488 research outputs found
Signaling changes in the stem cell factor–AKT-S6 pathway in diagnostic AML samples are associated with disease relapse
The Relationship Between Belief and Credence
Sometimes epistemologists theorize about belief, a tripartite attitude on which one can believe, withhold belief, or disbelieve a proposition. In other cases, epistemologists theorize about credence, a fine-grained attitude that represents one’s subjective probability or confidence level toward a proposition. How do these two attitudes relate to each other? This article explores the relationship between belief and credence in two categories: descriptive and normative. It then explains the broader significance of the belief-credence connection and concludes with general lessons from the debate thus far
Whither Evidentialist Reliabilism?
Evidentialism and Reliabilism are two of the main contemporary theories of epistemic justification. Some authors have thought that the theories are not incompatible with each other, and that a hybrid theory which incorporates elements of both should be taken into account. More recently, other authors have argued that the resulting theory is well- placed to deal with fine-grained doxastic attitudes (credences).
In this paper I review the reasons for adopting this kind of hybrid theory, paying attention to the case of credences and the notion of probability involved in their treatment. I argue that the notion of probability in question can only be an epistemic (or evidential) kind of probability. I conclude that the resulting theory will be incompatible with Reliabilism in one important respect: it cannot deliver on the reductivist promise of Reliabilism. I also argue that attention to the justification of basic beliefs reveals limitations in the Evidentialist framework as well. The theory that results from the right combination of Evidentialism and Reliabilism, therefore, is neither Evidentialist nor Reliabilist
Cyclin D1 and mammary carcinoma: new insights from transgenic mouse models
Cyclin D1 is one of the most commonly overexpressed oncogenes in breast cancer, with 45–50% of primary ductal carcinomas overexpressing this oncoprotein. Targeted deletion of the gene encoding cyclin D1 demonstrates an essential role in normal mammary gland development while transgenic studies provide evidence that cyclin D1 is a weak oncogene in mammary epithelium. In a recent exciting development, Yu et al. demonstrate that cyclin D1-deficient mice are resistant to mammary carcinomas induced by c-neu and v-Ha-ras, but not those induced by c-myc or Wnt-1. These findings define a pivotal role for cyclin D1 in a subset of mammary cancers in mice and imply a functional role for cyclin D1 overexpression in human breast cancer
Bladder neck mobility in continent nulliparous women
To evaluate the mobility of the vesical neck during coughing and valsalva in healthy nulliparous volunteers and to test the reliability of the technique applied. Design Clinical observational study. Setting Department of Obstetrics and Gynaecology, Cantonal Hospital Lucerne, Switzerland. Population Thirty-nine nulliparous volunteers. Methods Vesical neck motion was assessed with perineal ultrasound. Intra–abdominal pressure was controlled for with an intrarectal probe. Intra-rater reliability was evaluated. Results Vesical neck mobility was significantly lower during coughing (8 mm, SD 4 mm) than during valsalva (15 mm, SD 10 mm) ( P < 0.005 ). Between individuals mobility varied from 4 mm to 32 mm during coughing and from 2 mm to 31 mm during valsalva. Test-retest-studies showed a maximum difference between to tests during coughing of 4 mm and during valsalva of 5 mm. Conclusion The bladder neck is mobile in normal continent women and bladder neck mobility is lower during coughing than during Valsalva.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74987/1/j.1471-0528.2001.00066.x.pd
Standing in a Garden of Forking Paths
According to the Path Principle, it is permissible to expand your set of beliefs iff (and because) the evidence you possess provides adequate support for such beliefs. If there is no path from here to there, you cannot add a belief to your belief set. If some thinker with the same type of evidential support has a path that they can take, so do you. The paths exist because of the evidence you possess and the support it provides. Evidential support grounds propositional justification.
The principle is mistaken. There are permissible steps you may take that others may not even if you have the very same evidence. There are permissible steps that you cannot take that others can even if your beliefs receive the same type of evidential support. Because we have to assume almost nothing about the nature of evidential support to establish these results, we should reject evidentialism
GateFinder: projection-based gating strategy optimization for flow and mass cytometry
Motivation: High-parameter single-cell technologies can reveal novel cell populations of interest, but studying or validating these populations using lower-parameter methods remains challenging.Results: Here, we present GateFinder, an algorithm that enriches high-dimensional cell types with simple, stepwise polygon gates requiring only two markers at a time. A series of case studies of complex cell types illustrates how simplified enrichment strategies can enable more efficient assays, reveal novel biomarkers and clarify underlying biology
Coordinate control of cell cycle regulatory genes in zebrafish development tested by cyclin D1 knockdown with morpholino phosphorodiamidates and hydroxyprolyl-phosphono peptide nucleic acids
During early zebrafish (Danio rerio) development zygotic transcription does not begin until the mid-blastula transition (MBT) ∼3 h after fertilization. MBT demarcates transition from synchronous short cell cycles of S and M phases exclusively to full cycles encompassing G(1) and G(2) phases. Transcriptional profiling and RT–PCR analyses during these phases enabled us to determine that this shift corresponds to decreased transcript levels of S/M phase cell cycle control genes (e.g. ccna2, ccnb1, ccnb2 and ccne) and increased transcript levels of ccnd1, encoding cyclin D1, and orthologs of p21 (p21-like) and retinoblastoma (Rb-like 1). To investigate the regulation of this process further, the translation of ccnd1 mRNA, a G(1)/S checkpoint control element, was impaired by microinjection of ccnd1-specific morpholino phosphorodiamidate (MO) 20mer or hydroxyprolyl-phosphono peptide nucleic acid (HypNA-pPNA) 16mer antisense oligonucleotides. The resulting downregulation of cyclin D1 protein resulted in microophthalmia and microcephaly, but not lethality. The phenotypes were not seen with 3-mismatch MO 20mers or 1-mismatch HypNA-pPNA 16mers, and were rescued by an exogenous ccnd1 mRNA construct with five mismatches. Collectively, these results indicate that transcription of key molecular determinants of asynchronous cell cycle control in zebrafish embryos commences at MBT and that the reduction of cyclin D1 expression compromises zebrafish eye and head development
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