On 2016 Jan 21, Sebastian Lourido commented:

The conditional dimerizable Cre recombinase (DiCre) has been a powerful technique for conditional genome engineering in Toxoplasma, as first established in this article, and elaborated later (see Pieperhoff, et al. 2015. PLoS One). It has worked well in our hands for a variety of applications. Recently, we discovered that the reporter construct used in this study was cloned down stream and in frame of a Ty-tag (EVHTNQDPLD), such that the KillerRed expressed prior to recombination contains and N-terminal Ty-tag. This observation does not affect any of the experiments presented in the article. However, it might be important to note for future investigators planning further manipulations of the existing DiCre strains or reporter constructs.

On 2015 Sep 24, Bill Cayley commented:

A good example of when "less" is "more" in Obstetric care: https://lessismoreebm.wordpress.com/tag/obstetric-gynegologic/

On 2013 Jul 04, John Overington commented:

A standard for database tag structures would be really useful in general - 1ABC is a PDB code, but it's also many other things, so PDB1ABC would be more general and useful. However, as a database provider this paper highlighted several features that I didn't know and will now explore - e.g. the NLM JATS DTD.

On 2014 Jan 04, Dorothy V M Bishop commented:

I was pleased to see that Professor Farthing took the opportunity to tackle the subject of research misconduct in his lecture. He cogently notes the nature of the problem and makes suggestions to deal with it. I thought his analysis was generally on-target, but I was concerned about his second suggested solution: enhanced monitoring and audit, and his failure to consider an additional approach, which is to change the incentive structure for researchers. The following points are taken from a blogpost I wrote on these topics (http://deevybee.blogspot.co.uk/2013/06/research-fraud-more-scrutiny-by.html).

I agree we need to think about how to fix science, and that many of our current practices lead to non-replicable findings. I just don't think more scrutiny by administrators is the solution.

So what would I do? The answers fall into three main categories: incentives, publication practices, and research methods.

Incentives: Currently, we have a situation where research stardom, assessed by REF criteria, is all-important. Farthing notes that RAE/REF criteria have been devised to stress quality rather than quantity of research, which is a good thing, but it is still the case that too much emphasis goes on the prestige of journals (see http://deevybee.blogspot.co.uk/2013/01/journal-impact-factors-and-ref-2014.html).

Instead of valuing papers in top journals, we should be valuing research replicability. This would entail a massive change in our culture, but a start has already been made in my discipline of psychology :see http://www.nature.com/news/psychologists-strike-a-blow-for-reproducibility-1.14232.

Publication practices: the top journals prioritize exciting results over methodological rigour. There is therefore a strong temptation to do post hoc analyses of data until an exciting result emerges. I agree with Farthing that pre-registration of research projects is a good way of dealing with this. I'm pleased to say that here too, psychology is leading the way in extending research registration beyond the domain of clinical trials: http://blogs.lse.ac.uk/impactofsocialsciences/tag/registered-reports/

Research methods: we need better training of scientists to become more aware of the limitations of the methods that they use. Too often statistical training is a dry and inaccessible discipline. All scientists should be taught how to generate random datasets: nothing is quite as good at instilling a proper understanding of p-values as seeing the apparent patterns in data that will inevitably arise if you look hard enough at some random numbers. In addition, not enough researchers receive training in best practices for ensuring quality of data entry, or in exploratory data analysis to check the numbers are coherent and meet assumptions of the analytic approach.

Finally, before any new regulation is introduced, there should be a cold-blooded cost-benefit analysis that considers, among other things, the cost of the regulation both in terms of the salaries of people who implement it, and the time and other costs to those affected by it. My concern is that among the 'other costs' is something rather nebulous that could easily get missed. Quite simply, doing good research takes time and mental space of the researchers. Most researchers are geeks who like nothing better than staring at data and thinking about complicated problems. If you require them to spend time satisfying bureaucratic requirements, this saps the spirit and reduces creativity.

I think we can learn much from the way ethics regulations have panned out. When a new system was first introduced in response to the Alder Hey scandal, I'm sure many thought it was a good idea. It has taken several years for the full impact to be appreciated. The problems are documented in a report by the Academy of Medical Sciences, which noted "Urgent changes are required to the regulation and governance of health research in the UK because unnecessary delays, bureaucracy and complexity are stifling medical advances, without additional benefits to patient safety"

On 2014 May 03, Stefanie Butland commented:

All interaction data from this paper are freely available at IntAct http://www.ebi.ac.uk/intact/query/24705354 and are featured as Dataset of the Month for May 2014. These include 312 binary interactions from yeast two-hybrid, anti tag coimmunoprecipitation, fluorescence microscopy and luminescence based mammalian interactome mapping (LUMIER) experiments.

We submitted our data directly to IntAct through the IMEx Consortium as part of the publication process. I encourage others to consider this route to making your data available for re-use and re-mixing as the expert biocuration service provided by IntAct was smooth, accurate, and required very little of our time. A very positive experience.

On 2014 Oct 06, Leonid Teytelman commented:

Dear Authors,

We have published an analysis in S. cerevisiae, showing expression-dependent artifactual ChIP enrichment at highly expressed loci (Teytelman L, 2013 "Highly expressed loci are vulnerable to misleading ChIP localization of multiple unrelated proteins"). As you know, our finding raises the question of whether HOT regions may also be influenced by the same artifact.

It is great that you have considered our work and have thoughtfully responded to our analysis. Below, I would like to continue this discussion in an effort to better understand the artifact, its causes, and whether it may be contributing to the enrichment at the HOT loci.

1. “we have demonstrated that there is no correlation between our non-specific binding controls (IgG) and our measured transcription factor occupancy;”

Considering our results with no-tag control experiments, an IgG may fail to control for the artifact. It would be great if you could instead perform a GFP ChIP-Seq, similarly to what we have done in yeast.

2. The regions determined in ref. 41 have very low enrichment (twofold or less) of non-specific immunoprecipation in anti-GFP antibody controls over input DNA evaluated using a non-standard sliding-window approach. Importantly, immunoprecipitation/input ratios at this level are typically not considered enriched for binding in modern peak-calling procedures. For example, the median immunoprecipitation/input ratio for our human RNA Pol II experiments is 20-fold, and only 0.033% of human RNA Pol II peaks contain an immunoprecipitation/input ratio ≤ twofold.

The mean is low, but in both anti-GFP experiments, there are loci with 3-5x enrichment (figure 4D). Most importantly, while the anti-GFP enrichment at the hyper-ChIPable loci is low, please note that the level of enrichment is variable from protein to protein (2-5X for Sir proteins, but often >10X for Cse4).

3. Thus, it is essential to note that the term ‘hyper-ChIPable’, coined by ref. 41, is quite misleading, as a correctly performed ChIP experiment will evaluate statistically enriched regions, with higher immunoprecipitation/input ratios. The so-called hyper-ChIPable regions in ref. 41 are not binding regions as determined under ChIP-seq best practices. Hence, when statistical peak-calling was performed in ref. 41 (using the established MACS peak-caller) to evaluate signals only at significantly enriched regions (Supplementary Table 1) only 17 (<7.5%) of the 238 claimed ‘hyper-ChIPable’ regions were called significant by all three Sir proteins. In fact, 68% of their 238 regions do not contain a binding site for any Sir protein as determined by MACS, despite even very liberal settings used (P < 10−5, no fold enrichment cut-off). Thus, the data of ref. 41 contradict its own major claim that all three Sir proteins showed enrichment at the 238 sites.

By reporting the 238 sites with >2fold enrichment of Sir2, Sir3, and Sir4, we are in fact being extra-demanding in terms of the threshold. We are stringently requiring all three proteins to be enriched above a threshold at the locus. So a target with 5x enrichment of Sir2 and 1.8X enrichment of Sir3 would not pass this cutoff. A typical ChIP study will focus on a single factor at a time. Had we done that, we would have many more artifactual targets for each silencing protein, with many at 5x or higher enrichment. Furthermore, the level of the artifactual signal varies from protein to protein or experiment to experiment. For example, the Cse4 signal at highly-expressed loci can give 10x or higher enrichment.

4. Furthermore, as indicated in Supplementary Table 3 of ref. 41, the Sir2, Sir3 and Sir4 ChIP-seq experiments were performed only once each, which raises the question as to whether enrichment of Sir proteins at the 238 sites is reproducible. More rigorously, even for the remaining 17 genomic loci, their status as hyper-ChIPable is questionable as each region would first have to be established as a reproducible binding site in replicate experiments for each individual Sir protein. If you consider that Sir2, Sir3 and Sir4 ChIP-seq constitutes three replicates of Sir proteins, their data show that most of their claimed sites were not reproducibly enriched.

Most of our artifact-cause analysis focuses on genome-wide data, not on the 238 sites. The 238 Sir-enriched euchromatic loci were a launching point for the analysis, but most of the paper looks comprehensively at the link between expression and ChIP levels. Figures 3, 4, and 5 are all on genome-wide correlations between Pol II/III and ChIP.

As for reproducibility, we see the same peaks, with often 10x enrichment, in Ste12, Cse4, two distinct GFP experiments, and each of the three Sir ChIP-Seq datasets. The same exact loci come up in the Sir3 paper from Oliver Rando’s group (Radman-Livaja M, 2011).

5. In addition to the analytical differences outlined above, other potential sources for the marked differences between our data and the Sir-enriched regions of ref. 41 are deviations from a typical ChIP protocol. In particular, ref. 41 employed a significantly longer cross-link time (1 h as opposed to the typical 10–20 min). This might contribute to formation of large non-specific protein–DNA complexes, which can in turn increase non-specific immunoprecipitation.

Though not discussed in the manuscript, we have in fact performed experiments to investigate if the crosslinking concentration contributed to the misleading signal. We performed ChIP with the 1 hour crosslinking at room temperature at the following formaldehyde concentrations: 0.0625%, .125%, .25%, .5% and 1%, but did not find a proportionate decrease in the hyper ChIPpable signal with the decreasing formaldehyde concentrations. Moreover, the presence of hyper-ChIPability in the Snyder datasets (Cse4, Ste12), ours (Sir2, 3, 4, GFP), and Rando (Sir3) make it clear that the problem is not in some unusual protocol steps in our hands.

We also note that we initially performed the Sir ChIP-Seq experiments because of our interest in the Sir protein biology. Because the Sir proteins do not directly interact with the DNA, we used longer crosslinking times. This is not unique to our work.

In summary, much more work is needed to pinpoint the cause of the artifact and to evaluate whether some or all of the signal at highly expressed genes in many other reported ChIP studies could be artifactual. Much more work is necessary to develop the best controls and corrections for the artifact. However, the artifact we report is not minor and is not a consequence of the methodological details of our manuscript.

Also, please note the following papers, published almost in parallel with ours, on this topic:

Park D, 2013 "Widespread Misinterpretable ChIP-seq Bias in Yeast" (Different analysis methods but the same conclusions in S. cerevisiae, analyzing an entirely different set of factors with ChIP-Seq experiments.)

Kasinathan S, 2014 "High-resolution mapping of transcription factor binding sites on native chromatin" (Questions specificity of standard ChIP in S. cerevisiae and at HOT regions of Drosophila. This work possibly provides a solution to the artifact with a modification of the ChIP technique.)

Also, the following discussion of our work on PubPeer may be useful.

On 2014 Oct 21, George McNamara commented:

This is a nice paper. The abstract refers to using 24 epitope tags (24mer), much of the paper uses a 10mer. Just doing GFP is boring. When I came up with the "Tattletales" (TALE-FPn ... I came up with the idea before sgRNA:Cas9 became popular), I immediately realized that multimerizing FP biosensors. The current paper is the same as my what I refer to as "Binary Tattletales", as in: 1. TALE-(linker-epitope tag)n 2. "binder"-(linker-FP)m with Tattletales being T-cells -- TALE FPs/Biosensors. Since I moved to MD Anderson Cancer Center, the first T now refers to "T-cells and Tumor cells". Likewise T-bow refers to rainbow T-cells and Tumor cells for promoter bashing and otherwise multicolor dots labeling cells (rainbow in homage of course to Brainbow mice etc, and especially to real rainbows). For more on Tattletales, Binary Tattletales, and T-Bow, see http://works.bepress.com/gmcnamara/63 http://works.bepress.com/gmcnamara/42

Giving credit where credit is due: The authors really should have cited the first mammalian cell paper localizing a lot of FPs in one spot (they came 'close' with a Gordon 1997 Cell paper on GFP:LacO in E.coli, but the Tanenbaum paper is all mammalian cells): Robinett et al 1996 JCB http://www.ncbi.nlm.nih.gov/pubmed/8991083 http://jcb.rupress.org/content/135/6/1685.long See their figure 4A. Straight, Robinett et al also published a yeast paper in 1996, http://www.ncbi.nlm.nih.gov/pubmed/8994824 and it would have been useful to cite that.

The PDF download at http://works.bepress.com/gmcnamara/63 has a table of 130 FP biosensors (if you are Laconic about ATeam and Fire, too bad) and an extensive reference list with ZF-FP, TALE-FP, Cas9-FP (the latter from the Weissman group), and more (PUF's and PPR's are RNA binding protein families with structural similarities to TALEs). My favorite name -- besides Tattletales and T-Bow, of course -- is "TALE-Lights" from Yuan, Shermoen, O'Farrell 2014, http://www.ncbi.nlm.nih.gov/pubmed/24556431

On 2014 Oct 27, David Colquhoun commented:

For all the reasons given by Hilda Bastian (and a few more, like P = 0.04 provides lousy evidence) it astonishes me that this study should have been trumpeted as though it represented a great advance. That's the responsibility of Nature Neuroscience (and, ultimately, of the authors).

I wonder whether what happens is as follows. Authors do big fMRI study. Glamour journal refuses to publish without functional information. Authors tag on a small human study. Paper gets published. Hyped up press releases issued that refer mostly to the add on. Journal and authors are happy. But science is not advanced.

I certainly got this impression in another recent fMRI paper in Science. Brain stimulation was claimed to improve memory (P = 0.043)

I guess these examples are quite encouraging for those who think that expensive glamour journals have had their day. Open access and open comments are the way forward.

On 2017 Jul 09, Jeffrey Ross-Ibarra commented:

In our manuscript exploring the population genetics of local adaptation (Tiffin and Ross-Ibarra 2014) we included a discussion about the potential uses of reduced representation data (e.g. RAD-seq, GBS). To provide a sense of the probability of using reduced representation data to identify targets of selection, we included a figure showing the probability of having a SNP included in a region of the genome in which diversity had been severely reduced due to a recent selective sweep. Unfortunately this figure is not correct; an error in the code inadvertently used centimorgans as morgans, causing the recombination rate to be off by a factor of 100.

To correct this we have generated a new figure (see http://rpubs.com/rossibarra/257207; raw code is available at https://gist.github.com/rossibarra/be44cc3b3796f45840d942ad11c01ba1) that corrects this error and presents a more realistic model. Our previous model assumed SNPs were distributed evenly across the genome and the presence of a single SNP near a sweep was sufficient for detection. Instead, here we explicitly model sequence “tags” coming from RAD-seq or GBS, and incorporate information about the variation in diversity expected among tags in neutral regions of the genome. The figure clearly shows that with dense marker coverage and strong selection, the probability of detecting reductions in diversity due to recent selective sweeps from new beneficial mutations can be relatively high. We emphasize, however, that the purpose of the figure is solely to develop an intuition of the likelihood of detecting a recent selective sweep. The many simplifying assumptions made in generating the figure (no recent demographic change, both sequence tags and recombination occur uniformly along the genome, selection is on a novel beneficial mutation with additive effect that has recently swept to fixation), as well as the specific mutation rates, sample size, sequence length, and recombination rates assumed will all affect the actual probability of a tag being included in a selective sweep. Moreover, this figure does not touch on many other relevant issue such as multiple testing, complex demography, background selection, or other modes of positive selection (e.g. from standing variation, balancing selection, or selection on polygenic traits).

We have submitted a correction to the journal.

We thank Eric Johnson for drawing our attention to the error, and Eric Johnson, Kathleen Lotterhos, and Graham Coop for kindly reviewing previous versions of the code and assumptions we have used in generating this new figure.

On 2015 Sep 09, Bill Cayley commented:

A good example of when less is more in cardiac care - a collection of related examples is at: https://lessismoreebm.wordpress.com/tag/cardiovascular/

On 2017 Jul 09, Sunil Verma commented:

Comment on - Evaluation of Bar, Barnase, and Barstar recombinant proteins expressed in genetically engineered Brassica juncea (Indian mustard) for potential risks of food allergy using bioinformatics and literature searches

Sunil Kumar Verma, Principal Scientist CSIR-Centre for Cellular and Molecular Biology, Hyderabad 500 007, India.

In this study, the authors have tested the allergenic potential of the transgene Bar, Barnase, and Barstar expressed in Genetically Modified Indian Mustard for heterosis breeding. To this end, the authors have done the primary amino acid sequence comparisons of these proteins with the primary amino acid sequences of the known allergens listed in Allergenonline.org and NCBI Entrez protein database until January 2015 and 9 March 2015, respectively. Based on these bioinformatics comparisons authors concluded that the Bar, Barnase and Barstar proteins are unlikely to present any significant risk of food allergy to consumers. The authors also recommended not to perform any human serum IgE testing to further evaluate possible binding to the Bar, Barnase or Barstar proteins.

I hereby propose that the above conclusions drawn by the authors in this study are incorrect and require a major revision.

The main criteria used by the authors in these bioinformatics comparisons was the primary amino acid sequence homology searches of the proteins in question with that of the primary amino acid sequences of the potential allergen listed in above databases. All the hits with less than 50% primary amino acid sequence identities for full length proteins and less than 35% identity in the sliding window 80 amino acid segments of each proteins were ignored; the argument was that these matches could not have led to significant structural similarities among the proteins in question, therefore can be ignored.

Several independent studies have shown that in many cases, even though the primary amino acid sequence similarity between two proteins / domains are very less (<20%), but the tertiary structures of the proteins may be highly similar. One classical example of this is high structural similarity between N terminal half of the Krit-B41 domain with that of the RA domain of RalGDS (1RAX:A) with an r.m.s. deviation of 2.9A for 80 aligned positions; despite a very low homology in their primary amino acid sequences (sequence identity =8.7%). [1, S1] It is notable that both RalGDS and Krit-1 interact with Rap1A through the RA and B41 domains, respectively [2, 3], and so the talin [4]. Thus, the high primary amino acid sequence similarity between two proteins may though infer greater chances of structural homology between these proteins; however, low primary amino acid sequence similarity does not necessarily infer that proteins in question will necessarily have higher structural dissimilarities.

Since it is the conformationally determined structure of the proteins/epitopes which finally decide immunogenicity and allergenicity - and not just the primary amino acid sequences; the conclusion drawn in this study based on merely the primary amino acid sequence comparisons are scientifically inappropriate.

Secondly, in real scenario, both the Barnase and Barstar proteins are expressed simultaneously and these two proteins remain in a complex and not as individual proteins in plant [5, 6]. It is not unlikely that structure of a specific protein in complex may be different than that of the structure of the same individual protein in free form. Also, there may be the possibilities of formation/exposure of new epitope(s) surfaces, particularly as we know now that there are several antibodies known that recognize just the native proteins and some may indeed require complex assembly.

Thus, these conformationally determined epitopes that are recognized in the complex but not the free protein of interest may be reveled in differential screening between a protein and a complex form of the same protein. The conformationally determined epitopes could then be compared for structural homology with the epitopes in known allergens to determine the allergenic potential of two proteins in complex; such studies however, were not conducted in this paper; and the fact that Barnase and Barstar remain in complex and not in free form, was completely ignored throughout the study.

Finally, I found that the overall implication of the Allergenonline.org database itself on correctly predicting the allergenic potential of a new antigen was also questionable.<br> To test this, I assumed that 'Ani s 9' (which is a very well known allergen from SXP/RAL-2 protein family) [7] is a new putative allergen and that this group of proteins are not yet listed in the database; and asked whether or not one can predict if 'Ani s 9' is a potential food allergen using the strategy as was used in this study for Barnase, Barstar and Bar transgenic proteins. The full length primary amino acid sequence comparison of 'Ani s 9' (GenBank: ABV55106.1) using default parameter i.e 'E' value cut off = 1 identified 7 hits (excluding the hits with its own sequences) with 'tropomyosin' allergen from various organisms and 'AAEL002761-PC ' allergen from Aedes aegypti, respectively; however, none of the hits was with significant similarity cut off (>50%). Thus, this bioinformatics search criteria wrongly predicted that the 'Ani s 9' is not a potential food allergen. [S2]

The another criteria i.e. greater than 35% identity in the sliding window of 80 amino acid segment also did not produce any hit at all (other than self hits, which were excluded as explained above), indicating that this criteria also failed to identify 'Ani s 9' as potential food allergen. [S3] The third criteria i.e. 8 continuous amino acid segment search also did not identify any hit with any of the allergen in the database.[S4]

Thus, the bioinformatics search as used in this study following any of the criteria defined could not identify 'Ani s 9' as a potential food allergen. This confirms that the criteria used in this study by authors could easily give false negative results.

The only strategy that could have identified 'Ani s 9' as possible food allergen was a '6 continuous amino acid segment search, which could have identified its match with Allergen 'Lol p 5' for the 6-aa segment 'ANAPPA'. [S5]

This criteria however, was not used in current study to predict the allergenic potential of Bar, Barnase and Barstar. If this specific criteria was used, Barnase transgenic protein also could have given a potential hit with Allergen Ber e 2 and Ani s 9 for the 6 continuous amino acid patch LFSTAA, and WVASKG, respectively [S6]; hence, the conclusion of this paper could have been different.

In view of the above, I conclude that the criteria implemented in this study were not sufficient to exclude the possibility of the transgenic protein Bar, Barnase and Barstar being a possible allergen; therefore the conclusion drawn by authors that "the above transgenic proteins are unlikely to present any significant risk of food allergy to consumers" is not beyond a reasonable doubt, and hence need an appropriate correction by the way of erratum.

Further, as discussed above, the Barnase and Barstar proteins are expressed simultaneously in final plant and they remain in a tight complex (i.e. barnase-barstar complex) and not as free form. The current study has not even touched upon the barnase-barstar complex; therefore, until the systematic studies on this complex is conducted and concluded, it is not appropriate to give a 'safe' tag to these transgenic proteins. This is particularly important since the conclusion drawn from this study was one of the major evidence which was used by the Indian regulatory authorities to recently give a safety clearance to the genetically engineered Brassica juncea (Indian Mustard) for commercial cultivation in India. [8, 9]

Ref & Suppl Information

On 2015 Sep 26, Eric Fauman commented:

I applaud the authors for identifying novel genetic associations with metabolites but I disagree with their interpretations and conclusions in several regards.

As tempting as it is to use eQTL data to assign causal genes to SNPs it is frequently seen that SNPs tag expression of unrelated genes as often as they tag the true causal gene for the given trait.

In this study the most obvious example is at rs2066938 where the authors report eQTL associations with 5 egenes (RNF10, MLEC, UNC1198B, CAMKK and COQ5), but not ACADS which is almost certainly the true causal gene, as the authors acknowledge in the text.

At the ARG1 and CRAT loci, other genes have stronger eQTL signals so here too the eQTL data is incomplete.

The ALMS1/NAT8 locus is less clear, but previous authors have assigned this locus to NAT8 given the association with N-acetylornithine and NAT8's presumed acetylation function. The biochemical linkage of N-acetylornithine and arginine in the urea cycle suggests that NAT8 is also the causal gene for this paper. If NAT8 is truly the causal gene, the eQTL data missed it at this locus.

A striking example of the over-reliance on eQTL data in this paper is at the "PPP1R16A" locus which associates with the ratio of aspartic acid to alanine. This SNP is in fact just upstream of GPT which encodes glutamic-pyruvic transaminase, also known as alanine transaminase. GPT is a far more plausible causal gene even though it is not one of the 10 egenes listed for this SNP. Interestingly, there is a coding variant in GPT in reasonable LD with the lead SNP (rs1063739, r2=0.77).

In fact 6 of the loci are linked to coding variants in the most probable causal gene (NAT8, GPT, ACADS, SLC22A16, MCCC1 and CPS1).

Again, it's great to see new SNP-metabolite associations still emerging. However any GWAS interpretation must make use of all biological lines of evidence and not rely only on one or two types of data or analysis.

On 2016 Nov 29, James C Coyne commented:

This study makes some dubious claims that should be subject to independent scrutiny and re- evaluation. It was published in APA journal, which requires sharing of data upon request. However, as I detail and document below, the author responded to a request for just a few variables with an invoice for $450 and a demand that an independent researcher sign a contract not to depart from some arbitrary limits on reanalysis. This sort of behavior threatens routine data sharing. It is deplorable that the American Psychological Association does not support their members to exercise their right to data. See the blog post below for documentation.

https://jcoynester.wordpress.com/2016/11/29/a-quixotic-quest-to-obtain-a-dataset-on-media-violence-with-an-unexpected-price-tag/

On 2016 Apr 18, Gwangseong Kim commented:

In two recent articles [1, 2] two techniques for removing or inactivating blood borne pathogens were introduced. The initial experiments were performed in vitro under simplified conditions. First, the primary achievement of the PDT work deserves clarification [1]. PDT is a powerful therapeutic modality, but its clinical application has been hampered by the inability of light to penetrate deep layers of the tissue, which is mainly due to hemoglobins in the blood readily absorbing photons. Utilizing a millimeter- diameter transparent tube for extracorporeal blood circulation allows PDT to function well despite the presence of hemoglobins in blood. Another point that deserves clarification is that the tube capturing device is not a microfluidic device [2]. This technique can be adapted using existing medical tubing without the need for complicated microfluidics and micro-fabrication. The device is a medical tube that has been chemically modified using simple steps to adapt the internal surface for cell capturing. We would like to take this opportunity to respond to concerns brought up in [3]. We start off by addressing concern (1), which speculates about the possibility of overheating during the use of near IR light. Our control data (Fig.3 and Fig.4 of [1]), confirmed that controls illuminated without photosensitizer-antibody conjugates did not undergo cell death, whereas those with photosensitizer-antibody conjugates underwent significant cell death under identical conditions. Thus it is clear from our data that temperature did not affect the outcome. It has been shown that 660 nm irradiation is safe and effective [4-6]. Moving on to concern (2) part (a) that brings up the problem of using the CD-44 antigen as a target. Limitations of antibody specificity are common knowledge and not unique to CD-44, but to all antibodies. To our knowledge, a targeting method that exclusively binds only to cancer cells does not yet exist, making the use of such a compound an unreasonable standard for publication. We used CD-44 antibody to demonstrate feasibility. As targeting methodologies advance and better selectivity to target cells becomes available, this technique will have improved selectivity. Our experiments were designed to avoid non-specific damage to other cells by pre-staining pure cancer cells with the photosensitizer-antibody conjugates and subsequently removing extra free conjugates before spiking into blood (described in detail in [1]). This elimination of the possibility of side effects due to undesired binding to other blood cells and excess free photosensitizer-antibody conjugates precluded the need for a toxicity study, particularly because we were at the proof-of-principle stage. Part (b) of concern (2) suggests that we may have caused non-specific damage to non-cancerous cells by ROS' convection in the blood stream. We believe that this is highly unlikely. One of the authors has been conducting research focusing on ROS and PDT for years, in collaboration with other researchers [7-15]. This research demonstrated that PDT is extremely selective to targeted cells [13]. Part (c) of concern (2) states that we should have used additional cytotoxicity assays, such as Annexin V, TUNEL, and MTT. However, because none of these techniques are cell-type specific, they would be useless for the particular objective they were suggested. Once our line of investigation reaches a more mature stage, we plan to undertake more useful studies, such as applying separate fluorescent tags, or radio labels, in addition to a cell viability assay and analyzing cell death with a cell sorting technology, such as FACS, MACS, density gradient centrifugation, etc. Concern (3) is that the capturing work [2] lacked purity confirmation concerning non-specific capturing of blood cells. Though purity confirmation is critical in diagnostic testing, our work was strictly limited to in vitro conditions, using spiked pure PC-3 cells as a model. To visualize and quantify PC-3 cells in the presence of whole blood, PC-3 cells were pre-labeled using a fluorescence tag (Calcein AM) and the extra free dye was subsequently removed before spiking PC-3 cells into blood. Because only PC-3 cells can have fluorescence in the blood mixture, and because quantification was based on fluorescing cells, false-positive results from other blood cells can be reasonably excluded. Furthermore, if other blood cells were captured but not identified by our detection method our data would then indicate that the simple tube captured cancer cells despite being blocked by other blood cells. If our technique were applied to CTC diagnosis, independent isolation procedures could be used to ensure the purity of captured cells. In contrast, if used for removal or killing, the purity of captured cells would not be as critical, provided that CTCs are effectively removed. If, by chance, capturing is hampered by accumulation of non-specific binding in filtering the entire blood volume, this issue can be addressed with strategies such as scaling up the tube and carefully determining the tube dimensions, flow rate, frequency of tube replacements, etc. Finally, concern (4), points out that the experimental conditions were not translatable to clinical applications. Part (a) regards scaling up the system to show high throughput. The concept of extracorporeal blood processing of the entire blood volume has been used for years in cases such as hemodialysis. We already are working on optimizing the technique for larger blood volume processing. Part (b) of concern (4) discusses the static no-flow condition as being unrealistic. This issue was brought up during the review process, and we provided with our results showing data under constant flow conditions by peristaltic pump (to be published in future publication). The reviewers agreed that the use of a no-flow condition as a conservative approach during a proof-of-concept stage was appropriate. Despite its preliminary nature, we believe that our work communicates novel ideas, an important objective of research and publication. Given the number of research articles dealing with diagnostics and microfluidics, perhaps a further point of confusion came about by thinking of our work in those terms. We want to clarify that diagnostics were not the primary objective in our work. Furthermore, as it becomes evident by this response our experimental design was carefully devised to minimized unnecessary interferences. We hope that this response mitigates any confusion and addresses the concerns raised. The entire response appears in the PLOS1 comment section under response: http://www.plosone.org/article/comments/info:doi/10.1371/journal.pone.0127219. Feel free to contact us for further clarifications.

1. Kim G, Gaitas A. PloS One. 2014;10(5):e0127219-e.
2. Gaitas A, Kim G. PLoS One. 2015;10(7):e0133194. doi: 0.1371/journal.pone.0133194.
3. Marshall JR, King MR. DOI: 101007/s12195-015-0418-3. 2015;First online.
4. Ferraresi C, et al. Photonics and Lasers in Medicine. 2012;1(4):267-86.
5. Avci P, et al. Seminars in cutaneous medicine and surgery; 2013.
6. Jalian HR, Sakamoto FH. Lasers and Light Source Treatment for the Skin. 2014:43.
7. Ross B, et al. Biomedical Optics, 2004
8. Kim G, et al. Journal of biomedical optics. 2007;12(4):044020--8.
9. Kim G, et al Analytical chemistry. 2010;82(6):2165-9.
10. Hah HJ, et al. Macromolecular bioscience. 2011;11(1):90-9.
11. Qin M, et al. Photochemical & Photobiological Sciences. 2011;10(5):832-41.
12. Wang S, et al. et al. Lasers in surgery and medicine. 2011;43(7):686-95.
13. Avula UMR, et al.Heart Rhythm. 2012;9(9):1504-9.
14. Kim G, et al. R. Oxidative Stress and Nanotechnology, 2013. p. 101-14.
15. Lou X, et al. E. Lab on a Chip. 2014;14(5):892-901.

On 2016 Jun 21, Evelina Tutucci commented:

We have also recently discussed Nelles et al. Nelles DA, 2016. Since we are interested in developing new techniques for studying gene expression and mRNA localization at the single molecule level, a potential tag-less system to detect mRNAs in fixed and live cells would be a further advance. As pointed out by the Duke RNA Biology journal club we think that Nelles et al. represents an attempt to apply the Cas9 System to detect endogenous mRNA molecules. Unfortunately, no evidence is presented to demonstrate that this system is ready to be used to study gene expression at the single molecule level, as the MS2-MCP system allows. The RNA letter by Garcia and Parker Garcia JF, 2015 showed that in S. cerevisiae the binding of the MS2 coat protein to the MS2-loops diminished tagged mRNA degradation by the cytoplasmic exonuclease Xrn1. However, these observations were not extended to higher eukaryotes. Previous work from our lab described the generation of the beta-actin-MS2 mouse, whereby all the endogenous beta-actin mRNAs were tagged with 24 MS2 loops in the 3’UTR (Lionnet T, 2011, Park HY, 2014). This mouse is viable and no phenotypic defects are observed. In addition, control experiments were performed to show that the co-expression of the MS2 coat protein in the beta-actin-MS2 mouse allowed correct mRNA degradation and expression (Supplementary figure 1b, Lionnet T. et al 2011). Furthermore, multi-color FISH (Supplementary figure 6, Lionnet T. et al 2011) showed substantial co-localization between the ORF FISH probes and MS2 FISH probes, demonstrating the validity of this model. We think that the observations by Garcia and Parker are restricted to yeast because of the short half-life of their mRNAs, wherein the degradation of the MS2 becomes rate-limiting. Based on our extensive use of the MS2-MCP system, we think that higher eukaryotes may have more time to degrade the high affinity complexes formed between MS2-MCP, providing validation for this system to study multiple aspects of gene expression. In conclusion, we think that the MS2-MCP system remains to date the best method to follow mRNAs at the single molecule level in living cells. For the use of the MS2-MCP system in S. cerevisiae we have taken the necessary steps to improve it for the study of rapidly degrading mRNAs and are preparing this work for publication.<br> Evelina Tutucci and Maria Vera, Singerlab

On 2016 Jul 27, Duke RNA Biology Journal Club commented:

This is a summary of a journal club discussion:

This is one of four articles using similar imaging techniques to study translation in living cells published at the same time. These publications add to the growing number of techniques used to image translation such as mature fluorescent proteins Yu J, 2006, TRICK Halstead JM, 2015, and RNA-binding protein/mRNA co-fluorescence Wu B, 2015. The technique presented in this article is similar to the last except that it uses Suntag to image the nascent chain and PP7 aptamers on the mRNA. The colocalization of the two represents active translation in polysomes.

The technique is novel because co-localization is detected as the protein is translated. This brings fluorescent V4-peptide antibodies into concentrated foci at a single point, and can thus be used to follow multiple rounds of translation. Because of this, only detection of the translated protein is needed and indeed, past the first figure, the mRNA fluorescence is not shown. Fast changes in translation can be detected as shown using the ATF4 ORF construct translational response to stress shown in Figure 4 with the possibility of extending the time of tracking to hours by anchoring the mRNA Yan X, 2016 or using fast 3D imaging techniques. One unusual observation the authors made was the vast heterogeneity of transcript translation within a single cell; at any given time only a subset of the transcripts undergo translation and translation rates may vary depending on as yet unknown factors. A related observation is the diffusion of polysomes within the cell: polysomes translating cytosolic transcripts have slower diffusion rates in the perinuclear region of the cell compared to the cytoplasm. This could be due to the restrictive architecture of a membranous area but the exact mechanism remains unknown. A second surprising observation indicates mRNAs that have begun translation and are associated with polysomes can be transported in dendrites, contrary to earlier reports Besse F, 2008. However, the authors cannot detect if translation is temporarily stalled during transport.

While this technique makes substantial findings in the area of single transcript translation behavior, there are limitations. All in all, these images are dots that respond to translation inhibitors, meaning the resolution is not good enough to detect codon resolution and should be coupled with other techniques to verify observations and determine their mechanism. Additionally, since detection of the nascent chain wouldn’t be detected until the majority of the V4 peptides were translated, initiation would be overlooked; however, TRICK is an existing technique for studying the first round of translation.Our main criticism with this technique is the extensive construct engineering that must be performed which raises concerns over disturbing the mRNA and protein functions from both the PP7 aptamers, the Suntag peptides and an ornithine decarboxylase tag to facilitate rapid degradation of the protein. These engineering steps add over 2 kb to the original gene. Additionally, an antibody against the Suntag and a fluorescent PP7 coat protein must be expressed in the cytosol. While the constructs studied did not cause harm to the cell, each construct of interest must be tested individually. Along this line, while there is the possibility to multiplex by changing the aptamer loop or peptide-antibody combination, it would be difficult to multiplex above two individual transcripts. Thus large-scale studies involving individual translation dynamics of mRNA subsets would remain time consuming and technically challenging.

A quick comparison with the three other papers show agreements among all of them Iwasaki S, 2016 however, there is a great opportunity to learn by reading the papers to compare experimental approaches of three groups. We look forward to see what novel findings this technique uncovers as it becomes adopted in different laboratories.

On 2016 Jun 02, Michael Tatham commented:

Is SUMO5 a pseudogene?

There are known to be many SUMO pseudogenes in humans (http://www.ncbi.nlm.nih.gov/pubmed/12383504). A fair position when confronted with a claim that a new SUMO paralog has been discovered is to assume it is a non-expressed pseudogene until otherwise convincing evidence is provided. This paper lacks one piece of critical evidence supporting the idea that SUMO5 really exists as a protein, and that is the presence of endogenous protein.

When BLAST searched, the nucleotide sequence of SUMO5 (originally termed SUMO13 according to the authors’ GenBank entry: FJ042790.1), returns a top hit of “Homo sapiens SUMO1 pseudogene 1 (SUMO1P1), non-coding RNA Sequence ID: ref|NR_002189.3|”. The only difference is a single nucleotide T23 (in SUMO13/SUMO5), which is C in SUMO1P1. This may be a primer synthesis error or a DNA sequencing error.

To put beyond reasonable doubt that SUMO5 is not a pseudogene at least two pieces of new experimental evidence showing SUMO5 is expressed in cells is required. I can think of three good ways to do this:

(1) Mass-spectrometric evidence of a peptide unique to SUMO5.

(2) Cross-reaction of a SUMO5-specific antibody with an endogenous protein.

(3) Editing of the genome to insert an epitope tag into the endogenous SUMO5 gene, with the intention of detecting the protein using an antibody specific to the tag.

All three of these pieces of evidence will be strengthened by parallel studies comparing cells with and without SUMO5-specific knock-down.

RTPCR experiments intending to detect mRNA are particularly uninformative given that DNA contamination often leads to false-positives. This is especially true for SUMO5 given the fact the gene is intronless, a notable characteristic of pseudogenes.

On 2016 Sep 16, Hilda Bastian commented:

There are many important issues raised in this paper on which I strongly agree with John Ioannidis. There is a lot of research waste in meta-analyses and systematic reviews, and a flood of very low quality, and he points out the contributing factors clearly. However, there are some issues to be aware of in considering the analyses in this paper on the growth of these papers, and their growth in comparison with randomized and other clinical trials.

Although the author refers to PubMed's "tag" for systematic reviews, there is no tagging process for systematic reviews, as there is for meta-analyses and trials. Although "systematic review" is available as a choice under "article types", that option is a filtered search using Clinical Queries (PubMed Help), not a tagging of publication type. Comparing filtered results to tagged results is not comparing like with like in 2 critical ways.

Firstly, the proportion of non-systematic reviews in the filter is far higher than the proportion of non-meta-analyses and non-trials in the tagged results. And secondly, full tagging of publication types for MEDLINE/PubMed takes considerable time. When considering a recent year, the gulf between filtered and tagged results widens. For example, as of December 2015 when Ioannidis' searches were done, the tag identified 9,135 meta-analyses. Today (15 September 2016), the same search identifies 11,263. For the type randomized controlled trial, the number tagged increased from 23,133 in December to 29,118 today.

In the absence of tagging for systematic reviews, the more appropriate comparisons are using filters for both systematic reviews and trials as the base for trends, especially for a year as recent as 2014. Using the Clinical Queries filter for both systematic reviews and therapy trials (broad), for example, shows 34,126 for systematic reviews and 250,195 trials. Page and colleagues estimate there were perhaps 8,000 actual systematic reviews according to a fairly stringent definition (Page MJ, 2016) and the Centre for Reviews and Dissemination added just short of 9,000 systematic reviews to its database in 2014 (PubMed Health). So far, the Cochrane Collaboration has around 38,000 trials in its trials register for 2014 (searching on the word trial in CENTRAL externally).

The number of systematic reviews/meta-analyses has increased greatly, but not as dramatically as this paper's comparisons suggest, and the data do not tend to support the conclusion in the abstract here that "Currently, probably more systematic reviews of trials than new randomized trials are published annually".

Ioannidis suggests some bases for some reasonable duplication of systematic reviews - these are descriptive studies, with many subjective choices along the way. However, there is another critical reason that is not raised: the need for updates. This can be by the same group publishing a new version of a systematic review or by others. In areas with substantial questions and considerable ongoing research, multiple reviews are needed.

I strongly agree with the concerns raised about conflicted systematic reviews. In addition to the issues of manufacturer conflicts, it is important not to underestimate the extent of other kinds of bias (see for example my comment here). Realistically, though, conflicted reviews will continue, building in a need for additional reviewers to tackle the same ground.

Systematic reviews have found important homes in clinical practice guidelines, health technology assessment, and reimbursement decision-making for both public and private health insurance. But underuse of high quality systematic reviews remains a more significant problem than is addressed here. Even when a systematic review does not identify a strong basis in favor of one option or another, that can still be valuable for decision making - especially in the face of conflicted claims of superiority (and wishful thinking). However, systematic reviews are still not being used enough - especially in shaping subsequent research (see for example Habre C, 2014).

I agree with Ioannidis that collaborations working prospectively to keep a body of evidence up-to-date is an important direction to go - and it is encouraging that the living cumulative network meta-analysis has arrived (Créquit P, 2016). That direction was also highlighted in Page and Moher's accompanying editorial (Page MJ, 2016). However, I'm not so sure how much of a solution this is going to be. The experience of the Cochrane Collaboration suggests this is even harder than it seems. And consider how excited people were back in 1995 at the groundbreaking publication of the protocol for prospective, collaborative meta-analysis of statin trials (Anonymous, 1995) - and the continuing controversy that swirls, tornado-like, around it today (Godlee, 2016).

We need higher standards, and skills in critiquing the claims of systematic reviews and meta-analyses need to spread. Meta-analysis factories are a serious problem. But I still think the most critical issues we face are making systematic reviews quicker and more efficient to do, and to use good ones more effectively and thoroughly than we do now (Chalmers I, 2009, Tsafnat G, 2014).

Disclosure: I work on projects related to systematic reviews at the NCBI (National Center for Biotechnology Information, U.S. National Library of Medicine), including some aspects that relate to the inclusion of systematic reviews in PubMed. I co-authored a paper related to issues raised here several years ago (Bastian H, 2010), and was one of the founding members of the Cochrane Collaboration.

On 2017 Jan 22, Eric Fauman commented:

I know nothing about cow genetics, but I have done some work on the genetics of metabolites in humans, so I was interested to see how the authors derived biological insights from this genetic study. In particular, I was intrigued by the suggestion in the abstract that they found evidence that genes involved in the synthesis of “milk components” are important for lactation persistence.

Unfortunately, the more I studied the paper the more problems I found that call this claim into question.

First off, the Q-Q plot is currently unavailable, but the text mentions there’s only a “slight deviation in the upper right tail”, which could mean there are no true significant signals.

To account for multiple testing, the authors decided to use a genome-wide association p-value cutoff of 0.95/44100 = 2.15e-5 instead of a more defensible 0.05/44100 = 1.1e-6.

Since their initial p-value cutoff yielded a relatively small number of significant SNPs, the authors used a much more lenient p-value cutoff of 5e-4 which presumably is well within the linear portion of the Q-Q plot.

The biggest problem with the enrichment analysis, however, is that they’ve neglected to account for genes drawn from a common locus. Often, paralogs of similar function are proximal in the genome. But typically we assume that a single SNP is affecting the function of only a single gene at a locus. So, for example, a SNP near the APOA4/APOA1/APOC3/APOA5 locus can tag all 4 genes, but it’s unfair to consider that 4 independent indications that “phospholipid efflux”, “reverse cholesterol transport”, “triglyceride homeostasis” and other pathways are “enriched” in this GWAS.

This issue, of overcounting pathways due to gene duplication, affects all their top findings, presumably rendering them non-significant. Besides lipid pathways, this issue also pertains to the “lactation” GO term, which was selected based on the genes GC, HK2, CSN2 and CSN3. GC, CSN2 and CSN3 are all co-located on Chromosome 6.

A perplexing claim in the paper is for the enrichment of the term “lipid metabolic process” (GO:0006629). According to the Ensembl Biomart, 912 Bos taurus genes fall into this category, or about 4% of the bovine protein coding genes (24616 according to Ensembl). So out of their set of 536 genes (flanking SNPs with P < 5e-4) we’d expect about 20 “lipid metabolic process” genes. And yet, this paper reports only 7. This might be significant, but for depletion, not enrichment.

Sample size is of course a huge issue in GWAS. While 3,800 cows is a large number, it appears this trait may require a substantially larger number of animals before it can yield biologically meaningful results.

Question if these lists are adding value here? Yes there are some of each type but does it help the reader to know these are the ones?

More articles to annotate: https://hypothes.is/search?q=tag:%22instructionaldesign%22 Search for other keywords

Week 2 Teaching Notes:

1. Student-led OER research reports

   a. Point to 1-2 example sources

   b. Think through pedagogical choices, issues, Q's

   c. Add viable OER to the Live List

2. The CUNY System

CUNY Mission and History

CUNY Institutional Data

CUNY Maps of NYC

Mapping the Futures of Higher Education Video

Review undergrad class posts about first day in LGBT Short Story class

Assignment for Week 3:

1. Brainstorm together for next questions/directions

2. Look around the CUNY Commons --Write a post with any Commons questions you

   have (please tag "commons")
   

3. Begin building individual or shared Wordpress sites --pick a campus and create its queer profile. What

    classes, instructors, resources, publications, 
    histories, opportunities, needs do you see there?
   

   --Write a post with any Wordpress questions you

    have (tag "wordpress")
   

4. Mapping Queer CUNY group project (use Embed Google Maps plugin or another mapping plugin).

So do Trump's golf excursions and the fact his wife and him have to live separately.

For those of you wishing to know, drzaza means nothing. For those really wishing to know, the word was made up by Nick many moons ago as his ‘handle’ for a plethora of ‘DJ’ mix tapes – a shortened version of the original drzava zaza: drzava being the Serbo-Croat word for ‘the State’ (/nation), and zaza being Nick's schoolbook grafiti tag – thus ‘the state of zaza’. Oh brother.

Interestingly, Diigo allows many of these same functions.

I feel like this particular option on Instagram has become a trend amoungst celebrities. They often tag their location to bring more money to a company or location. It causes "click-bait" so to speak, and has people drawn to this tag who may follow this person on their Instagram.

Click this button to tag accounts

Place before the script tag for fastops.js .

needs 'value' definition, not 'id' definition

needs 'value' definition, not 'id' definition

needs 'type' definition, not 'id' definition

Hi there! When I try to click the link to the article, it doesn't work! I downloaded the article, but then I cannot annotate it with Hypothesis! Help! Thank you!

Greetings wise, experience annotator, sort of like a wizard, eh? How experienced would you say you are in using this tool? What advice would you/will you give to others?

(one might me to add the netnarr tag below, right?)

Well, you are here. You are in the world. You can annotate any thing you select on this web page, or you can reply to someone else's.

Always try to remember to add the netnarr tag below so we can group all annotations across all the digital alchemists.

Is this not like magic? Speaking of which, you can add web links and images, even animated gifs

Just wanted to say NICE JOB re: how you've amended this section & fleshed these details out

Maybe a low-cost iPad will be coming in early 2018

This page can be annotated. If you have a question on something, select the confusing text, and click "Add Annotation," write your comment, and add the tag "110HS18." You will need to create an account with hypothes.is to add annotations.

itt annotálom

Use the tag ENC110236870 to find all of the articles for this course.

https://www.amazon.co.jp/dp/B077Q72KDM/ref=as_li_ss_tl?ie=UTF8&linkCode=sl1&tag=roma08c-22&linkId=f188ea25b50ed3ab451c4c1ad13a22ff

Are we supposed to change directories? These commands do nothing. git hist shows no trail: $ git hist --all

• a97b670 2017-12-11 | Hello uses Greeter (HEAD -> greet) [juancarlucci]
• 6dc342b 2017-12-11 | Added greeter class [juancarlucci]
• 71a5655 2017-12-11 | Added a Rakefile. (master) [juancarlucci]
• 73848f6 2017-12-11 | Moved hello.rb to lib [juancarlucci]
• 00f9e39 2017-12-11 | Add an author/email comment [juancarlucci]
• b4b43ef 2017-12-11 | Added a comment (tag: Ver1) [juancarlucci]
• 87ed367 2017-12-11 | Add a default value (tag: v1-beta) [juancarlucci]
• d8bf589 2017-12-11 | Using ARGV [juancarlucci]
• 3deeb33 2017-12-11 | First Commit (tag: v1) [juancarlucci]

See https://www.mattcutts.com/blog/canonical-link-tag

Second piece of evidence: This piece of evidence gives an example of how a well known social media site was able to handle hate speech in productive way. With handling hate speech the way they did, twitter was able to prove that they were able to handle hate speech on their own without being told or forced to

James Bay lies at the Southernmost tip of the Hudson Bay, bordering both Ontario and Quebec. James Bay was, and still is, the home of many aboriginal communities. Some of these include the Kashechewan, Inuit, and several different communities affiliated with the Cree. James Bay was one of the first occupied areas of Canada, due to its high population of Indigenous people. It is such a popular settlement because of its thriving ecosystem. However, “life in this territory is difficult - the land and waters are frozen for two thirds of year.”1 The Bay is the ending point for thousands of lakes and streams and large rivers such as the St. Lawrence. The James Bay/Hudson Bay watershed recycles one-sixth1 of the world’s fresh water. In 1971, the plans were announced by Hydro-Quebec and the Quebec Government to construct a system of hydroelectric dams. This $5.6 billion3 project would result in destruction of huge amounts of the environment surrounding James Bay. There was immediate outrage by not only the environmentalists, but more importantly the Indigenous people who have called James Bay home for thousands of years. They feared the destruction of their communities. The outrage only grew when word got out that the dams would result in the flooding of over 10,000 square km of land. The Cree has spent 4000-6000 years in this rugged terrain, in which “a complex set of skills were honed to negotiate the particular demands of each season.1 They had spent so long adapting to this way of life, so they had no intent of starting over somewhere else. However, this was also the basis of argument used against the Cree.<br> Claude Peloquin and Fikret Berkes explained that “human groups who interact closely with their environment -- indigenous resource users, hunters, fishers, farmers, and others -- often develop knowledge and practices that are pragmatically adaptive to shifts and changes in the environment.”2 People who were in favor of the project would use this to argue that the Cree and the Inuit were so closely inept with their environment that they should be able to thrive in any environment. Also, they would argue that if they were able to survive for so long in an environment as difficult and complex as the James Bay, then they should have no problem anywhere else. However, the problem was not that the indigenous people were worried that they could not survive anywhere else. The indigenous people themselves knew as well as anyone else that they would have no problem adapting to a new environment, but that was not the point. The point was that they have called this place home for such a long time, so why should they have to pack up and move just because some white people want to make money. After four years of negotiating and fighting for what they believed in, the two sides were finally able to settle. The indigenous people insisted on gaining more control over local governments, a school and health system created just for their own settlements, and a judicial system to protect the people and the environment. They were even able to get Hydro-Quebec to move the site of their first damn, sign an agreement limiting the allowable change of water levels, and a “remedial works system for social and environmental damages.”1 Most importantly, Hydro-Quebec agreed to compensate the indigenous groups affected with immense amounts of money. When all was said and done the Cree and Inuit were paid $225 million over 20 years and the Naskapi received $9 million. Despite the immense payoff, many indigenous people were still unhappy with the deal because they felt that there could be no price tag put on nature. Also, the James Bay Agreement happened two years before Thomas Berger wrote his report. It could be argued that this agreement set a precedent for Berger. By seeing that the natives could simply be paid off, it could have given him the false idea that there really is nothing wrong with taking their land.

Mouth of Attawapiskat River, James Bay Coast, Ontario. 2002.

1Hornig, James F. Social and Environmental Impacts of the James Bay Hydroelectric Project. McGill-Queens University Press, 1999. Page 26.

2Peloquin, Claude, and Fikret Berkes. "Local Knowledge, Subsistence Harvests, and Social–Ecological Complexity in James Bay." Human Ecology37, no. 5 (2009): 533-45. doi:10.1007/s10745-009-9255-0.

3Salisbury, R. A Homeland for the Cree Regional Development in James Bay, 1971-1981. Montreal: McGill-Queens University Press, 2014. January 12, 1986. Accessed November 25, 2017. Page 3, 17.

The importance of military education is quite emphasized in the highlighted portions of the text. To claim that the age for an individual to enter college is the age of "aptness, docility, and emulation of the practices of manhood" is used to further support their belief in the importance of implementing military education into the college's curriculum. The writers also encourages the facilitation and implementation of "tools" into the courses, but does not go into depth as to what the tools are. Nevertheless, the writer of the document again uses his claim on the importance of implementing tools to support his original claim regarding the importance of teaching military education. The state of the militia proposed that "every able-bodied freeman, between the ages of 16 and 50, is [to be] enrolled in the militia" in 1780 and 1781. Though it is merely an assumption, it is believed that the writers of the document strongly suggested the insertion of military education because of how beneficial it could be for students to learn and prepare for the state of the militia as they claim that "such things are soonest learnt, and longest remembered."

-Ardean Kim

http://web.archive.org/web/20110221131205/http://etext.lib.virginia.edu/etcbin/toccer-new2?id=JefVirg.sgm&images=images/modeng&data=/texts/english/modeng/parsed&tag=public&part=9&division=div1

The cost for each dormitory is $350. While reading this, I am confused if this number refers to the cost per student for room and board, or if it is simply the cost to construct each dormitory. (If anybody can clarify that, it would be much appreciated!) But either way, I found this handy website that converts 1817 money to its equivalent in 2017 money. Apparently, $350 back then would be about $6,129.02 nowadays. If this is the price of room and board, then it's actually incredibly consistent. According to UVa's website, our housing expense is $6,270. So if this $350 price tag is truly for room and board, then I find the consistency really astounding!

Recent research on mollusc DNA has found that they do use methylation systems to regulate their expression. This was determined by using bisulfate PCR. The bisulfate creates a tag on a methylated amino acid in the protein sequence, and PCR is a way to generate many different copies of a single strand of DNA. Using different mapping techniques the locations of methyl group were determined. A methyl group added to a DNA structure serves to wrap the DNA tighter around the histone in order to block transcription. AT

iPad deals for Black Friday 2017

Tag size was an important consideration when it came to the assigning of a tag size and type to a specific shark. Smaller sharks were placed with smaller tags because the size and density of the tag could have affected the health of the overall infantile or smaller shark that it was paced in. This measure ensured that results and data for the experiment were viable and the the loves of the sharks were also accounted for and their safety ensured in that area of the study. -Sindy

This is such an attractive component to IDS. While the price tag for learning shouldn't matter, expense I would say is one of the top concerns for students, especially when they are planning to or considering graduate studies. For students on a pre-med, pre-pt, pre-ot, etc. track, IDS allows for a quick, not too expensive, and SMART route for obtaining a well-rounded degree while simultaneously completing all requisite courses prior to applying for grad school. My sister was an Environmental Studies major with a minor in Education who is now pursuing OT school, but has had to complete at least 10 courses before being eligible to apply. IDS would have fit her perfectly.

Will these formulas be given to us on the exam

W. "1 Tag" (statt "ein Tag"): Vv. 3-5 berichten von der Schöpfung der zeitlichen Ordnung, nicht von der Schöpfung der Helligkeit. Funktion der Formel "Es wurde Abend usw." ist hier also nicht nur, davon zu berichten, dass der erste Schöpfungsabschnitt nun abgelaufen ist, sondern ineins damit wird vorgeführt, wie Gott die zeitliche Ordnung ins Sein setzt. Nach der Unterscheidung von Hellem und Finsterem, von Tag und Nacht, muss es 1x Abend und 1x Morgen werden, dann ist die Zeitspanne von "1 Tag" vergangen. Vv. 6ff. berichten dann von der Einsetzung des Raumes.

Vgl. dazu Sasson 1992, S. 191; Steinmann 2002, S. 583f. u.a.

• Sasson, Jack M.: Time...to Begin, in: Michael Fishbane/Emanuel Tov: Sha´arei Talmon: Studies in the Bible, Qumran, and the Ancient Near East, presented to Shemaryahu Talmon. Winona Lake, 1992.
• Steinmann, Andrew E.: אחד as an Ordinal Number and the Meaning of Genesis 1:5, in: JETS 45/4. 2002. S. 577-584.

Mit "dem Hellen" ist wahrscheinlich nicht die "Helligkeit" gemeint (da die Lichtspender ja erst in Vv. 14-19 geschaffen werden), sondern der Tag als Einheit zur Zeitrechnung: Wie im restlichen Kapitel ruft Gott zuerst etwas nur abstrakt Bezeichnetes ins Sein und gibt dem dann einen Namen (z.B. "etwas Schalenförmiges" in Vv. 6-8 für den "Himmel", "Trockenes" in Vv. 9f. für "Erde" usw.; vgl. gut Good 2009, S. 12).

• Good, Edwin M.: Genesis 1-11. Tales of the Earliest World. A New Translation and Essays. Stanford, 2009.

Die Vorstellung einer Welt, die uranfangs im Dunkeln liegt und von Wasser bedeckt ist, ist im ganzen Alten Orient verbreitet:

Bibel

Ps 104,6-8:

*6 Mit der Tiefe deckst du [die Erde] wie mit einem Kleide, / und Wasser standen über den Bergen. 7 Aber vor deinem Schelten flohen sie, / vor deinem Donner fuhren sie dahin. 8 Die Berge gingen hoch hervor, / und die Täler setzten sich herunter zum Ort, / den du ihnen gegründet hast.*

Ägyptisch

Die Weltschöpfung in der Esna-Tradition:

Der Vater der Väter, die Mutter der Mütter, die uranfängliche Wesenheit, die am Anbeginn der Zeit entstand, war nun körperlich in Erscheinung getreten, als sie sich (noch) inmitten des Urgewässers befand, während die Erde (noch) in Finsternis lag, der Tag (noch) in Dunkelheit gehüllt war, bevor (noch) die Erde (aus dem Urgewässer) hervorgetreten war und bevor es Vegetation gab. (Üs.: TUAT III/5, S. 1079)

Sargtext 80 [Die Rede ist von der Schöpfung der acht Götter, die dem Gott Schu bei der Schöpfung helfen]:

Oh, ihr acht Unendlichen - unendliche Zahl Unendlicher! - / die ihr den Himmel mit euren Armen umfasst, / die ihr zusammenzieht Himmel und Horizont Gebs! / Schu gab euch Geburt / aus der Flut, aus den Wassern, / aus der Verlorenheit, aus der Dunkelheit... (Üs. nach COS 1.8)

Babylonisch

Enuma Elisch:

Als oben der Himmel noch nicht existierte / und unten die Erde noch nicht entstanden war - / gab es Apsu, den ersten, ihren Erzeuger, / und Schöpferin Tiamat, die sie alle gebar; / sie hatten ihre Wasser miteinander vermischt, / ehe sich Weideland verband und Röhricht zu finden war... (Üs.: TUAT III/4, S. 569)

Hethitisch:

Telipinu und die Tochter des Meeres:

Früher, als das große M[eer der Alleinherrscher war - als aber] Himmel, Erde (und) Menschhe[it geschaffen wurden,] (da) wurde es streitsüchtig und holte [den Sonnengott des Himmels] herunter und [hielt] ihn [versteckt]. Dies [hatte] im Lande schlimme [Folgen], (da) Dunkelheit hereinbrach. Das Me[er tobte], (und) niemand konnte ihm widerstehen. (Üs.: TUAT III/4, S. 811)

Sumerisch

Kosmogonie aus Nibru

An, der Herr, erhellte den Himmel, die Erde war dunkel, / in die Unterwelt wurde nicht geschaut, / aus der Tiefe wurde noch kein Wasser geschöpft, / nichts wurde geschaffen... (Üs.: TUAT III/3, S. 353)

Die Vorstellung einer Welt, die uranfangs im Dunkeln liegt und von Wasser bedeckt ist, ist im ganzen Alten Orient verbreitet:

Bibel

Ps 104,6-8:

*6 Mit der Tiefe deckst du [die Erde] wie mit einem Kleide, / und Wasser standen über den Bergen. 7 Aber vor deinem Schelten flohen sie, / vor deinem Donner fuhren sie dahin. 8 Die Berge gingen hoch hervor, / und die Täler setzten sich herunter zum Ort, / den du ihnen gegründet hast.*

Ägyptisch

Die Weltschöpfung in der Esna-Tradition:

Der Vater der Väter, die Mutter der Mütter, die uranfängliche Wesenheit, die am Anbeginn der Zeit entstand, war nun körperlich in Erscheinung getreten, als sie sich (noch) inmitten des Urgewässers befand, während die Erde (noch) in Finsternis lag, der Tag (noch) in Dunkelheit gehüllt war, bevor (noch) die Erde (aus dem Urgewässer) hervorgetreten war und bevor es Vegetation gab. (Üs.: TUAT III/5, S. 1079)

Sargtext 80 [Die Rede ist von der Schöpfung der acht Götter, die dem Gott Schu bei der Schöpfung helfen]:

Oh, ihr acht Unendlichen - unendliche Zahl Unendlicher! - / die ihr den Himmel mit euren Armen umfasst, / die ihr zusammenzieht Himmel und Horizont Gebs! / Schu gab euch Geburt / aus der Flut, aus den Wassern, / aus der Verlorenheit, aus der Dunkelheit... (Üs. nach COS 1.8)

Babylonisch

Enuma Elisch:

Als oben der Himmel noch nicht existierte / und unten die Erde noch nicht entstanden war - / gab es Apsu, den ersten, ihren Erzeuger, / und Schöpferin Tiamat, die sie alle gebar; / sie hatten ihre Wasser miteinander vermischt, / ehe sich Weideland verband und Röhricht zu finden war... (Üs.: TUAT III/4, S. 569)

Hethitisch:

Telipinu und die Tochter des Meeres:

Früher, als das große M[eer der Alleinherrscher war - als aber] Himmel, Erde (und) Menschhe[it geschaffen wurden,] (da) wurde es streitsüchtig und holte [den Sonnengott des Himmels] herunter und [hielt] ihn [versteckt]. Dies [hatte] im Lande schlimme [Folgen], (da) Dunkelheit hereinbrach. Das Me[er tobte], (und) niemand konnte ihm widerstehen. (Üs.: TUAT III/4, S. 811)

Sumerisch

Kosmogonie aus Nibru

An, der Herr, erhellte den Himmel, die Erde war dunkel, / in die Unterwelt wurde nicht geschaut, / aus der Tiefe wurde noch kein Wasser geschöpft, / nichts wurde geschaffen... (Üs.: TUAT III/3, S. 353)

Mit "dem Hellen" ist wahrscheinlich nicht die "Helligkeit" gemeint (da die Lichtspender ja erst in Vv. 14-19 geschaffen werden), sondern der Tag als Einheit zur Zeitrechnung: Wie im restlichen Kapitel ruft Gott zuerst etwas nur abstrakt Bezeichnetes ins Sein und gibt dem dann einen Namen (z.B. "etwas Schalenförmiges" in Vv. 6-8 für den "Himmel", "Trockenes" in Vv. 9f. für "Erde" usw.; vgl. gut Good 2009, S. 12).

• Good, Edwin M.: Genesis 1-11. Tales of the Earliest World. A New Translation and Essays. Stanford, 2009.

W. "1 Tag" (statt "ein Tag"): Vv. 3-5 berichten von der Schöpfung der zeitlichen Ordnung, nicht von der Schöpfung der Helligkeit. Funktion der Formel "Es wurde Abend usw." ist hier also nicht nur, davon zu berichten, dass der erste Schöpfungsabschnitt nun abgelaufen ist, sondern ineins damit wird vorgeführt, wie Gott die zeitliche Ordnung ins Sein setzt. Nach der Unterscheidung von Hellem und Finsterem, von Tag und Nacht, muss es 1x Abend und 1x Morgen werden, dann ist die Zeitspanne von "1 Tag" vergangen. Vv. 6ff. berichten dann von der Einsetzung des Raumes.

Vgl. dazu Sasson 1992, S. 191; Steinmann 2002, S. 583f. u.a.

• Sasson, Jack M.: Time...to Begin, in: Michael Fishbane/Emanuel Tov: Sha´arei Talmon: Studies in the Bible, Qumran, and the Ancient Near East, presented to Shemaryahu Talmon. Winona Lake, 1992.
• Steinmann, Andrew E.: אחד as an Ordinal Number and the Meaning of Genesis 1:5, in: JETS 45/4. 2002. S. 577-584.

W. "1 Tag" (statt "ein Tag"): Vv. 3-5 berichten von der Schöpfung der zeitlichen Ordnung, nicht von der Schöpfung der Helligkeit. Funktion der Formel "Es wurde Abend usw." ist hier also nicht nur, davon zu berichten, dass der erste Schöpfungsabschnitt nun abgelaufen ist, sondern ineins damit wird vorgeführt, wie Gott die zeitliche Ordnung ins Sein setzt. Nach der Unterscheidung von Hellem und Finsterem, von Tag und Nacht, muss es 1x Abend und 1x Morgen werden, dann ist die Zeitspanne von "1 Tag" vergangen. Vv. 6ff. berichten dann von der Einsetzung des Raumes.

Vgl. dazu Sasson 1992, S. 191; Steinmann 2002, S. 583f. u.a.

• Sasson, Jack M.: Time...to Begin, in: Michael Fishbane/Emanuel Tov: Sha´arei Talmon: Studies in the Bible, Qumran, and the Ancient Near East, presented to Shemaryahu Talmon. Winona Lake, 1992.
• Steinmann, Andrew E.: אחד as an Ordinal Number and the Meaning of Genesis 1:5, in: JETS 45/4. 2002. S. 577-584.

Mit "dem Hellen" ist wahrscheinlich nicht die "Helligkeit" gemeint (da die Lichtspender ja erst in Vv. 14-19 geschaffen werden), sondern der Tag als Einheit zur Zeitrechnung: Wie im restlichen Kapitel ruft Gott zuerst etwas nur abstrakt Bezeichnetes ins Sein und gibt dem dann einen Namen (z.B. "etwas Schalenförmiges" in Vv. 6-8 für den "Himmel", "Trockenes" in Vv. 9f. für "Erde" usw.; vgl. gut Good 2009, S. 12).

• Good, Edwin M.: Genesis 1-11. Tales of the Earliest World. A New Translation and Essays. Stanford, 2009.

Die Vorstellung einer Welt, die uranfangs im Dunkeln liegt und von Wasser bedeckt ist, ist im ganzen Alten Orient verbreitet:

Bibel

Ps 104,6-8:

*6 Mit der Tiefe deckst du [die Erde] wie mit einem Kleide, / und Wasser standen über den Bergen. 7 Aber vor deinem Schelten flohen sie, / vor deinem Donner fuhren sie dahin. 8 Die Berge gingen hoch hervor, / und die Täler setzten sich herunter zum Ort, / den du ihnen gegründet hast.*

Ägyptisch

Die Weltschöpfung in der Esna-Tradition:

Der Vater der Väter, die Mutter der Mütter, die uranfängliche Wesenheit, die am Anbeginn der Zeit entstand, war nun körperlich in Erscheinung getreten, als sie sich (noch) inmitten des Urgewässers befand, während die Erde (noch) in Finsternis lag, der Tag (noch) in Dunkelheit gehüllt war, bevor (noch) die Erde (aus dem Urgewässer) hervorgetreten war und bevor es Vegetation gab. (Üs.: TUAT III/5, S. 1079)

Sargtext 80 [Die Rede ist von der Schöpfung der acht Götter, die dem Gott Schu bei der Schöpfung helfen]:

Oh, ihr acht Unendlichen - unendliche Zahl Unendlicher! - / die ihr den Himmel mit euren Armen umfasst, / die ihr zusammenzieht Himmel und Horizont Gebs! / Schu gab euch Geburt / aus der Flut, aus den Wassern, / aus der Verlorenheit, aus der Dunkelheit... (Üs. nach COS 1.8)

Babylonisch

Enuma Elisch:

Als oben der Himmel noch nicht existierte / und unten die Erde noch nicht entstanden war - / gab es Apsu, den ersten, ihren Erzeuger, / und Schöpferin Tiamat, die sie alle gebar; / sie hatten ihre Wasser miteinander vermischt, / ehe sich Weideland verband und Röhricht zu finden war... (Üs.: TUAT III/4, S. 569)

Hethitisch:

Telipinu und die Tochter des Meeres:

Früher, als das große M[eer der Alleinherrscher war - als aber] Himmel, Erde (und) Menschhe[it geschaffen wurden,] (da) wurde es streitsüchtig und holte [den Sonnengott des Himmels] herunter und [hielt] ihn [versteckt]. Dies [hatte] im Lande schlimme [Folgen], (da) Dunkelheit hereinbrach. Das Me[er tobte], (und) niemand konnte ihm widerstehen. (Üs.: TUAT III/4, S. 811)

Sumerisch

Kosmogonie aus Nibru

An, der Herr, erhellte den Himmel, die Erde war dunkel, / in die Unterwelt wurde nicht geschaut, / aus der Tiefe wurde noch kein Wasser geschöpft, / nichts wurde geschaffen... (Üs.: TUAT III/3, S. 353)

Die Vorstellung einer Welt, die uranfangs im Dunkeln liegt und von Wasser bedeckt ist, ist im ganzen Alten Orient verbreitet:

Bibel

Ps 104,6-8:

*6 Mit der Tiefe deckst du [die Erde] wie mit einem Kleide, / und Wasser standen über den Bergen. 7 Aber vor deinem Schelten flohen sie, / vor deinem Donner fuhren sie dahin. 8 Die Berge gingen hoch hervor, / und die Täler setzten sich herunter zum Ort, / den du ihnen gegründet hast.*

Ägyptisch

Die Weltschöpfung in der Esna-Tradition:

Der Vater der Väter, die Mutter der Mütter, die uranfängliche Wesenheit, die am Anbeginn der Zeit entstand, war nun körperlich in Erscheinung getreten, als sie sich (noch) inmitten des Urgewässers befand, während die Erde (noch) in Finsternis lag, der Tag (noch) in Dunkelheit gehüllt war, bevor (noch) die Erde (aus dem Urgewässer) hervorgetreten war und bevor es Vegetation gab. (Üs.: TUAT III/5, S. 1079)

Sargtext 80 [Die Rede ist von der Schöpfung der acht Götter, die dem Gott Schu bei der Schöpfung helfen]:

Oh, ihr acht Unendlichen - unendliche Zahl Unendlicher! - / die ihr den Himmel mit euren Armen umfasst, / die ihr zusammenzieht Himmel und Horizont Gebs! / Schu gab euch Geburt / aus der Flut, aus den Wassern, / aus der Verlorenheit, aus der Dunkelheit... (Üs. nach COS 1.8)

Babylonisch

Enuma Elisch:

Als oben der Himmel noch nicht existierte / und unten die Erde noch nicht entstanden war - / gab es Apsu, den ersten, ihren Erzeuger, / und Schöpferin Tiamat, die sie alle gebar; / sie hatten ihre Wasser miteinander vermischt, / ehe sich Weideland verband und Röhricht zu finden war... (Üs.: TUAT III/4, S. 569)

Hethitisch:

Telipinu und die Tochter des Meeres:

Früher, als das große M[eer der Alleinherrscher war - als aber] Himmel, Erde (und) Menschhe[it geschaffen wurden,] (da) wurde es streitsüchtig und holte [den Sonnengott des Himmels] herunter und [hielt] ihn [versteckt]. Dies [hatte] im Lande schlimme [Folgen], (da) Dunkelheit hereinbrach. Das Me[er tobte], (und) niemand konnte ihm widerstehen. (Üs.: TUAT III/4, S. 811)

Sumerisch

Kosmogonie aus Nibru

An, der Herr, erhellte den Himmel, die Erde war dunkel, / in die Unterwelt wurde nicht geschaut, / aus der Tiefe wurde noch kein Wasser geschöpft, / nichts wurde geschaffen... (Üs.: TUAT III/3, S. 353)

Eine alte jüd. Auslegungstradition: Das Wort für "ruhen" lässt sich auch mit "feiern" übersetzen. Anders als die anderen sechs Tage wird der siebte Tag nicht vollendet: Er dauert fort, und nach wie vor ist Gott am feiern und sollen auch wir dies tun.

Eine schöne Eigentümlichkeit dieses Abschnitts ist sein Variationsreichtum und seine Betonung der Fünfzahl. Die "Kriecher" etwa - die Reptilien also - werden in fünf Versen mit fünf verschiedenen Bezeichnungen versehen:

• V. 24: "Kriecher"
• V. 25: "Alle Bodenkriecher"
• V. 26: "Alle Kriecher, die auf Erden kriechen"
• V. 28: "Alle Lebewesen, die auf Erden kriechen"
• V. 30: "Alle Kriecher auf Erden, die Leben in sich haben".

Ein anderes Beispiel ist die Reihenfolge der drei Landtierfamilien, die drei Mal in Folge variiert und im letzten Vers zum Fünfschritt erweitert wird:

• V. 24: Vieh - Kriecher - wilde Tiere
• V. 25: Wilde Tiere - Vieh - Kriecher
• V. 26: [Fische - Vögel -] Vieh - wilde Tiere - Kriecher

Dazu kommt allgemein die starke Häufung der Betonung der Vielfalt; das "verschiedenste Arten von..." etwa fällt fünf Mal allein in Vv. 24f.

Ein Effekt dieser beiden Stileigentümlichkeiten ist sicher die Hervorhebung des Menschen unter allen Landtieren. So vieles Verschiedenes hat Gott geschaffen, und doch ragt unter den verschiedensten Arten von Schöpfungswesen an den ersten 5 Tagen jenes letzte des 6. Tages besonders hervor: Der Mensch, der Stellvertreter Gottes; die "Krone der Schöpfung", zu der ersten fünf Schöpfungstage hingeführt haben.

W. "1 Tag" (statt "ein Tag"): Vv. 3-5 berichten von der Schöpfung der zeitlichen Ordnung, nicht von der Schöpfung der Helligkeit. Funktion der Formel "Es wurde Abend usw." ist hier also nicht nur, davon zu berichten, dass der erste Schöpfungsabschnitt nun abgelaufen ist, sondern ineins damit wird vorgeführt, wie Gott die zeitliche Ordnung ins Sein setzt. Nach der Unterscheidung von Hellem und Finsterem, von Tag und Nacht, muss es 1x Abend und 1x Morgen werden, dann ist die Zeitspanne von "1 Tag" vergangen. Vv. 6ff. berichten dann von der Einsetzung des Raumes.

Vgl. dazu Sasson 1992, S. 191; Steinmann 2002, S. 583f. u.a.

• Sasson, Jack M.: Time...to Begin, in: Michael Fishbane/Emanuel Tov: Sha´arei Talmon: Studies in the Bible, Qumran, and the Ancient Near East, presented to Shemaryahu Talmon. Winona Lake, 1992.
• Steinmann, Andrew E.: אחד as an Ordinal Number and the Meaning of Genesis 1:5, in: JETS 45/4. 2002. S. 577-584.

Mit "dem Hellen" ist wahrscheinlich nicht die "Helligkeit" gemeint (da die Lichtspender ja erst in Vv. 14-19 geschaffen werden), sondern der Tag als Einheit zur Zeitrechnung: Wie im restlichen Kapitel ruft Gott zuerst etwas nur abstrakt Bezeichnetes ins Sein und gibt dem dann einen Namen (z.B. "etwas Schalenförmiges" in Vv. 6-8 für den "Himmel", "Trockenes" in Vv. 9f. für "Erde" usw.; vgl. gut Good 2009, S. 12).

• Good, Edwin M.: Genesis 1-11. Tales of the Earliest World. A New Translation and Essays. Stanford, 2009.

Let me add another piece of information to this tag

You probably don't have to go this deep, especially if you're looking tocut words

Not much info in this sentence

Clutter, can be removed

Clutter

Examples/quotes would be handy here!

I actually rather liked the structure you had where you started each paragraph with an era of Pound's poetry, and might recommend maintaining it. I would try to move this to the top of the paragraph; you can decide if you want to remove the information before or find a way to incorporate it into previous paragraphs

You can tie this into the previous sentence to cut words

" . . . to Harvard, which formalized his separation with his wife."

This is an interesting side path, but you don't really go into what effects these influences had on his poetry. I would go deeper with this or cut it entirely.

I would say the same thing: perhaps go deeper (give a quote from Pound, maybe) and explain this relationship more, or cut it to keep your length down.

The verb "reach" is a little vague.

We don't know that she's insane at this point, so a little exposition might be helpful

This detail is a little tangential and not expanded upon very much. If you're going to include it, I would delve into it further and detail their interactions, but otherwise I would cut it for brevity's sake.

Titles in quotation marks; I'd say this for the other ones too, but will only mark it here to avoid cluttering up your page

You can cut this, as the rest of the sentence restates this

This a bold claim that you could supplement with some details/evidence in order to persuade the reader that it's actually true:

• How do we know he was influential? Perhaps a quote from a contemporary or critic would work well here
• What did he influence (which movements, groups, etc.)?

While you do establish some of these things later on in your paper, it'd be a stronger opening if you could immediately hook the reader and persuade them that Eliot matters. Admittedly, he is well-known enough that his name might speak for itself, but you don't want to rely on that; you want your writing to reflect it.

I wonder if this is a useful tag?

If you have room, I would just suggest adding how/why he returned to Paris because the bio goes straight from his refuge in Spain to him dying in his Paris home. Something as simple as "Picabia eventually returned to his home country..." would help chronologically.

"beginning" instead of "causing" perhaps

"a very new and abstract concept" may work here as well?

"not being a household name" would suffice

obsessed is a strong word, it works but if you use this word I as a reader would want you to elaborate further on how he was obsessed with it (versus perhaps fascinated, for example)

"and" would probably work better here

America / the United States

I would suggest using "beginning with" or "starting with" rather than "starting during" ; it just makes the sentence flow better.

Curator: @Jmenke

Resource used:

(MBL International Cat# M185-7, RRID:AB_2687989)

SciCrunch record: RRID:AB_2687989

Alternate resolvers: SciCrunch xml N2T identifiers.org

What is this?

Curator: @Jmenke

Resource used:

(Cell Signaling Technology Cat# 13202, RRID:AB_2687461)

SciCrunch record: RRID:AB_2687461

Alternate resolvers: SciCrunch xml N2T identifiers.org

What is this?

Curator: @Jmenke

Resource used:

(Sigma-Aldrich Cat# H9658, RRID:AB_260092)

SciCrunch record: RRID:AB_260092

Alternate resolvers: SciCrunch xml N2T identifiers.org

What is this?

Curator: @chewbeccax

Resource used:

(Cell Signaling Technology Cat# 2368, RRID:AB_2217020)

SciCrunch record: RRID:AB_2217020

Alternate resolvers: SciCrunch xml N2T identifiers.org

What is this?

slightly awkward wording here

possibly identify who this woman is - she sort of just appears out of left field.

clarify - is this a column?

possibly rephrase along the lines of "Flanner began what would be her lifelong career as the Paris correspondent for The New Yorker", etc.

"which had just been created"

perhaps include some context as to why the poor reviews of Flanner's book led her to be cold toward Mina Loy. Without any details it leaves the reader sort of confused.

"where they talked [about]"

"and settled in Paris in 1922,"

This wording is very, very awkward; perhaps the two "lived as lesbians together" (were they out in Paris or not? This may be a pertinent detail to include).

"for whom Janet left Rehm" - also, while we're on this annotation, I wanted to point out it may be wise to stick to either "Janet" or "Flanner" when writing the biography, just to be consistent. I would go with "Flanner" but ultimately it's up to you.

I would possibly change this wording to something along the lines of "a decision which introduced"

I don't believe you need a hyphen here.

"in"

Skal det ikke være an=(ane1)e1+(ane2)e2+...+(an*en)en

Curator: @chewbeccax

Curator note: No RRID tag.

Resource used:

RRID:IMSR_JAX:000664

SciCrunch record: RRID:IMSR_JAX:000664

Alternate resolvers: SciCrunch xml N2T identifiers.org

What is this?

Curator: @chewbeccax

Curator note: Did not put in "RRID" tag - scibot couldn't pick up

Resource used:

(Thermo Fisher Scientific Cat# A21428, RRID:AB_10561552)

SciCrunch record: RRID:AB_10561552

Alternate resolvers: SciCrunch xml N2T identifiers.org

What is this?

Curator: @gabimpine

Curator note: likely the right tag

Resource used:

(UCSC Genome Browser, RRID:SCR_005780)

SciCrunch record: RRID:SCR_005780

Alternate resolvers: SciCrunch xml N2T identifiers.org

What is this?

Curator: @chewbeccax

Resource used:

(Qiagen Cat# 34660, RRID:AB_2619735)

SciCrunch record: RRID:AB_2619735

Alternate resolvers: SciCrunch xml N2T identifiers.org

What is this?

Curator: @chewbeccax

Resource used:

(Molecular Probes Cat# A-11120, RRID:AB_221568)

SciCrunch record: RRID:AB_221568

Alternate resolvers: SciCrunch xml N2T identifiers.org

What is this?

Curator: @chewbeccax

Resource used:

(Thermo Fisher Scientific Cat# MA5-15256, RRID:AB_10979281)

SciCrunch record: RRID:AB_10979281

Alternate resolvers: SciCrunch xml N2T identifiers.org

What is this?

Curator: @gabimpine

Resource used:

(Cell Signaling Technology Cat# 2276, RRID:AB_331783)

SciCrunch record: RRID:AB_331783

Alternate resolvers: SciCrunch xml N2T identifiers.org

What is this?

Curator: @jcabotaj

Resource used:

(Thermo Fisher Scientific Cat# 372900, RRID:AB_10104413)

SciCrunch record: RRID:AB_10104413

Alternate resolvers: SciCrunch xml N2T identifiers.org

What is this?

Curator: @gabimpine

Resource used:

(Thermo Fisher Scientific Cat# 451098, RRID:AB_2532221)

SciCrunch record: RRID:AB_2532221

Alternate resolvers: SciCrunch xml N2T identifiers.org

What is this?

This doesn't necessarily mean that the atoms themselves are positive or negative, right? This is only related to their electronegativity (0-4)? So, A could be X=2.2 and B could be X=2.4 and A would be positive because it has a lower electronegativity?

Might it be worth mentioning here that Levy became Loy's son-in-law?

Who credits Bunuel with this praise?

Who described them this way?

delete?

With what specifically did they take issue in Bunuel's film?

seek

I think you could just choose one of these adjectives.

Could you be a little more specific here? With what did Bunuel take issue in regards to this social structure?

This wording is a little awkward.

So basically all the discussions we have had within Hypothesis about rights to write over web pages will be had, but this time applied to the real world.

The bio has a lot of great information, especially on Mina Loy. However, you could use some reorganization. There is information at the end that belongs earlier in the biography, and it's hard to see the focus and structure of the biography. You have a really great start here, and I can see that you've done a fair amount of research!

Good!

You already talked about Expectation. Why is this so late in the bio?

You need this information way earlier

This seems out of place. Revise this sentence

Their relationship or his mental state? Confusing

Connect this back to the painting in the novel

what do you mean by intimate?

I would separate the sentence here.

I would say Oelze since you refer to him by his last name elsewhere

I would revise this sentence

paintings

explain this quote after you use it. I'm not quite sure what you're trying to say here

add a comma

cut

Which characters? You also already said this.

or you could say soon after meeting Oelze

I'm not sure what you mean by this

but you have three characters listed here. I would revise this sentence

add a comma after 1970's

I think that they show and express rather than represent.

What was he before?

I would definitely include his DOB and DOD in the biography

I suggest you talk about the different of before and after.

you can simply this to just "released from being"

This is awkward

started what?

I would be careful to not just list his major works, but to talk about trends in his work, or in his life. Right now, parts of this read like a list of his major works. I suggest being careful with this, and using the works as examples, rather than the focus. That way it will be the works in context of his life, rather than the other way around.

good

how specifically? Use some more details in this semester

Good details!

Where was he born? Did he grow up in a family?

I would expand more on his legacy. What is he remembered for? If his style is a focus, consider moving some of the earlier details here to add more to this.

I would consider revising these sentences. Up to this point you've included both simple and complex sentences, and this paragraph has simple sentences.

I think you can definitely expand this paragraph. This is one of the most important pieces of the biography, so you should consider adding more details an information into this.

more details

give more details.

dates?

keep in chronological order

why is this out of order?

comma inside quotation mark

enjoyed. Keep the past tense

what kind of injury?

the unity

comma inside the quotation mark

Great start to the biography! Looks fantastic

Place the period inside the quotation mark

Looks great!! No grammar issues, no big problems. You use a lot of semi colons to connect together sentences, maybe think about removing some of them just because you have a lot of very long sentences. But it's up to you!

add a space before it

I think you don't have to say this

I think you need a comma after direction

the initial or an initial?

Good!

Maybe break this sentence up, it's a little long

Although I think this information is fascinating, I'd consider cutting this to meet the word count simply because this info would be more crucial if the project were about her and not Loy.

extra on, maybe?

Really well-phrased!

add ,

I feel like these are all saying something about her character; when you shorten your bio, perhaps these could be included in one brief, single paragraph

???

This is a lot of important information shoved into one sentence; maybe revise.

specify country because not everyone will know that this is, I am assuming Italy, because Florence is in Italy.

Take a second look at this sentence; you should revise this.

what kind of debut? social? authorial?