The turn of the valve: representing with material models

Many scientific models are representations. Building on Goodman and Elgin’s notion of representation-as we analyse what this claim involves by providing a general definition of what makes something a scientific model, and formulating a novel account of how they represent. We call the result the DEKI account of representation, which offers a complex kind of representation involving an interplay of, denotation, exemplification, keying up of properties, and imputation. Throughout we focus on material models, and we illustrate our claims with the Phillips-Newlyn machine. In the conclusion we suggest that, mutatis mutandis, the DEKI account can be carried over to other kinds of models, notably fictional and mathematical models

Democratization and the Diffusion of Shari'a Law: Comparative Insights from Indonesia

The democratization of politics has been accompanied by a rise of Islamic laws in many Muslim-majority countries. Despite a growing interest in the phenomenon, the Islamization of politics in democratizing Muslim-majority countries is rarely understood as a process that unfolds across space and time. Based on an original dataset established during years of field research in Indonesia, this article analyzes the spread of shari’a regulations across the world’s largest Muslim-majority democracy since 1998. The article shows that shari’a regulations in Indonesia diffused unevenly across space and time. Explanations put forward in the literature on the diffusion of morality policies in other countries such as geographic proximity, institutions, intergovernmental relations and economic conditions did not explain the patterns in the diffusion of shari’a regulations in Indonesia well. Instead, shari’a regulations in Indonesia were most likely to spread across jurisdictions where local Islamist groups situated outside the party system had an established presence. In short, the Islamization of politics was highly contingent on local conditions. Future research will need to pay more attention to local Islamist activists and networks situated outside formal politics as potential causes for the diffusion of shari’a law in democratizing Muslim-majority countries

Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay

The decay channel $\psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p})$ is studied using a sample of $1.06\times 10^8$ $\psi^\prime$ events collected by the BESIII experiment at BEPCII. A strong enhancement at threshold is observed in the $p\bar{p}$ invariant mass spectrum. The enhancement can be fit with an $S$-wave Breit-Wigner resonance function with a resulting peak mass of $M=1861^{+6}_{-13} {\rm (stat)}^{+7}_{-26} {\rm (syst)} {\rm MeV/}c^2$ and a narrow width that is $\Gamma<38 {\rm MeV/}c^2$ at the 90% confidence level. These results are consistent with published BESII results. These mass and width values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics

Computational Analysis of mRNA Expression Profiles Identifies MicroRNA-29a/c as Predictor of Colorectal Cancer Early Recurrence

Colorectal cancer (CRC) is one of the leading malignant cancers with a rapid increase in incidence and mortality. The recurrences of CRC after curative resection are sometimes unavoidable and often take place within the first year after surgery. MicroRNAs may serve as biomarkers to predict early recurrence of CRC, but identifying them from over 1,400 known human microRNAs is challenging and costly. An alternative approach is to analyze existing expression data of messenger RNAs (mRNAs) because generally speaking the expression levels of microRNAs and their target mRNAs are inversely correlated. In this study, we extracted six mRNA expression data of CRC in four studies (GSE12032, GSE17538, GSE4526 and GSE17181) from the gene expression omnibus (GEO). We inferred microRNA expression profiles and performed computational analysis to identify microRNAs associated with CRC recurrence using the IMRE method based on the MicroCosm database that includes 568,071 microRNA-target connections between 711 microRNAs and 20,884 gene targets. Two microRNAs, miR-29a and miR-29c, were disclosed and further meta-analysis of the six mRNA expression datasets showed that these two microRNAs were highly significant based on the Fisher p-value combination (p = 9.14×10−9 for miR-29a and p = 1.14×10−6 for miR-29c). Furthermore, these two microRNAs were experimentally tested in 78 human CRC samples to validate their effect on early recurrence. Our empirical results showed that the two microRNAs were significantly down-regulated (p = 0.007 for miR-29a and p = 0.007 for miR-29c) in the early-recurrence patients. This study shows the feasibility of using mRNA profiles to indicate microRNAs. We also shows miR-29a/c could be potential biomarkers for CRC early recurrence

Comparative Analysis of Human Protein-Coding and Noncoding RNAs between Brain and 10 Mixed Cell Lines by RNA-Seq

In their expression process, different genes can generate diverse functional products, including various protein-coding or noncoding RNAs. Here, we investigated the protein-coding capacities and the expression levels of their isoforms for human known genes, the conservation and disease association of long noncoding RNAs (ncRNAs) with two transcriptome sequencing datasets from human brain tissues and 10 mixed cell lines. Comparative analysis revealed that about two-thirds of the genes expressed between brain and cell lines are the same, but less than one-third of their isoforms are identical. Besides those genes specially expressed in brain and cell lines, about 66% of genes expressed in common encoded different isoforms. Moreover, most genes dominantly expressed one isoform and some genes only generated protein-coding (or noncoding) RNAs in one sample but not in another. We found 282 human genes could encode both protein-coding and noncoding RNAs through alternative splicing in the two samples. We also identified more than 1,000 long ncRNAs, and most of those long ncRNAs contain conserved elements across either 46 vertebrates or 33 placental mammals or 10 primates. Further analysis showed that some long ncRNAs differentially expressed in human breast cancer or lung cancer, several of those differentially expressed long ncRNAs were validated by RT-PCR. In addition, those validated differentially expressed long ncRNAs were found significantly correlated with certain breast cancer or lung cancer related genes, indicating the important biological relevance between long ncRNAs and human cancers. Our findings reveal that the differences of gene expression profile between samples mainly result from the expressed gene isoforms, and highlight the importance of studying genes at the isoform level for completely illustrating the intricate transcriptome

Evidence and morality in harm-reduction debates: can we use value-neutral arguments to achieve value-driven goals?

It is common to argue that politicians make selective use of evidence to tacitly reinforce their moral positions, but all stakeholders combine facts and values to produce and use research for policy. The drug policy debate has largely been framed in terms of an opposition between evidence and politics. Focusing on harm reduction provides useful ground to discuss a further opposition proposed by evidence advocates, that between evidence and morality. Can evidence sway individuals from their existing moral positions, so as to “neutralise” morality? And if not, then should evidence advocates change the way in which they frame their arguments? To address these questions, analysis of N=27 interviews with stakeholders involved in drug policy and harm reduction research, advocacy, lobbying, implementation and decision-making in England, UK and New South Wales, Australia, was conducted. Participants’ accounts suggest that although evidence can help focus discussions away from values and principles, exposure to evidence does not necessarily change deeply held views. Whether stakeholders decide to go with the evidence or not seems contingent on whether they embrace a view of evidence as secular faith; a view that is shaped by experience, politics, training, and role. And yet, morality, values, and emotions underpin all stakeholders’ views, motivating their commitment to drug policy and harm reduction. Evidence advocates might thus benefit from morally and emotionally engaging audiences. This paper aims to develop better tools for analysing the role of morality in decision-making, starting with moral foundations theory. Using tools from disciplines such as moral psychology is relevant to the study of the politics of evidence-based policymaking

Chronic p53-independent p21 expression causes genomic instability by deregulating replication licensing

The cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21) is a cell-cycle checkpoint effector and inducer of senescence, regulated by p53. Yet, evidence suggests that p21 could also be oncogenic, through a mechanism that has so far remained obscure. We report that a subset of atypical cancerous cells strongly expressing p21 showed proliferation features. This occurred predominantly in p53-mutant human cancers, suggesting p53-independent upregulation of p21 selectively in more aggressive tumour cells. Multifaceted phenotypic and genomic analyses of p21-inducible, p53-null, cancerous and near-normal cellular models showed that after an initial senescence-like phase, a subpopulation of p21-expressing proliferating cells emerged, featuring increased genomic instability, aggressiveness and chemoresistance. Mechanistically, sustained p21 accumulation inhibited mainly the CRL4–CDT2 ubiquitin ligase, leading to deregulated origin licensing and replication stress. Collectively, our data reveal the tumour-promoting ability of p21 through deregulation of DNA replication licensing machinery—an unorthodox role to be considered in cancer treatment, since p21 responds to various stimuli including some chemotherapy drugs

Search for Gravitational Waves from Intermediate Mass Binary Black Holes

We present the results of a weakly modeled burst search for gravitational waves from mergers of non-spinning intermediate mass black holes (IMBH) in the total mass range 100--450 solar masses and with the component mass ratios between 1:1 and 4:1. The search was conducted on data collected by the LIGO and Virgo detectors between November of 2005 and October of 2007. No plausible signals were observed by the search which constrains the astrophysical rates of the IMBH mergers as a function of the component masses. In the most efficiently detected bin centered on 88+88 solar masses, for non-spinning sources, the rate density upper limit is 0.13 per Mpc^3 per Myr at the 90% confidence level.Comment: 13 pages, 4 figures: data for plots and archived public version at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=62326, see also the public announcement at http://www.ligo.org/science/Publication-S5IMBH

The role of morphine in regulation of cancer cell growth

Morphine is considered the “gold standard” for relieving pain and is currently one of the most effective drugs available clinically for the management of severe pain associated with cancer. In addition to its use in the treatment of pain, morphine appears to be important in the regulation of neoplastic tissue. Although morphine acts directly on the central nervous system to relieve pain, its activities on peripheral tissues are responsible for many of the secondary complications. Therefore, understanding the impact, other than pain control, of morphine on cancer treatment is extremely important. The effect of morphine on tumor growth is still contradictory, as both growth-promoting and growth-inhibiting effects have been observed. Accumulating evidence suggests that morphine can affect proliferation and migration of tumor cells as well as angiogenesis. Various signaling pathways have been suggested to be involved in these extra-analgesic effects of morphine. Suppression of immune system by morphine is an additional complication. This review provides an update on the influence of morphine on the growth and migration potential of tumor cells