Interactive Genetic Algorithm with Mixed Initiative Interaction for multi-criteria ground water monitoring design

Design of optimal plans for environmental planning and management applications should ideally consider the multiple quantitative and qualitative criteria relevant to the problem. For example, in ground water monitoring design problems, qualitative criteria such as acceptable spatial extent and shape of the contaminant plume predicted from the monitored locations can be equally important as the typical quantitative criteria such as economic costs and contaminant prediction accuracy. Incorporation of qualitative criteria in the problem-solving process is typically done in one of two ways: (a) quantifying approximate representations of the qualitative criteria, which are then used as additional criteria during the optimization process, or (b) post-optimization analysis of designs by experts to evaluate the overall performance of the optimized designs with respect to the qualitative criteria. These approaches, however, may not adequately represent all of the relevant qualitative information that affect a human expert involved in design (e.g. engineers, stakeholders, regulators, etc.), and do not necessarily incorporate the effect of the expert's own learning process on the suitability of the final design. The Interactive Genetic Algorithm with Mixed Initiative Interaction (IGAMII) is a novel approach that addresses these limitations by using a collaborative human-computer search strategy to assist users in designing optimized solutions to their applications, while also learning about their problem. The algorithm adaptively learns from the expert's feedback, and explores multiple designs that meet her/his criteria using both the human expert and a simulated model of the expert's responses in a collaborative fashion. The algorithm provides an introspection-based learning framework for the human expert and uses the human's subjective confidence measures to adjust the optimization search process to the transient learning process of the user. This paper presents the design and testing of this computational framework, and the benefits of using this approach for solving groundwater monitoring design problems.     

Steel-to-concrete bond after concrete splitting: test results

The definite trend towards the use of large-diameter rebars and the introduction of high-strength steels (f _y=500 to 600 MPa) make it necessary to study the effects of longitudinal splitting on the steel-to-concrete bond. The study of splitting effects requires firstly basic tests to be performed in order to gather experimental information on bond and confinement stresses acting at the bar-to-concrete interface. For this purpose, three series of tests were recently carried out at the Politecnico di Milano. The results make it possible to ascertain a few basic properties of the bond after concrete splitting, and to formulate empirical constitutive laws regarding the stresses and the displacements (bar slip and opening of the splitting crack). All specimens consisted of a short deformed bar embedded in a concrete block, which had a preformed splitting crack in the plane passing through the bar axis: twelve specimens (Tests A and C) were fitted up with a round deformed bar having crescent-shaped lugs (D_b=18 mm); seven specimens (Tests B) were fitted up with a specially machined deformed bar having a rectangular cross-section and straigth, lugs, so that concrete deterioration close to the bar could be investigated at the surface of the specimen, by means of the moiré technique. The tests were carried out at constant slip rate, up to very large slip values ( ); both the ascending and the descending branches of the stress-slip curves were measured, for four different values of the opening of the splitting crack. The agreement among the results of the three series is generally satisfactory and often very good: consequently, constitutive laws regarding the four main variables (crack opening and bar slip, shear and confinement stresses) can be worked out, as will be shown in a companion paper on constitutive relationships and on concrete deterioration at the bar-to-concrete interface.     

The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors—A Review of Literature

Hypoxia is an integral component of the tumor microenvironment. Either as chronic or cycling hypoxia, it exerts a similar effect on cancer processes by activating hypoxia-inducible factor-1 (HIF-1) and nuclear factor (NF-κB), with cycling hypoxia showing a stronger proinflammatory influence. One of the systems affected by hypoxia is the CXC chemokine system. This paper reviews all available information on hypoxia-induced changes in the expression of all CXC chemokines (CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8 (IL-8), CXCL9, CXCL10, CXCL11, CXCL12 (SDF-1), CXCL13, CXCL14, CXCL15, CXCL16, CXCL17) as well as CXC chemokine receptors—CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, CXCR7 and CXCR8. First, we present basic information on the effect of these chemoattractant cytokines on cancer processes. We then discuss the effect of hypoxia-induced changes on CXC chemokine expression on the angiogenesis, lymphangiogenesis and recruitment of various cells to the tumor niche, including myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), regulatory T cells (T_regs) and tumor-infiltrating lymphocytes (TILs). Finally, the review summarizes data on the use of drugs targeting the CXC chemokine system in cancer therapies.     

Exosomal Cargo May Hold the Key to Improving Reproductive Outcomes in Dairy Cows

The reproductive status of dairy cows remains a challenge for dairy farmers worldwide, with impaired fertility linked to a significant reduction in herd profitability, due in part to impaired immunity, increased metabolic pressure, and longer postpartum anestrous interval (PPAI). Exosomes are nanovesicles released from a variety of cell types and end up in circulation, and carry proteins, bioactive peptides, lipids, and nucleic acids specific to the place of origin. As such, their role in health and disease has been investigated in humans and animals. This review discusses research into exosomes in the context of reproduction in dairy herds and introduces recent advances in mass-spectrometry (MS) based proteomics that have a potential to advance quantitative profiling of exosomal protein cargo in a search for early biomarkers of cattle fertility.     

Auxin and Root Gravitropism: Addressing Basic Cellular Processes by Exploiting a Defined Growth Response

Root architecture and growth are decisive for crop performance and yield, and thus a highly topical research field in plant sciences. The root system of the model plant Arabidopsis thaliana is the ideal system to obtain insights into fundamental key parameters and molecular players involved in underlying regulatory circuits of root growth, particularly in responses to environmental stimuli. Root gravitropism, directional growth along the gravity, in particular represents a highly sensitive readout, suitable to study adjustments in polar auxin transport and to identify molecular determinants involved. This review strives to summarize and give an overview into the function of PIN-FORMED auxin transport proteins, emphasizing on their sorting and polarity control. As there already is an abundance of information, the focus lies in integrating this wealth of information on mechanisms and pathways. This overview of a highly dynamic and complex field highlights recent developments in understanding the role of auxin in higher plants. Specifically, it exemplifies, how analysis of a single, defined growth response contributes to our understanding of basic cellular processes in general.     

Out-of-Field Hippocampus from Partial-Body Irradiated Mice Displays Changes in Multi-Omics Profile and Defects in Neurogenesis

The brain undergoes ionizing radiation exposure in many clinical situations, particularly during radiotherapy for brain tumors. The critical role of the hippocampus in the pathogenesis of radiation-induced neurocognitive dysfunction is well recognized. The goal of this study is to test the potential contribution of non-targeted effects in the detrimental response of the hippocampus to irradiation and to elucidate the mechanisms involved. C57Bl/6 mice were whole body (WBI) or partial body (PBI) irradiated with 0.1 or 2.0 Gy of X-rays or sham irradiated. PBI consisted of the exposure of the lower third of the mouse body, whilst the upper two thirds were shielded. Hippocampi were collected 15 days or 6 months post-irradiation and a multi-omics approach was adopted to assess the molecular changes in non-coding RNAs, proteins and metabolic levels, as well as histological changes in the rate of hippocampal neurogenesis. Notably, at 2.0 Gy the pattern of early molecular and histopathological changes induced in the hippocampus at 15 days following PBI were similar in quality and quantity to the effects induced by WBI, thus providing a proof of principle of the existence of out-of-target radiation response in the hippocampus of conventional mice. We detected major alterations in DAG/IP3 and TGF-β signaling pathways as well as in the expression of proteins involved in the regulation of long-term neuronal synaptic plasticity and synapse organization, coupled with defects in neural stem cells self-renewal in the hippocampal dentate gyrus. However, compared to the persistence of the WBI effects, most of the PBI effects were only transient and tended to decrease at 6 months post-irradiation, indicating important mechanistic difference. On the contrary, at low dose we identified a progressive accumulation of molecular defects that tended to manifest at later post-irradiation times. These data, indicating that both targeted and non-targeted radiation effects might contribute to the pathogenesis of hippocampal radiation-damage, have general implications for human health.     

Exploring the Biomaterial-Induced Secretome: Physical Bone Substitute Characteristics Influence the Cytokine Expression of Macrophages

In addition to their chemical composition various physical properties of synthetic bone substitute materials have been shown to influence their regenerative potential and to influence the expression of cytokines produced by monocytes, the key cell-type responsible for tissue reaction to biomaterials in vivo. In the present study both the regenerative potential and the inflammatory response to five bone substitute materials all based on β-tricalcium phosphate (β-TCP), but which differed in their physical characteristics (i.e., granule size, granule shape and porosity) were analyzed for their effects on monocyte cytokine expression. To determine the effects of the physical characteristics of the different materials, the proliferation of primary human osteoblasts growing on the materials was analyzed. To determine the immunogenic effects of the different materials on human peripheral blood monocytes, cells cultured on the materials were evaluated for the expression of 14 pro- and anti-inflammatory cytokines, i.e., IL-6, IL-10, IL-1β, VEGF, RANTES, IL-12p40, I-CAM, IL-4, V-CAM, TNF-α, GM-CSF, MIP-1α, Il-8 and MCP-1 using a Bio-Plex^® Multiplex System. The granular shape of bone substitutes showed a significant influence on the osteoblast proliferation. Moreover, smaller pore sizes, round granular shape and larger granule size increased the expression of GM-CSF, RANTES, IL-10 and IL-12 by monocytes, while polygonal shape and the larger pore sizes increased the expression of V-CAM. The physical characteristics of a bone biomaterial can influence the proliferation rate of osteoblasts and has an influence on the cytokine gene expression of monocytes in vitro. These results indicate that the physical structure of a biomaterial has a significant effect of how cells interact with the material. Thus, specific characteristics of a material may strongly affect the regenerative potential in vivo.