cases, this has led to significant benefits, such as quality and speed of software deliveries to customers. However, safety-critical systems have widely been dismissed from benefiting from agile methods. Products that include safety critical aspects are therefore faced with a situation in which the development of safety-critical parts can significantly limit the potential speed-up through agile methods, for the full product, but also in the non-safety critical parts. For such products, the ability to develop safety-critical software in an agile way will generate a competitive advantage. In order to enable future research in this important area, we present in this paper a mapping of the current state of practice based on {a mixed method approach}. Starting from a workshop with experts from six large Swedish product development companies we develop a lens for our analysis. We then present a systematic mapping study on safety-critical systems and agile development through this lens in order to map potential benefits, challenges, and solution candidates for guiding future research.Comment: Accepted at Euromicro Conf. on Software Engineering and Advanced Applications 2018, Prague, Czech Republi

Pay-as-you-speed: Two Field Experiments on Controlling Adverse Selection and Moral Hazard in Traffic Insurance

Around one million people are killed world wide every year in road-traffic accidents. The risks and consequences of accidents increase progressively with speed, which ultimately is determined by the individual driver. The behaviour of the motorist thus affects both her own and other peoples safety. Internalisation of external costs of road transport has hitherto been focused on distance-based taxes or insurance premiums. While these means, as they are designed today, may affect driven distance, they have no influence on driving behaviour. This paper argues that by linking on-board positioning systems to insurance premiums it is possible to reward careful driving and get drivers to self select into different risk categories depending on their compliance to speed limits. We report two economic field experiments that have tested ways to induce car-owners to have technical platforms installed in their vehicle in order to affect the extent of speeding. It is demonstrated that a bonus to remunerate those that have the device installed, tantamount to a lower insurance premium, increases drivers?propensity to accept the technical devices. In a second experiment the size of the bonus is made dependent on the actual frequency of speeding. We find that this is a second way to discipline users to drive at legal speeds.Traffic safety, impure public goods, moral hazard, adverse selection, self selection

The Effects of Increasing the Minimum Wage on Prices: Analyzing the Incidence of Policy Design and Context

We analyze the price pass-through effect of the minimum wage and use the results to provide insight into the competitive structure of low-wage labor markets. Using monthly price series, we find that the pass-through effect is entirely concentrated on the month that the minimum wage change goes into effect, and is much smaller than what the canonical literature has found. We then discuss why our results differ from that literature, noting the impact of series interpolation in generating most of the previous results. We then use the variation in the size of the minimum wage change to evaluate the competitive nature of low-wage labor markets. Finally, we exploit the rich variation in minimum wage policy of the last 10–15 years—including the rise of state and city-level minimum wage changes and the increased use of indexation—to investigate how the extent of price pass-through varies by policy context. This paper contributes to the literature by clarifying our understanding of the dynamics and magnitude of the pass-through effect and enriching the discussion of how different policies may shape the effect that minimum wage hikes have on prices

Role of transforming growth factor beta in ovarian surface epithelium biology and ovarian cancer

Ovarian cancers arise out of the ovarian surface epithelium (OSE), which is the single layer of epithelial cells covering the ovary. These cells go through repeated cycles of proliferation with the growth and rupture of ovarian follicles. One growth factor involved in the regulation of OSE is transforming growth factor beta (TGFbeta). The different isoforms of TGFbeta (TGFbeta1, TGFbeta2 and TGFbeta3) and its receptor are all present in both OSE and the underlying ovarian surface stroma. The levels of the TGFbeta isoforms and receptors are regulated independently of each other in these different ovarian tissues. Observations suggest the existence of multiple autocrine/paracrine TGFbeta signalling loops. TGFbeta acts to inhibit proliferation of normal OSE and early stage ovarian carcinomas. Conversely, in later stage ovarian cancer the inhibitory actions of TGFbeta on epithelial proliferation have been overcome, while TGFbeta is able to promote malignant neoplastic behaviours. The regulation of TGFbeta signalling by ovarian steroid hormones may be one mechanism by which the OSE responds to cyclic changes in the underlying follicles

Bone morphogenetic protein-4 acts as an ovarian follicle survival factor and promotes primordial follicle development

The growth and development of follicles within the ovary are highly dependent on autocrine and paracrine signaling involving growth factors from granulosa cells, theca cells, stromal interstitial cells, and the oocytes. The growth factor bone morphogenetic protein-4 (BMP-4) and its receptor (BMPR-IB) have been detected in ovaries, and a mutation in BMPR-IB has been associated with abnormal ovulation rate. The objective of the current study was to examine the role that BMP-4 plays in the early stages of primordial follicle development. Ovaries from 4-day-old rats were placed into a whole-ovary organ culture system for 2 wk to investigate the effect that treatment with exogenous BMP-4 has on early follicle development. BMP-4-treated ovaries had a significantly higher proportion of developing primary follicles and fewer arrested primordial follicles than did untreated controls. This indicates that BMP-4 promotes primordial follicle development and the primordial-to-primary follicle transition. Ovaries were also treated with neutralizing antibody against BMP-4 to determine effects of removing endogenously produced BMP-4. Interestingly, ovaries treated with BMP-4 antibody were markedly smaller than controls. This was associated with a progressive loss of oocytes and primordial follicles, a progressive increase in cellular apoptosis, and an accompanying loss of normal ovarian tissue morphology over time. Immunocytochemistry localized BMP-4 protein to isolated stromal cell populations, selected stromal cells (i.e., pretheca cells) associated with developing primordial follicles, and the basement membrane of follicles. Ovaries were treated with BMP-4 and RNA collected after organ culture to determine whether BMP-4 signaling affects expression of other growth factors. Kit ligand and basic fibroblast growth factor expression was unchanged, but TGFalpha expression was decreased in whole ovaries. Taken together, these data suggest that BMP-4 plays an important role in promoting the survival and development of primordial follicles in the neonatal ovary

Role of environmentally induced epigenetic transgenerational inheritance in evolutionary biology Unified Evolution Theory

The current evolutionary biology theory primarily involves genetic alterations and random DNA sequence mutations to generate the phenotypic variation required for Darwinian natural selection to act. This neo-Darwinian evolution is termed the Modern Evolution Synthesis and has been the primary paradigm for nearly 100 years. Although environmental factors have a role in neo-Darwinian natural selection, Modern Evolution Synthesis does not consider environment to impact the basic molecular processes involved in evolution. An Extended Evolutionary Synthesis has recently developed that extends the modern synthesis to consider non-genetic processes. Over the past few decades, environmental epigenetics research has been demonstrated to regulate genetic processes and directly generate phenotypic variation independent of genetic sequence alterations. Therefore, the environment can on a molecular level through non-genetic (i.e. epigenetic) mechanisms directly influence phenotypic variation, genetic variation, inheritance and adaptation. This direct action of the environment to alter phenotype that is heritable is a neo-Lamarckian concept that can facilitate neo-Darwinian (i.e. Modern Synthesis) evolution. The integration of genetics, epigenetics, Darwinian theory, Lamarckian concepts, environment, and epigenetic inheritance provides a paradigm shift in evolution theory. The role of environmental-induced epigenetic transgenerational inheritance in evolution is presented to describe a more unified theory of evolutionary biology

Epigenetics and transgenerational inheritance in domesticated farm animals

Epigenetics provides a molecular mechanism of inheritance that is not solely dependent on DNA sequence and that can account for non-Mendelian inheritance patterns. Epigenetic changes underlie many normal developmental processes, and can lead to disease development as well. While epigenetic effects have been studied in well-characterized rodent models, less research has been done using agriculturally important domestic animal species. This review will present the results of current epigenetic research using farm animal models (cattle, pigs, sheep and chickens). Much of the work has focused on the epigenetic effects that environmental exposures to toxicants, nutrients and infectious agents has on either the exposed animals themselves or on their direct offspring. Only one porcine study examined epigenetic transgenerational effects; namely the effect diet micronutrients fed to male pigs has on liver DNA methylation and muscle mass in grand-offspring (F2 generation). Healthy viable offspring are very important in the farm and husbandry industry and epigenetic differences can be associated with production traits. Therefore further epigenetic research into domestic animal health and how exposure to toxicants or nutritional changes affects future generations is imperative

Post-traumatic osteoarthritis in mice following mechanical injury to the synovial joint

We investigated the spectrum of lesions characteristic of post-traumatic osteoarthritis (PTOA) across the knee joint in response to mechanical injury. We hypothesized that alteration in knee joint stability in mice reproduces molecular and structural features of PTOA that would suggest potential therapeutic targets in humans. The right knees of eight-week old male mice from two recombinant inbred lines (LGXSM-6 and LGXSM-33) were subjected to axial tibial compression. Three separate loading magnitudes were applied: 6N, 9N, and 12N. Left knees served as non-loaded controls. Mice were sacrificed at 5, 9, 14, 28, and 56 days post-loading and whole knee joint changes were assessed by histology, immunostaining, micro-CT, and magnetic resonance imaging. We observed that tibial compression disrupted joint stability by rupturing the anterior cruciate ligament (except for 6N) and instigated a cascade of temporal and topographical features of PTOA. These features included cartilage extracellular matrix loss without proteoglycan replacement, chondrocyte apoptosis at day 5, synovitis present at day 14, osteophytes, ectopic calcification, and meniscus pathology. These findings provide a plausible model and a whole-joint approach for how joint injury in humans leads to PTOA. Chondrocyte apoptosis, synovitis, and ectopic calcification appear to be targets for potential therapeutic intervention

Preterm birth buccal cell epigenetic biomarkers to facilitate preventative medicine

Preterm birth is the major cause of newborn and infant mortality affecting nearly one in every ten live births. The current study was designed to develop an epigenetic biomarker for susceptibility of preterm birth using buccal cells from the mother, father, and child (triads). An epigenome-wide association study (EWAS) was used to identify differential DNA methylation regions (DMRs) using a comparison of control term birth versus preterm birth triads. Epigenetic DMR associations with preterm birth were identified for both the mother and father that were distinct and suggest potential epigenetic contributions from both parents. The mother (165 DMRs) and female child (136 DMRs) at p < 1e-04 had the highest number of DMRs and were highly similar suggesting potential epigenetic inheritance of the epimutations. The male child had negligible DMR associations. The DMR associated genes for each group involve previously identified preterm birth associated genes. Observations identify a potential paternal germline contribution for preterm birth and identify the potential epigenetic inheritance of preterm birth susceptibility for the female child later in life. Although expanded clinical trials and preconception trials are required to optimize the potential epigenetic biomarkers, such epigenetic biomarkers may allow preventative medicine strategies to reduce the incidence of preterm birth