Empirical Analysis of Mutation Operator Selection Strategies for Genetic Improvement

Genetic improvement (GI) tools find improved program versions by modifying the initial program. These can be used for the purpose of automated program repair (APR). GI uses software transformations, called mutation operators, such as deletions, insertions, and replacements of code fragments. Current edit selection strategies, however, under-explore the search spaces of insertion and replacement operators. Therefore, we implement a uniform strategy based on the relative operator search space sizes. We evaluate it on the QuixBugs repair benchmark and find that the uniform strategy has the potential for improving APR tool performance. We also analyse the efficacy of the different mutation operators with regard to the type of code fragment they are applied to. We find that, for all operators, choosing expression statements as target statements is the most successful for finding program variants with improved or preserved fitness (50.03%, 33.12% and 23.85% for deletions, insertions and replacements, respectively), whereas choosing declaration statements is the least effective (3.16%, 10.82% and 3.14% for deletions, insertions and replacements)

Argonaute 2 immunoprecipitation revealed large tumor suppressor kinase 1 as a novel proapoptotic target of miR-21 in T cells

MicroRNA (miR)-21 is an important suppressor of T-cell apoptosis that is also overexpressed in many types of cancers. The exact mechanisms underlying the antiapoptotic effects of miR-21 are not well understood. In this study, we used the Jurkat T-cell line as a model to identify apoptosis-associated miR-21 target genes. We showed that expression of miR-21 rapidly increases upon alpha CD3/alpha CD28 activation of Jurkat cells. Inhibition of miR-21 reduced cell growth which could be explained by an increase in apoptosis. MicroRNA target gene identification by AGO2 RNA-immunoprecipitation followed by gene expression microarray (RIP-Chip) resulted in the identification of 72 predicted miR-21 target genes that were at least twofold enriched in the AGO2-IP fraction of miR-21 overexpressing cells. Of these, 71 were at least twofold more enriched in the AGO2-IP fraction of miR-21 overexpressing cells as compared to AGO2-IP fraction of control cells. The target gene for which the AGO2-IP enrichment was most prominently increased upon miR-21 overexpression was the proapoptotic protein LATS1. Luciferase reporter assays and western blot analysis confirmed targeting of LATS1 by miR-21. qRT-PCR analysis in primary T cells showed an inverse expression pattern between LATS1 transcript levels and miR-21 upon T-cell stimulation. Finally, LATS1 knockdown partially rescued the miR-21 inhibition-induced impaired cell growth. Collectively, these data identify LATS1 as a miR-21 target important for the antiapoptotic function of miR-21 in T cells and likely also in many types of cancer

CSR jako źródło konkurencyjności kanałów dystrybucji

Celem artykułu jest wskazanie na udział CSR w budowaniu przewagi konkurencyjnej kanału dystrybucji. Autorki problem ten rozpatrują dla uwarunkowań współczesnej gospodarki, w której nie konkurują między sobą pojedyncze przedsiębiorstwa ale łańcuchy dostaw; również w Polsce daje się obecnie zauważyć postępujący proces przekształcania kanałów dystrybucji w łańcuchy dostaw. Łańcuchy ulegają również skróceniu - coraz częściej hurtownicy są w nich pomijani. W artykule sformułowano tezę, iż uczestnicy kanałów dystrybucji opartych na idei CSR dostarczają wyższą wartość dla finalnego nabywcy. Wartość tworzona w kanale dystrybucji rozumiana jest zgodnie z ujęciem M. Portera, jako wartość ekonomiczno-społeczna. Przedmiotem szczególnej uwagi są nowoczesne kanały dystrybucji na rynku FMCG w Polsce, w których silne kapitałowo przedsiębiorstwa handlowe mają znaczący wpływ na dostawców (producentów) towarów. Artykuł ma charakter teoretyczny, aczkolwiek przytoczono w nim przykłady z praktyki. Rezultatem jest wyjaśnienie mechanizmów zwiększających wartość kanałów dystrybucji działających w oparciu o ideę CSR. Oczekiwany rezultat praktyczny to identyfikacja obszarów, które zachęcałyby detalistów do zacieśniania współpracy w kanałach dystrybucji z dostawcami w oparciu o ideę CSR oraz wskazanie na rozwiązania, jakie można w tym zakresie podejmować.The article aims to indicate CSR's contribution to building the competitive advantage of the distribution channel. The authors examine the problem with regard to the modern economy where the competition is not between individual enterprises but supply channels; also in Poland one can observe a continuing transformation of distribution channels into supply chains. The chains are also shortened - wholesalers are more and more often omitted in the process. The article contains a thesis that participants of distribution channels based on the idea of CSR provide a greater value for the end buyer. The value developed in the distribution channel is understood in accordance with M. Porter's perspective as a socio-economic value. Worth particular attention are modern distribution channels on the FMCG market in Poland, in which economically strong trading companies have a significant influence on suppliers (producers) of goods. The article is theoretical in nature although it includes examples of practice. Its outcome is explanation of mechanisms increasing the value of distribution channels based on the idea of CSR. The expected practical result is identifying areas which would encourage retailers to tighten cooperation with suppliers in distribution channels based on the idea of CSR, and indicating solutions which can be applied for this purpose

Nowe wyzwania dla handlu detalicznego i marketingu - zrównoważona konsumpcja a innowacje przedsiębiorstw handlowych

Sustainable consumption is a term related to the type of consumer behavior being a part of the broader concept of sustainable development. In the process of selecting the method of satisfying their needs, consumers take into account a number of factors which minimize the negative influence of their buying decisions on the natural environment and the society. The goal of the article is to identify consumers aiming at sustainable consumption and to explain the way in which companies respond to these consumers’ needs by means of innovations – particularly that of the marketing and organizational nature. The study focuses on retail companies for a few reasons. First of all, companies of this type have the following characteristics: proximity to consumers, cooperation with producers in creating their offer, as well as shaping sales channels and developing a variety of time and space solutions facilitating the efficient need satisfaction. What is more, they are also leaders in innovation – these are the retail companies that adopted a number of innovations during the economic transformation period. In the last part of the article the companies’ objectives are confronted with the consumers’ aims, as well as barriers to development and factors conducive to sustainable consumption are discussed.Zrównoważona konsumpcja to termin określający pewien rodzaj zachowań konsumenckich, wynikający z szerszej koncepcji – zrównoważonego rozwoju. Konsumenci, wybierając sposób zaspokojenia potrzeby, biorą zarazem pod uwagę szereg czynników, które zapewniają minimalizowanie negatywnych dla środowiska naturalnego i społeczeństwa skutków własnych decyzji zakupowych. W artykule dokonano charakterystyki i identyfikacji konsumentów dążących do zrównoważonej konsumpcji. Ponadto wyjaśniono, w jaki sposób przedsiębiorstwa odpowiadają na potrzeby tych nabywców innowacjami – w szczególności marketingowymi i organizacyjnymi. W opracowaniu skupiono się na przedsiębiorstwach handlowych z kilku powodów. Przede wszystkim przedsiębiorstwa handlowe wyróżniają takie cechy, jak: bliskość względem konsumentów, współtworzenie oferty z producentami, a także kształtowanie kanałów sprzedaży i tworzenie szeregu udogodnień czasowych i przestrzennych umożliwiających sprawne zaspokajanie potrzeb. Są one także wiodącymi podmiotami pod względem innowacji – to właśnie przedsiębiorstwa handlowe najszybciej zaadoptowały szereg innowacji w okresie transformacji gospodarki. W ostatniej części skonfrontowano dążenia przedsiębiorstw z celami konsumentów i wskazano na bariery rozwoju i czynniki sprzyjające zrównoważonej konsumpcji

SF Treg cells transcribing high levels of Bcl-2 and microRNA-21 demonstrate limited apoptosis in RA

Objective. The aim of this study was to investigate the turnover of Treg cells in the SF of RA patients. Methods. Treg cells were enumerated in peripheral blood and SF of RA patients and analysed by flow cytometry for expression of the proliferation marker Ki-67 and binding of the apoptosis marker annexin V. Sorted Treg cells of RA patients were analysed for expression of anti-apoptotic regulators Bcl-2 and microRNA-21 (miR-21) by RT-PCR. Results. Treg cells displaying a memory phenotype were abundant in the SF of RA patients. SF Treg cells more frequently expressed the proliferation marker Ki-67 than conventional T cells. Only few SF Treg cells were apoptotic, as indicated by limited annexin V staining of these cells. SF Treg cells displayed high transcription levels of Bcl-2 and miR-21 in comparison with SF conventional T cells and peripheral blood Treg cells. Conclusion. Treg cells with a memory phenotype accumulate in the SF of RA patients. These Treg cells have a high proliferative activity and demonstrate little apoptosis. The latter finding could be explained by high transcription of Bcl-2 and miR-21 in SF Treg cells

Dissociations in Cortical Morphometry in Youth with Down Syndrome: Evidence for Reduced Surface Area but Increased Thickness

Detailed descriptions of cortical anatomy in youth with Down syndrome (DS), the most common genetic cause of intellectual disability (ID), are scant. Thus, the current study examined deviations in cortical thickness (CT) and surface area (SA), at high spatial resolution, in youth with DS, to identify focal differences relative to typically developing (TD) youth. Participants included 31 youth with DS and 45 age- and sex-matched TD controls (mean age ∼16 years; range = 5–24 years). All participants completed T1-weighted ASSET-calibrated magnetization prepared rapid gradient echo scans on a 3-T magnetic resonance imaging scanner. Replicating prior investigations, cortical volumewas reduced in DS comparedwith controls. However, a novel dissociation for SA and CTwas found—namely, SAwas reduced (predominantly in frontal and temporal regions) while CTwas increased (notably in several regions thought to belong to the default mode network; DMN). These findings suggest that reductions in SA rather thanCTare driving the cortical volume reductions reported in prior investigations of DS.Moreover, given the link betweenDMN functionality andAlzheimer’s symptomatology in chromosomally typical populations, future DS studies may benefit from focusing on the cortex in DMN regions, as such investigations may provide clues to the precocious onset of Alzheimer’s disease in this at-risk group. Key words: Alzheimer’s disease, cerebral cortex, intellectual disability, magnetic resonance imaging, Trisomy 2