Introduction to Abstractionism

First paragraph: Abstractionism in philosophy of mathematics has its origins in Gottlob Frege’s logicism—a position Frege developed in the late nineteenth and early twentieth century. Frege’s main aim was to reduce arithmetic and analysis to logic in order to provide a secure foundation for mathematical knowledge. As is well known, Frege’s development of logicism failed. The infamous Basic Law V— one of the six basic laws of logic Frege proposed in his magnum opus Grundgesetze der Arithmetik—is subject to Russell’s Paradox. The striking feature of Frege’s Basic Law V is that it takes the form of an abstraction principle

Cantor on Frege's Foundations of Arithmetic: Cantor's 1885 Review of Frege's Die Grundlagen der Arithmetik

In 1885, Georg Cantor published his review of Gottlob Frege's Grundlagen der Arithmetik. In this essay, we provide its first English translation together with an introductory note. We also provide a translation of a note by Ernst Zermelo on Cantor's review, and a new translation of Frege's brief response to Cantor. In recent years, it has become philosophical folklore that Cantor's 1885 review of Frege's Grundlagen already contained a warning to Frege. This warning is said to concern the defectiveness of Frege's notion of extension. The exact scope of such speculations varies and sometimes extends as far as crediting Cantor with an early hunch of the paradoxical nature of Frege's notion of extension. William Tait goes even further and deems Frege 'reckless' for having missed Cantor's explicit warning regarding the notion of extension. As such, Cantor's purported inkling would have predated the discovery of the Russell-Zermelo paradox by almost two decades. In our introductory essay, we discuss this alleged implicit (or even explicit) warning, separating two issues: first, whether the most natural reading of Cantor's criticism provides an indication that the notion of extension is defective; second, whether there are other ways of understanding Cantor that support such an interpretation and can serve as a precisification of Cantor's presumed warning

The Convenience of the Typesetter; Notation and Typography in Frege’s Grundgesetze der Arithmetik

We discuss the typography of the notation used by Gottlob Frege in his Grundgesetze der Arithmetik

Overcome procrastination: Enhancing emotion regulation skills reduce procrastination

AbstractProcrastination is a widespread phenomenon that affects performance in various life domains including academic performance. Recently, it has been argued that procrastination can be conceptualized as a dysfunctional response to undesired affective states. Thus, we aimed to test the hypothesis that the availability of adaptive emotion regulation (ER) skills prevents procrastination.In a first study, cross-sectional analyses indicated that ER skills and procrastination were associated and that these connections were mediated by the ability to tolerate aversive emotions. In a second study, cross lagged panel analyses showed that (1) the ability to modify aversive emotions reduced subsequent procrastination and that (2) procrastination affected the subsequent ability to tolerate aversive emotions. Finally, in a third study, a two-arm randomized control trial (RCT) was conducted. Results indicated that systematic training of the ER skills tolerate and modify aversive emotions reduced procrastination. Thus, in order to overcome procrastination, emotion-focused strategies should be considered

Luteolin triggers global changes in the microglial transcriptome leading to a unique anti-inflammatory and neuroprotective phenotype

<p>Abstract</p> <p>Background</p> <p>Luteolin, a plant derived flavonoid, exerts a variety of pharmacological activities and anti-oxidant properties associated with its capacity to scavenge oxygen and nitrogen species. Luteolin also shows potent anti-inflammatory activities by inhibiting nuclear factor kappa B (NFkB) signaling in immune cells. To better understand the immuno-modulatory effects of this important flavonoid, we performed a genome-wide expression analysis in pro-inflammatory challenged microglia treated with luteolin and conducted a phenotypic and functional characterization.</p> <p>Methods</p> <p>Resting and LPS-activated BV-2 microglia were treated with luteolin in various concentrations and mRNA levels of pro-inflammatory markers were determined. DNA microarray experiments and bioinformatic data mining were performed to capture global transcriptomic changes following luteolin stimulation of microglia. Extensive qRT-PCR analyses were carried out for an independent confirmation of newly identified luteolin-regulated transcripts. The activation state of luteolin-treated microglia was assessed by morphological characterization. Microglia-mediated neurotoxicity was assessed by quantifying secreted nitric oxide levels and apoptosis of 661W photoreceptors cultured in microglia-conditioned medium.</p> <p>Results</p> <p>Luteolin dose-dependently suppressed pro-inflammatory marker expression in LPS-activated microglia and triggered global changes in the microglial transcriptome with more than 50 differentially expressed transcripts. Pro-inflammatory and pro-apoptotic gene expression was effectively blocked by luteolin. In contrast, mRNA levels of genes related to anti-oxidant metabolism, phagocytic uptake, ramification, and chemotaxis were significantly induced. Luteolin treatment had a major effect on microglial morphology leading to ramification of formerly amoeboid cells associated with the formation of long filopodia. When co-incubated with luteolin, LPS-activated microglia showed strongly reduced NO secretion and significantly decreased neurotoxicity on 661W photoreceptor cultures.</p> <p>Conclusions</p> <p>Our findings confirm the inhibitory effects of luteolin on pro-inflammatory cytokine expression in microglia. Moreover, our transcriptomic data suggest that this flavonoid is a potent modulator of microglial activation and affects several signaling pathways leading to a unique phenotype with anti-inflammatory, anti-oxidative, and neuroprotective characteristics. With the identification of several novel luteolin-regulated genes, our findings provide a molecular basis to understand the versatile effects of luteolin on microglial homeostasis. The data also suggest that luteolin could be a promising candidate to develop immuno-modulatory and neuroprotective therapies for the treatment of neurodegenerative disorders.</p

Does SMS-Support Make a Difference? Effectiveness of a Two-Week Online-Training to Overcome Procrastination. A Randomized Controlled Trial

The primary purpose of this randomized controlled trial (RCT) was to evaluate the efficacy of an unguided, 2-week internet-based training program to overcome procrastination, called ON.TOP. Because adherence is a typical problem among individuals who tend to procrastinate, especially with internet-based interventions, the secondary purpose of the present study was to investigate whether adding SMS support increases subjects’ frequency of engagement in training. In a three-armed RCT (N = 161), the effects of the intervention alone and intervention with daily SMS-support were compared to a waiting list control condition in a sample of students. The primary outcome of interest was procrastination. The secondary outcome of interest was the extent of training behavior. Baseline (T0), immediate post-treatment (T1) and 8-week post-treatment (T2) assessments were conducted. Results indicated that procrastination decreased significantly only with intervention group with daily SMS support, relative to control. Moreover, incorporating SMS support also may enhance extent of training behavior

Core Circadian Clock Genes Regulate Leukemia Stem Cells in AML

Leukemia stem cells (LSCs) have the capacity to self-renew and propagate disease upon serial transplantation in animal models, and elimination of this cell population is required for curative therapies. Here, we describe a series of pooled, in vivo RNAi screens to identify essential transcription factors (TFs) in a murine model of acute myeloid leukemia (AML) with genetically and phenotypically defined LSCs. These screens reveal the heterodimeric, circadian rhythm TFs Clock and Bmal1 as genes required for the growth of AML cells in vitro and in vivo. Disruption of canonical circadian pathway components produces anti-leukemic effects, including impaired proliferation, enhanced myeloid differentiation, and depletion of LSCs. We find that both normal and malignant hematopoietic cells harbor an intact clock with robust circadian oscillations, and genetic knockout models reveal a leukemia-specific dependence on the pathway. Our findings establish a role for the core circadian clock genes in AML.National Institutes of Health (U.S.) (Grant P01 CA066996)National Institutes of Health (U.S.) (Grant R01 HL082945)National Cancer Institute (U.S.) (Grant P30-CA14051

Identification of Driver and Passenger Mutations of FLT3 by High-Throughput DNA Sequence Analysis and Functional Assessment of Candidate Alleles

SummaryMutations in the juxtamembrane and kinase domains of FLT3 are common in AML, but it is not known whether alterations outside these regions contribute to leukemogenesis. We used a high-throughput platform to interrogate the entire FLT3 coding sequence in AML patients without known FLT3 mutations and experimentally tested the consequences of each candidate leukemogenic allele. This approach identified gain-of-function mutations that activated downstream signaling and conferred sensitivity to FLT3 inhibition and alleles that were not associated with kinase activation, including mutations in the catalytic domain. These findings support the concept that acquired mutations in cancer may not contribute to malignant transformation and underscore the importance of functional studies to distinguish “driver” mutations underlying tumorigenesis from biologically neutral “passenger” alterations