Practical grounds for belief: Kant and James on religion

Both Kant and James claim to limit the role of knowledge in order to make room for faith. In this paper, we argue that despite some similarities, their attempts to do this come apart. Our main claim is that, although both Kant and James justify our adopting religious beliefs on practical grounds, James believes that we can—and should—subsequently assess such beliefs on the basis of evidence. We offer our own account of this evidence and discuss what this difference means for their accounts of religious belief

Practical grounds for freedom: Kant and James on freedom, experience and an open future

In this chapter, we compare Kant and James’ accounts of freedom. Despite both thinkers’ rejecting compatibilism for the sake of practical reason, there are two striking differences in their stances. The first concerns whether or not freedom requires the possibility of an open future. James holds that morality hinges on the real possibility that the future can be affected by our actions. Kant, on the other hand, seems to maintain that we can still be free in the crucial sense, even if none of our actions can have any effect on the future. The second difference between them is related, and concerns the location of freedom. Kant views experience as determined by natural necessity, and locates freedom outside of it, in things-in-themselves. James, on the other hand, has a richer conception of experience than Kant, and holds that we can locate our freedom within experience alone. In the end, we contend that James has a better account of how freedom relates to our experience, but this comes at a cost. For while Kant's account struggles with the relationship between freedom and experience, it has the advantage of insulating our freedom from potential empirical challenges

A Semi-Empirical Model of the Infra-Red Universe

We present a simple model of the infra-red universe, based as much as possible on local observations. We model the luminosity and number evolution of disk and starburst galaxies, including the effects of dust, gas and spectral evolution. Although simple, our approach is able to reproduce observations of galaxy number counts and the infra-red and sub-millimeter extra-galactic backgrounds. It provides a useful probe of galaxy formation and evolution out to high redshift. The model demonstrates the significant role of the starburst population and predicts high star formation rates at redshifts 3 to 4, consistent with recent extinction-corrected observations of Lyman break galaxies. Starbursting galaxies are predicted to dominate the current SCUBA surveys. Their star formation is driven predominantly by strong tidal interactions and mergers of galaxies. This leads to the creation of spheroidal stellar systems, which may act as the seeds for disk formation as gas infalls. We predict the present-day baryonic mass in bulges and halos is comparable to that in disks. From observations of the extra-galactic background, the model predicts that the vast majority of star formation in the Universe occurs at z<5.Comment: 23 pages including 9 figures. To appear in ApJ. Model results available electronically at http://astro.berkeley.edu/~jt/irmodel.htm

Heterologous expression screens in Nicotiana benthamiana identify a candidate effector of the wheat Yellow Rust Pathogen that associates with processing bodies

Rust fungal pathogens of wheat (Triticum spp.) affect crop yields worldwide. The molecular mechanisms underlying the virulence of these pathogens remain elusive, due to the limited availability of suitable molecular genetic research tools. Notably, the inability to perform high-throughput analyses of candidate virulence proteins (also known as effectors) impairs progress. We previously established a pipeline for the fast-forward screens of rust fungal candidate effectors in the model plant Nicotiana benthamiana. This pipeline involves selecting candidate effectors in silico and performing cell biology and protein-protein interaction assays in planta to gain insight into the putative functions of candidate effectors. In this study, we used this pipeline to identify and characterize sixteen candidate effectors from the wheat yellow rust fungal pathogen Puccinia striiformis f sp tritici. Nine candidate effectors targeted a specific plant subcellular compartment or protein complex, providing valuable information on their putative functions in plant cells. One candidate effector, PST02549, accumulated in processing bodies (P-bodies), protein complexes involved in mRNA decapping, degradation, and storage. PST02549 also associates with the P-body-resident ENHANCER OF mRNA DECAPPING PROTEIN 4 (EDC4) from N. benthamiana and wheat. We propose that P-bodies are a novel plant cell compartment targeted by pathogen effectors

Watson Brake, A Middle Archaic Mound Complex in Northeast Louisiana

Middle Archaic earthen mound complexes in the lower Mississippi valley are remote antecedents of the famous but much younger Poverty Point earthworks. Watson Brake is the largest and most complex of these early mound sites. Wry extensive coring and stratigraphic studies, aided by 25 radiocarbon dates and six huninescence dates, show that minor earthworks were begun here at ca. 3500 B.C. in association with an oval arrangement of burned rock middens at the edge of a stream terrace. The full extent of the first earthworks is not yet known. Substantial moundraising began ca. 3350 B.C. and continued in stages until some time after 3000 B.C. when the site was abandoned. All 11 mounds and their connecting ridges were occupied between building bursts. Soils,formed on some of these temporary surfaces, while lithics. fire-cracked rock. and,fired clay/loam objects became scattered throughout the mound fills. Faunal and floral remains from a basal midden indicate all-season occupation, supported by broad-spectrum foraging centered on nuts, fish, and deer All the overlying fills are so acidic that organics have not survived. The area enclosed by the mounds was kept clean of debris, suggesting its use as ritual space. The reasons why such elaborate activities first occurred here remain elusive. However some building bursts covary with very well-documented increases in El Nino/Southern Oscillation events. During such rapid increases in ENSO frequencies, rainfall becomes extremely erratic and unpredictable. It may be that early moundraising was a communal response to new stresses of droughts and flooding that created a suddenly more unpredictable food base

A systems analysis of the chemosensitivity of breast cancer cells to the polyamine analogue PG-11047

<p>Abstract</p> <p>Background</p> <p>Polyamines regulate important cellular functions and polyamine dysregulation frequently occurs in cancer. The objective of this study was to use a systems approach to study the relative effects of PG-11047, a polyamine analogue, across breast cancer cells derived from different patients and to identify genetic markers associated with differential cytotoxicity.</p> <p>Methods</p> <p>A panel of 48 breast cell lines that mirror many transcriptional and genomic features present in primary human breast tumours were used to study the antiproliferative activity of PG-11047. Sensitive cell lines were further examined for cell cycle distribution and apoptotic response. Cell line responses, quantified by the GI₅₀(dose required for 50% relative growth inhibition) were correlated with the omic profiles of the cell lines to identify markers that predict response and cellular functions associated with drug sensitivity.</p> <p>Results</p> <p>The concentrations of PG-11047 needed to inhibit growth of members of the panel of breast cell lines varied over a wide range, with basal-like cell lines being inhibited at lower concentrations than the luminal cell lines. Sensitive cell lines showed a significant decrease in S phase fraction at doses that produced little apoptosis. Correlation of the GI₅₀values with the omic profiles of the cell lines identified genomic, transcriptional and proteomic variables associated with response.</p> <p>Conclusions</p> <p>A 13-gene transcriptional marker set was developed as a predictor of response to PG-11047 that warrants clinical evaluation. Analyses of the pathways, networks and genes associated with response to PG-11047 suggest that response may be influenced by interferon signalling and differential inhibition of aspects of motility and epithelial to mesenchymal transition.</p> <p>See the related commentary by Benes and Settleman: <url>http://www.biomedcentral.com/1741-7015/7/78</url></p

Single nucleus genome sequencing reveals high similarity among nuclei of an endomycorrhizal fungus

Nuclei of arbuscular endomycorrhizal fungi have been described as highly diverse due to their asexual nature and absence of a single cell stage with only one nucleus. This has raised fundamental questions concerning speciation, selection and transmission of the genetic make-up to next generations. Although this concept has become textbook knowledge, it is only based on studying a few loci, including 45S rDNA. To provide a more comprehensive insight into the genetic makeup of arbuscular endomycorrhizal fungi, we applied de novo genome sequencing of individual nuclei of Rhizophagus irregularis. This revealed a surprisingly low level of polymorphism between nuclei. In contrast, within a nucleus, the 45S rDNA repeat unit turned out to be highly diverged. This finding demystifies a long-lasting hypothesis on the complex genetic makeup of arbuscular endomycorrhizal fungi. Subsequent genome assembly resulted in the first draft reference genome sequence of an arbuscular endomycorrhizal fungus. Its length is 141 Mbps, representing over 27,000 protein-coding gene models. We used the genomic sequence to reinvestigate the phylogenetic relationships of Rhizophagus irregularis with other fungal phyla. This unambiguously demonstrated that Glomeromycota are more closely related to Mucoromycotina than to its postulated sister Dikarya

Combined Associations of a Polygenic Risk Score and Classical Risk Factors With Breast Cancer Risk.

We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio