MULTI-OBJECTIVE STRATEGY FOR OPTIMIZING REPETITIVE CONSTRUCTION PROJECTS USING LINEAR PROGRAMMING MODELS

Decision making has become much more complicated than in the past due to increased decision alternatives, uncertainty, and cost of making errors. As a result, it is very difficult to rely on a trial and error approach in decision making. Nowadays business managers are dealing with different types of projects ranging from implementing a large scale manufacturing plant to a simple sales campaign. While dealing with projects, to become competitive, sometimes it is required to complete a project within the predetermined deadline to keep cost at lowest possible level. Failure to do so ultimately leads to increase in total cost. This would direct managers to encounter a decision situation: which activities of the project will be crashed to minimize the total cost of crashing project. In this paper, we provide a hypothetical example to clarify the framework of how to convert from LOB to CPM and then how to create a model to crash a project time to reach an optimum time-cost solution. Microsoft Excel custom made sheets used to the conversion, also Solver add-in used to solve the model while it implements Linear Programming. As a check, results from Solver and LiPS software are compared

Geophysical investigations of a geothermal anomaly at Wadi Ghadir, eastern Egypt

During regional heat flow studies a geothermal anomaly was discovered approximately 2 km from the Red Sea coast at Wadi Ghadir, in the Red Sea Hills of Eastern Egypt. A temperature gradient of 55 C/km was measured in a 150 m drillhole at this location, indicating a heat flow of approximately 175 mw/sqm, approximately four times the regional background heat flow for Egypt. Gravity and magnetic data were collected along Wadi Ghadir, and combined with offshore gravity data, to investigate the source of the thermal anomaly. Magnetic anomalies in the profile do not coincide with the thermal anomaly, but were observed to correlate with outcrops of basic rocks. Other regional heat flow and gravity data indicate that the transition from continental to oceanic type lithosphere occurs close to the Red Sea margin, and that the regional thermal anomaly is possibly related to the formation of the Red Sea

Automating Verification of State Machines with Reactive Designs and Isabelle/UTP

State-machine based notations are ubiquitous in the description of component systems, particularly in the robotic domain. To ensure these systems are safe and predictable, formal verification techniques are important, and can be cost-effective if they are both automated and scalable. In this paper, we present a verification approach for a diagrammatic state machine language that utilises theorem proving and a denotational semantics based on Unifying Theories of Programming (UTP). We provide the necessary theory to underpin state machines (including induction theorems for iterative processes), mechanise an action language for states and transitions, and use these to formalise the semantics. We then describe the verification approach, which supports infinite state systems, and exemplify it with a fully automated deadlock-freedom check. The work has been mechanised in our proof tool, Isabelle/UTP, and so also illustrates the use of UTP to build practical verification tools.Comment: 18 pages, 16th Intl. Conf. on Formal Aspects of Component Software (FACS 2018), October 2018, Pohang, South Kore

Involvement of a specificity proteins-binding element in regulation of basal and estrogen-induced transcription activity of the BRCA1 gene

INTRODUCTION:Increased estrogen level has been regarded to be a risk factor for breast cancer. However, estrogen has also been shown to induce the expression of the tumor suppressor gene, BRCA1. Upregulation of BRCA1 is thought to be a feedback mechanism for controlling DNA repair in proliferating cells. Estrogens enhance transcription of target genes by stimulating the association of the estrogen receptor (ER) and related coactivators to estrogen response elements or to transcription complexes formed at activator protein (AP)-1 or specificity protein (Sp)-binding sites. Interestingly, the BRCA1 gene lacks a consensus estrogen response element. We previously reported that estrogen stimulated BRCA1 transcription through the recruitment of a p300/ER-alpha complex to an AP-1 site harbored in the proximal BRCA1 promoter. The purpose of the study was to analyze the contribution of cis-acting sites flanking the AP-1 element to basal and estrogen-dependent regulation of BRCA1 transcription.METHODS:Using transfection studies with wild-type and mutated BRCA1 promoter constructs, electromobility binding and shift assays, and DNA-protein interaction and chromatin immunoprecipitation assays, we investigated the role of Sp-binding sites and cAMP response element (CRE)-binding sites harbored in the proximal BRCA1 promoter.RESULTS:We report that in the BRCA1 promoter the AP-1 site is flanked upstream by an element (5'-GGGGCGGAA-3') that recruits Sp1, Sp3, and Sp4 factors, and downstream by a half CRE-binding motif (5'-CGTAA-3') that binds CRE-binding protein. In ER-alpha-positive MCF-7 cells and ER-alpha-negative Hela cells expressing exogenous ER-alpha, mutation of the Sp-binding site interfered with basal and estrogen-induced BRCA1 transcription. Conversely, mutation of the CRE-binding element reduced basal BRCA1 promoter activity but did not prevent estrogen activation. In combination with the AP-1/CRE sites, the Sp-binding domain enhanced the recruitment of nuclear proteins to the BRCA1 promoter. Finally, we report that the MEK1 (mitogen-activated protein kinase kinase-1) inhibitor PD98059 attenuated the recruitment of Sp1 and phosphorylated ER-alpha, respectively, to the Sp and AP-1 binding element.CONCLUSION:These cumulative findings suggest that the proximal BRCA1 promoter segment comprises cis-acting elements that are targeted by Sp-binding and CRE-binding proteins that contribute to regulation of BRCA1 transcription.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]

The Evolution of Facultative Conformity Based on Similarity

Conformist social learning can have a pronounced impact on the cultural evolution of human societies, and it can shape both the genetic and cultural evolution of human social behavior more broadly. Conformist social learning is beneficial when the social learner and the demonstrators from whom she learns are similar in the sense that the same behavior is optimal for both. Otherwise, the social learner's optimum is likely to be rare among demonstrators, and conformity is costly. The trade-off between these two situations has figured prominently in the longstanding debate about the evolution of conformity, but the importance of the trade-off can depend critically on the flexibility of one's social learning strategy. We developed a gene-culture coevolutionary model that allows cognition to encode and process information about the similarity between naive learners and experienced demonstrators. Facultative social learning strategies that condition on perceived similarity evolve under certain circumstances. When this happens, facultative adjustments are often asymmetric. Asymmetric adjustments mean that the tendency to follow the majority when learners perceive demonstrators as similar is stronger than the tendency to follow the minority when learners perceive demonstrators as different. In an associated incentivized experiment, we found that social learners adjusted how they used social information based on perceived similarity, but adjustments were symmetric. The symmetry of adjustments completely eliminated the commonly assumed trade-off between cases in which learners and demonstrators share an optimum versus cases in which they do not. In a second experiment that maximized the potential for social learners to follow their preferred strategies, a few social learners exhibited an inclination to follow the majority. Most, however, did not respond systematically to social information. Additionally, in the complete absence of information about their similarity to demonstrators, social learners were unwilling to make assumptions about whether they shared an optimum with demonstrators. Instead, social learners simply ignored social information even though this was the only information available. Our results suggest that social cognition equips people to use conformity in a discriminating fashion that moderates the evolutionary trade-offs that would occur if conformist social learning was rigidly applied

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

The genesis of cerebellar interneurons and the prevention of neural DNA damage require XRCC1

Defective responses to DNA single strand breaks underlie various neurodegenerative diseases. However, the exact role of this repair pathway during the development and maintenance of the nervous system is unclear. Using murine neural-specific inactivation of Xrcc1, a factor that is critical for the repair of DNA single strand breaks, we found a profound neuropathology that is characterized by the loss of cerebellar interneurons. This cell loss was linked to p53-dependent cell cycle arrest and occurred as interneuron progenitors commenced differentiation. Loss of Xrcc1 also led to the persistence of DNA strand breaks throughout the nervous system and abnormal hippocampal function. Collectively, these data detail the in vivo link between DNA single strand break repair and neurogenesis and highlight the diverse consequences of specific types of genotoxic stress in the nervous system

Whole organisms or pure compounds? entourage effect versus drug specificity

As the therapeutic use of sacred plants and fungi becomes increasingly accepted by Western medicine, a tug of war has been taking place between those who advocate the traditional consumption of whole organisms and those who defend exclusively the utilization of purified compounds. The attempt to reduce organisms to single active principles is challenged by the sheer complexity of traditional medicine. Ayahuasca, for example, is a concoction of at least two plant species containing multiple psychoactive substances with complex interactions. Similarly, cannabis contains dozens of psychoactive substances whose specific combinations in different strains correspond to different types of therapeutic and cognitive effects. The “entourage effect” refers to the synergistic effects of the multiple compounds present in whole organisms, which may potentiate clinical efficacy while attenuating side effects. In opposition to this view, mainstream pharmacology is adamant about the need to use purified substances, presumably more specific and safe. In this chapter, I will review the evidence on both sides to discuss the scientific, economic, and political implications of this controversy. The evidence indicates that it is time to embrace the therapeutic complexity of psychedelics.2019-07-3