text:
PubMed Commons Comments
The NCBI's PubMed Commons commenting was stopped March 2018 and links to PubMed Abstracts were cut. Although we did not know it, we contributors to PMC from 2013-2018 had been guinea pigs. It had been an "experiment." The comments were stored in NCBI Excel files in a form that was difficult to access. Some comments stored in The Wayback Machine were retrievable. Comment files were also made available by the Hypothesis website, and the PubPeer website.
As a back up, I also placed my comments here. I begin with my comments made later than Sept 7 2016 and ending Feb 9 2018 and there are links to the Wayback site for earlier comments. My list is not entirely complete. To illustrate the issue, I begin with a posting I made in The Scholarly Kitchen Blog on 7 March 2018.
THE PUBMED COMMONS PEER REVIEW INITIATIVE
The pre-publication "peer review initiatives," which Tim Vines cogently deplores as "a curious blindness," prompts similar thoughts concerning a notable post-publication peer review initiative that the NCBI began in 2013. Whereas prepublication review provides some index of quality, a more exacting review is made after publication by readers who are influenced by, and may act upon, the information they have obtained. Citations provide one index of this. The other is post-publication peer review as provided by PubMed Commons. Remarkably, the results of the latter, may feed back into the pre-publication peer review process .
Those charged with reviewing a new paper, or grant application, or even a Nobel prize suggestion, are confronted with an author's list of publications. Pasting each title into PubMed Commons, one sees an abstract of the publication, sometimes accompanied by the freely-given post-publication peer-review comments.
Often meant to be constructive, and monitored for politeness by PubMed staff, it seems likely that sometimes authors, editors, the original pre-publication peer reviewers, and even publishing houses, were embarrassed by the comments. Flaws, sometimes of a degree that Leonid Schneider so rightly deplores in his webpages, emerged, not only in works of authors world-wide, but also in the works of NCBI staff, which includes expatriates from Russia and other countries.
Sadly, the NCBI have now declared PubMed Commons an "experiment." An experiment that failed. The criterion was the number of comments received, not their quality. Despite important feedback when its intention to terminate was announced, the NCBI's post-publication peer-review ended last week, and with it, a source of invaluable assistance to the pre-publication, (and pre-Nobel), peer-review process!
PubMed Commons Comment on "Antigen Identification for Orphan T Cell Receptors Expressed on Tumor-Infiltrating Lymphocytes" Gee et al. 2018 Cell 172:549-563. [7 Feb 2018]
ORPHAN T-CELL RECEPTORS RECOGNIZE UNMUTATED SELF ANTIGENS
This study reveals the great power of the yeast-library approach in displaying peptide-MHC complexes that can be recognized by T-cells that have infiltrated tumors (TILs). As stated (1), the approach "requires no a priori knowledge regarding the nature of these antigens," and "is an unbiased interrogation of TCR specificities." While conceding that "we cannot conclude that any TIL TCR is exclusively present within tumor due to limited sampling of healthy tissue," the authors express surprise that, of the four receptors identified, three recognized unmutated self-antigens. It can be noted, however, that this had been predicted on theoretical grounds two decades earlier (2). While the underlying theory received subsequent modification (3), and may indeed by entirely incorrect, the correlation of this intriguing experimental observation with theory may be worth noting.
1.Gee et al. (2018) Antigen identification for orphan T cell receptors expressed on tumor-infiltrating lymphocytes" Cell 172:549-563. <PMID:29275860>
2.Forsdyke DR (1999) Heat shock proteins as mediators of aggregation-induced "danger" signals: implications of the slow evolutionary fine-tuning of sequences for the antigenicity of cancer cells. Cell Stress & Chaperones 4:205-210. < PMID:10590834>
3.Forsdyke DR (2001) Adaptive value of polymorphism in intracellular self/not-self discrimination? Journal of Theoretical Biology 210:425-434. <PMID:11403563>
PubMed Comment on "An Evolutionary Perspective on the Systems of Adaptive Immunity" by Muller V, Boer RJ de, Bonhoeffer S, Szathmary E (2018) Biol Rev 93: 505-528 <PMID:28745003> [20 Jan 2018]
PATHOGEN COEVOLUTION AND THE ANTIGENIC UNIVERSE
The distinction between selective and instructive (Lamarckian) systems of immunity (1) – originating with Paul Ehrlich – was clearly set out in 1957 by Talmage (2) who, with Burnet, can be considered a "father of clonal selection theory" (3, 4). Its historical omissions aside, this bold attempt to place the evolution of immune systems in a broad context raises other concerns.
Although mentioning "the complex adaptation of the immune repertoire to the antigenic environment," and the need "continuously to acquire and store open-ended information about the antigenic environment," the coevolution of that antigenic environment (e.g. the coevolution of pathogens) does not seem to have been considered.
While the authors agree with Burnet that "distinguishing tumours from normal self is likely to be the most challenging task for Darwinian immunity," it is not recognized that the most successful pathogens are those that, through mutation, can come close to self. Whereas tumours represent mutations away from self, successful pathogens represent mutations towards self (by means of which they seek to exploit 'holes' in immune repertoires; 5). In both circumstances, this greatly simplifies the evolutionary task of a host. It does not have to depend on "the open-ended nature of the receptor repertoire." It does not have to "constitutes a system of 'unlimited heredity' within the immune system." It does not have to "be broad enough to recognize the 'potential universe of antigens'." The scope of its task is greatly reduced.
As long ago proposed (6), and increasingly recognized (7, 8), it would be evolutionarily advantageous for organisms to focus their immune cell receptors on 'near self' antigenic specificities, rather than to attempt to anticipate the entire universe of antigens. Organisms achieve this, not through negative, but through positive selection of their immune repertoires. From the outset, organisms and their pathogens have coevolved and it would seem incorrect to suppose for the immune system that positive selection "could only be added at advanced stages of its evolution" (9). It is fundamental to immune system evolution.
1. Muller V, Boer RJ de, Bonhoeffer S, Szathmary E (2018) Biol Rev 93: 505-528 <PMID:28745003>
2. Talmage DW (1957) Allergy and immunology. Ann Rev Med 8:239-256 <PMID:13425332>
3. Forsdyke DR (1996) The origins of the clonal selection theory of immunity. FASEB J 9:164-166. <PMID:7781918>
4. Lederberg J (2002) Instructive selection and immunological theory. Immunol Rev 185:50-53. <PMID:12190921>
5. Calis JJA, de Boer RJ, Kesmir C (2012) Degenerate T-cell recognition of peptides on MHC molecules creates large holes in the T-cell repertoire. PLoS Comput Biol 8: e1002412.<PMID:22396638>
6. Forsdyke DR (1975) Further implications of a theory of immunity. J Theoret Biol 52:l87-l98.<PMID:50501>
7. Vrisekoop N, Monteiro JP, Mandl JN, Germain RN (2014) Revisiting thymic positive selection and the mature T cell repertoire for antigen. Immunity 41: 181-190.<PMID:25148022>
8. Marrack P. et al. (2017) The somatically generated portion of T cell receptor CDR3alpha contributes to the MHC allele specificity of the T cell receptor. eLife 6: e30918.<PMID:29148973>
9.Forsdyke DR (2016) Evolutionary Bioinformatics. 3rd Edition. Springer, New York.
This provoked the following response:
Viktor Müller2018 Jan 26 7:13 p.m. (yesterday)
While it is true that there is considerable overlap in the recognition of self and (possibly pathogenic) non-self epitopes (Calis et al [1] estimated an overlap of around one third for HLA class I alleles), this is likely to make the job of the immune system harder, rather than easier. The overlapping peptides tend to be non-immunogenic, indicating tolerance, and the immune system needs to be able to target epitopes that are distinguishable from self peptides even with the degenerate recognition of T cell receptors [1]. Furthermore, even if the recognition task was indeed reduced to self and similar peptides, this would still vastly exceed the capacity of a fixed germline-encoded receptor repertoire. The number of distinct potential epitopes (for HLA class I) is of the order of magnitude 107 in humans [2] and in mice [3]; this exceeds the maximum number of germline immune receptors found in any species by several orders of magnitude.
We still maintain that "Distinguishing tumours from normal self is likely to be the most challenging task for Darwinian immunity that could only be added at advanced stages of its evolution" [4], but have never claimed the same for positive selection. Amphioxus has proto-MHC, and positive selection might indeed be an ancient characteristic of (vertebrate) Darwinian immunity. It will be instructive to elucidate whether and how the divergent adaptive system of jawless fish handles positive selection, or anything analogous to MHC restriction in general.
Finally, we note that the origin of vertebrate adaptive immunity is a notoriously difficult problem. We certainly do not know the whole truth about the complex events that took place more than half a billion years ago -- but we hope that, by surveying the most recent evidence, we have taken a small step in the right direction.
[1] Calis JJA, de Boer RJ, Keşmir C (2012) Degenerate T-cell Recognition of Peptides on MHC Molecules Creates Large Holes in the T-cell Repertoire. PLoS Comput Biol 8(3): e1002412. https://doi.org/10.1371/journal.pcbi.1002412
[2] Burroughs, N.J., de Boer, R.J. & Keşmir, C. Immunogenetics (2004) 56: 311. https://doi.org/10.1007/s00251-004-0691-0
[3] Müller, V. & Bonhoeffer, S. (2003). Quantitative constraints on the scope of negative selection. Trends Immunol 24, 132-5. https://doi.org/10.1016/S1471-4906(03)00028-0
[4] Müller V, Boer RJ de, Bonhoeffer S, Szathmáry E (2018) Biol Rev 93:505-528. https://doi.org/10.1111/brv.12355
PubMed Commons Comment on "Post-translational peptide splicing and T cell responses. Mishto M, Liepe J. (2017) Trends Immunol 38:904-915 [3 December 2017]
**REDESIGNATING SELF AS NOT-SELF MARKERS**
A cell's altruistic service to the population of cells that comprise its host organism may be compromised by a foreign pathogen or by a mutated driver cancer gene (both deemed "non-self"). Such _intracellular_ compromising agents can be first be addressed by _internal_ sensing and auto-destructive mechanisms. Should one of these fail, then _external_ sensing and destructive mechanisms, involving reactions with specific predatory T cells, may come into play. A compromised cell has the option of displaying peptides as pMHC complexes to see if they are recognized by members of T cell populations that, following thymic surveillance and deletion of nascent strongly self-reacting T cells, are programed to eliminate cells displaying non-self markers.
While such markers may arise from foreign proteins or mutated self proteins, Mishto and Liepe note that the scope of markers ("the antigenic landscape") can be greatly increased by redesignating potential self markers (unspliced peptides in pMHC complexes) as non-self (1). This creation of foreign from self is achieved by splicing and trimming non-contiguous peptides to create novel peptides that would not have passed thymic filters and so would be seen as non-self. Two corollaries of this are that such peptide splicing must _not occur in the thymus_ and that, to militate against autoimmunity, extra-thymic specific splicing of separate protein segments would _not occur randomly_ in uncompromised cells.
Thus, some elements of an _internal_ sensing mechanism within a compromised cell would be needed to foster the extension of the antigenic landscape. The growing evidence for such a mechanism in the antigen presentation pathway (intracellular self/non-self discrimination) is presented elsewhere (2). I agree that "the unexpectedly large frequency and amount of … spliced peptides may … have profound implications for the concept of self/nonself peptide presentation" (3).
1.Mishto M, Liepe J. (2017) Post-translational peptide splicing and T cell responses. _Trends in Immunology_ 38:904-915 < PMID:28830734>
2.Forsdyke DR (2015) Lymphocyte repertoire selection and intracellular self/not-self discrimination: historical overview. _Immunology and Cell Biology_ 93:297-304. <PMID:25385066>
3.Liepe J et al. (2016) A large fraction of HLA class I ligands are proteasome-generated spliced peptides. _Science_ 354:354-358.< PMID:27846572>
PubMed Commons: Transcribed Junk Remains Junk If It Does Not Acquire A Selected Function in Evolution. Sverdlov E. Bioessays. [30 Nov 2017].
CRISPR SPACERS PROVIDE "JUNK" VLA RNAs
A "peculiarity of human thinking" invokes sad head-shaking in some quarters. It is argued, not only that "the vast majority of low abundant transcripts are simply junk," but also that such junk is "simple" (1). Those led to think that junk DNA serves the organism (i.e. can under some conditions be functional and hence selectively advantageous) are labelled "determinists." They can scarcely be distinguished from "ID believers"! There is no mention of the two-decade-old view that very low abundance transcripts (VLA RNAs) represent an intracellular antibody-like repertoire, for which much evidence has since accumulated (2-4).
For microorganisms, the CRISPR system provided a clear example of the functionality of the transcription of their spacer "junk DNA." Ledford notes that the system "adapts to, and remembers, specific genetic invaders in a similar way to how human antibodies provide long-term immunity after an infection" (5). Just as we have germline cascades of V genes that confer immunological specificity on B and T lymphocytes, so microorganisms have their germline spacers that confer a similar specificity on their RNA populations. However, the functionality of an individual spacer "sense" transcript is only tested when a virus with a specific "antisense" sequence enters the cell. Transcription is conditional. The selective advantage can only emerge when the corresponding pathogen attacks.
Thus, the analytical problem is not so "simple" as showing by experimental DNA deletion that the transcript of a specific eukaryotic gene is functional, or as postulating a requirement for "unacceptably high birth rates." Deletion of a single human V-region gene could show no selective effect if no corresponding pathogens invaded the body. Even if there were such an invasion, other V-regions would likely be able to compensate for the deletion. Similarly, deleting a segment of "junk" DNA is unlikely to impact survival if some of the wide spectrum of alternative "junk" transcripts can compensate for this defect in the RNA antibody-like repertoire.
1. Sverdlov E (2017) Transcribed junk remains junk if it does not acquire a selected function in evolution. BioEssays doi: 10.1002/bies.201700164. <PMID:29071727>
2. Cristillo AD, Mortimer JR, Barrette IH, Lillicrap TP, Forsdyke DR (2001) Double-stranded RNA as a not-self alarm signal: to evade, most viruses purine-load their RNAs, but some (HTLV-1, Epstein-Barr) pyrimidine-load. J Theor Biol 208:475-491. < PMID:11222051>
3. Forsdyke DR, Madill CA, Smith SD (2002) Immunity as a function of the unicellular state: implications of emerging genomic data. Trends Immunol 23:575-579. <PMID:12464568>
4. Forsdyke DR (2016) Evolutionary Bioinformatics. 3rd edition. Springer, New York, pp. 279-303.
5. Ledford H (2017) Five big mysteries about CRISPR's origins. Nature 541:280-282.< PMID:28102279>
Viral taxonomy: the effect of metagenomics on understanding the diversity and evolution of viruses
(2017) EMBO Reports 18:1693-1696 Philip Hunter (Posted to PubMed Commons Oct 2 2017)
VIRAL REPRODUCTIVE ISOLATION WITHIN A COMMON HOST CELL
This otherwise admirable article <PMID:28877930> begins with the curious assertion that, "since they depend on their host for replication," then viruses cannot "be categorized as species on the basis of reproductive isolation." The latter prevents recombination between organisms and so forms the most generally accepted definition of species. Viruses species whose members share a common host cell, and depend on that cell for their replication, are still able to retain their species individuality. Their members do not mutually destroy each other by recombinational blending of their genomes. They are reproductively isolated from each other.
When we compare two viral species that have a common host cell, with two viral species that, even within a common host, do not share a common cell, we would expect to observe a fundamental difference related to their reproductive isolation mechanism. If that fundamental difference is found to apply to other viral pairs that occupy a common host cell, then a fundamental isolation mechanism has been identified.
Such a difference was first related to the base compositions of insect viruses (1), a then to the base composition of herpes viruses (2). A more extreme example arose from studies of retroviruses that share a T lymphocyte host. The AIDS virus (HIV1) and human T cell leukaemia virus (HTLV1), can be assumed to have evolved from a common ancestor. Differentiation of members of that ancestral species within a common host cell into two independent populations would have required some mechanism to prevent their blending. Thus, we see today a wide divergence in base compositions. HIV1 is one of the highest AT-rich species know. HTLV1 is one of the highest GC-rich species known (3). There is high differentiation of chromosomal nucleic acids.
In these viruses there has been no opportunity for other reproductive isolation mechanisms to supersede chromosomal mechanisms. Diffusible cytoplasmic products make the subsequent evolution of genic incompatibilities less likely, and being in a common host cell there is no equivalent of prezygotic isolation as conventionally understood (4).
1. Wyatt GR (1952) The nucleic acids of some insect viruses. J Gen Physiol 36:201-205. <PMID:13011277>
2. Schachtel GA et al. (1991) Evidence for selective evolution of codon usage in conserved amino acid segments of human alphaherpesvirus proteins. J Mol Evol 33:483-494. <PMID:1663999>
3. Bronson EC, Anderson JN (1994) Nucleotide composition as a driving force in the evolution of retroviruses. J Mol Evol 38:506-532. <PMID:8028030>
4. Forsdyke DR (1996) Different biological species "broadcast" their DNAs at different (G+C)% "wavelengths". J Theoret Biol 178:405-417. <PMID:8733478>
PubMed Commons Commentary on "Effects of thymic selection on T cell recognition of
foreign and tumor antigenic peptides" by George, Kessler and Levine
PNAS 114: E7875–E7881 [27 Sept 2017]
"CLOSE TO SELF" AND "NEAR SELF"
A major conclusion of this elegant modeling study is that "TCR selection against self-peptides has a minimal influence on the recognition of peptides which are 'close' to self." Thus, "TCR negative selection by host peptides has only a weak suppressive effect on detecting peptides which closely resemble self." This agrees with a somewhat less elegant modeling study which invoked lymphocyte clones selected for anti-"near-self" immune reactivity. These would normally have escaped negative selection (i.e. would have been positively selected; 1). The "near-self" viewpoint contrasted with the then prevailing "altered self" viewpoint (2). However, whereas George et al. (2017) regard their study as "empirical," the earlier study (1) arose from consideration of alloreactive phenomena and recognized implications for cancer immunotherapy in keeping with an "overall objective of optimizing CRL therapy" (3, 4). Full historical reviews are available (5, 6).
1. Forsdyke DR (1975) Further implications of a theory of immunity. J Theor Biol 52: l87-l98.<PMID:50501>
2. Forsdyke DR (2005) "Altered-self" or "near-self" in the positive selection of lymphocyte repertoires? Immunol Lett 100: 103-106.<PMID:15894383>
3. Forsdyke (1977) Grant application: http://www.queensu.ca/academia/forsdyke/NCIgrant01.htm
4. Forsdyke DR (1999) Heat shock proteins as mediators of aggregation-induced "danger" signals: implications of the slow evolutionary fine-tuning of sequences for the antigenicity of cancer cel1s. Cell Stress Chaperone 4: 205-210.<PMID:10590834>
5. Forsdyke DR (2012) Immunology (1955-1975): The natural selection theory, the two signal hypothesis and positive repertoire selection. J Hist Biol 45: 139-161.< PMID:21336661>
6. Forsdyke DR (2015) Lymphocyte repertoire selection and intracellular self/not-self discrimination: historical overview. Immun Cell Biol 93: 297-304.<PMID:25385066>
THEORETICAL BIOLOGY [13 Sept 2017]
MISLEADING BRAIN FIGURE (as detected in Neurosceptic blog) [7 Sept 2017]
PubMed Commons Comment on Yaseem et al. (2017) FASEBJ 31, 2210–2219 "Lectin pathway effector enzyme mannan-binding lectin-associated serine protease-2 can activate native complement C3 in absence of C4 and/or C2" <PMID:28188176> [25 July 2017]
LECTIN PATHWAY STUDIES WITH PLANT MANNOSE-BINDING LECTINS
Papers on the lectin pathway (LP) of complement activation in animal sera generally refer to animal mannose-binding lectins (MBLs), with little reference to work with plant MBLs. For example, citing May and Frank (1973), this fine paper states: "Reports of unconventional complement activation in the absence of C4 and/or C2 predate the discovery of LP." Actually, a case can be made that the discovery of the LP predates May-Frank.
The MASP-binding motif on animal MBL, which is necessary for complement activation, includes the amino acid sequence GKXG (at positions 54-57), where X is often valine. The plant lectin concanavalin-A (Con-A) has this motif at approximately the same position in its sequence (the 237 amino acid subunit of Con-A had the sequence GKVG at positions 45-48). The probability of this being a chance event is very low. Indeed, prior to the discovery of MASP involvement, Milthorp & Forsdyke (1970) reported the dosage-dependent activation of complement by Con-A.
As far as I am aware, it has not been formally shown that MASP is involved in the activation of the complement pathway by this plant MBL. Our studies in the 1970s demonstrated that Con-A activates complement through a cluster-based mechanism, which is consistent with molecular studies of animal MBL showing "juxtaposition- and concentration dependent activation" (Degn et al. 2014). References to our several papers on the topic may be found in a review of innate immunity (Forsdyke 2016).
Degn SE et al. (2014) Complement activation by ligand-driven juxtaposition of discrete pattern recognition complexes. Proc Natl Acad Sci USA 111:13445-13450. <PMID:25197071>
Forsdyke DR (2016) Almroth Wright, opsonins, innate immunity and the lectin pathway of complement activation: a historical perspective. Microb Infect 18: 450-459. <PMID:27109231>
May JE, Frank MM (1973) Hemolysis of sheep erythrocytes in guinea pig serum deficient in the fourth component of complement. I. antibody and serum requirements. J Immunol 111: 1671-1677. <PMID:4750864>
Milthorp PM, Forsdyke DR (1970) Inhibition of lymphocyte activation at high ratios of concanavalin A to serum depends on complement. Nature 227:1351-1352 <PMID:5455141>
Yaseem et al. (2017) Lectin pathway effector enzyme mannan-binding lectin-associated serine protease-2 can activate native complement C3 in absence of C4 and/or C2. FASEBJ 31: 2210-2219 <PMID:28188176>
PubMed Commons Comment on "Nucleolin directly mediates Epstein-Barr virus immune evasion through binding to G-quadruplexes of EBNA mRNA" Lista et al. (2017) Nature Commun [17 July 2017]
IF G-QUADRUPLEXES, WHY SO MANY ADENINES?
It is good to see the problem of EBV immune evasion focused, not on the translation product of EBNA1 mRNA (1), but on the mRNA itself (2). However, it is puzzling that the sequence encoding the glycine-alanine repeats is enriched not only in guanines (Gs), but also in adenines (As). In such a GC-rich genome (60% GC), there is a scarcity of As, yet they are concentrated in the glycine-alanine repeat-encoding region. In other words, codons have been selected for their general purine-richness, not just for their G-richness (3). While it is conceivable that the As somehow assist the formation of G-quadruplexes by consecutive Gs, consideration might have been given to the hypothesis that the G-quadruplexes may be a helpful by-product of the fundamental need to purine-load the mRNA.
EBV is not alone in this respect. EBV and HTLV-1 share common characters. Both are deeply latent, GC-rich viruses. They persist in their human hosts for long periods often with no obvious detrimental effects. Most of their proteins are encoded by pyrimidine-rich mRNAs. The HTLV-1 provirus encodes its pyrimidine-rich mRNAs in its "top" sense strand. But there is a "bottom" strand transcript. This is heavily R-loaded and is translated into a basic zipper protein (HBZ) which is poorly immunogenic and is increasingly seen, like EBNA-1, as playing a major role in immune evasion (4-6).
1. Levitskaya, J. et al. (1995) Inhibition of antigen processing by the internal repeat region of the Epstein-Barr virus nuclear antigen-1. Nature 375:685–688. <PMID:7540727>
2. Lista MJ et al. (2017) Nucleolin directly mediates Epstein-Barr virus immune evasion through binding to G-quadruplexes of EBNA-1 mRNA. Nature Commun 8:16043. <PMID:28685753>
3. Cristillo AD et al. (2001) Double-stranded RNA as a not-self alarm signal: to evade, most viruses purine-load their RNAs, but some (HTLV-1, Epstein-Barr) pyrimidine-load. J Theor Biol 208:475–491.< PMID:11222051>
4. Cook LB et al. (2013) HTLV-1: Persistence and pathogenesis. Virology 435:131–140. <PMID:23217623>
5. Shiohama et al. (2016) Absolute quantification of HTLV-1 basic leucine zipper factor (HBZ) protein and its plasma antibody in HTLV-1 infected individuals with different clinical status. Retrovirology 13:29 <PMID:27117327>
6. Forsdyke DR <a href="http://www.queensu.ca/academia/forsdyke/EBV.htm"> EBV Webpage </a>.
PubMed Commons Comment on: "The CRISPR spacer space is dominated by sequences from the species-specific mobilome," by Shmakov et al. [19 May 2017] BioRxiv referred to in PubMed comment on the Esposito paper.
THE VIRUS-VIRUS ARMS RACE
The authors mention the virus-host arms race, but not the virus-virus (in common host) arms race (1). Thus, they seek to "improve our understanding of the evolution of the CRISPR spacer space and the virus-host arms race." There was a similar omission in a study of phage-host relationships in mycobacteria (2), upon which I have commented (3).
Apart from this, the slopes of regression plots of phage GC% against host GC% (Figs. 3, 4) indicate relative AT-enrichment in phage. The authors acknowledge our study (4), where we note differences in the pressures on individual codon positions between phage and bacteria. However, it is deemed that "GC-content … of microbial genomes, … and the cognate viral genomes show a nearly perfect correlation and are almost identical" (1).
This would not be expected from previous arguments (3) and is supported by the observations that "in most cases, there was indeed considerable AT-bias in phages," relative to hosts, although there are cases where "phage genomes had the same composition as the host" (1). The predicted high variance between phages that affect a common host (3), may be reflected in the scatter of points for phages in Fig. 3.
1. Shmakov SA, Sitnik V, Makarova KS, Wolf YI, Severinov KV, Koonin EV (2017) The CRISPR spacer space is dominated by sequences from the species-specific mobilome. BioRxiv preprint (doi: http://dx.doi.org/10.1101/1... ).
2. Esposito LA, Gupta S, Streiter F, Prasad A, Dennehy JJ (2016). Evolutionary interpretations of mycobacteriophage biodiversity and host-range through the analysis of codon usage bias. Microbiol Genom 2(10):e000079. <pmid:28348827>
3. Forsdyke DR (2016) Elusive preferred hosts or nucleic acid level selection? arXiv Preprint (https://arxiv.org/abs/1612.... ).
4. Mortimer JR, Forsdyke DR (2003) Comparison of responses by bacteriophage and bacteria to pressures on the base composition of open reading frames. Appl Bioinformatics 2:47-62. <pmid:15130833> (see 2003 paper )
PubMed Commons Comment: "Heroes of the engram". Josselyn, Kohler and Frankland. J of Neuroscience 37, 4647-4657 [5 May 2017]
ORGANIC MEMORY
The view that Richard Semon's work was neglected seems to be based on psychologist Daniel Schacter's 1982 text (1). This was reissued with a new title and a few changes in 2001, without mention of the profound interim account by historian Laura Otis (2). While the authors cite my 2006 text on Samuel Butler and Ewald Hering, later work corroborates and extends Otis's study and casts a somewhat different light on the authors' prime hero (3, 4).
Even if offering a list of heroes that is "entirely personal," a paper that extolls the "benefits of exploring the history of science" and of acknowledging our "debts … to those scientists who have offered key ideas," could have mentioned the doubts cast on Semon by Freud and Hertzog, and Semon's dismissal of Butler's work as "rather a retrogression than an advance."
1. Schacter DL (1982) Stranger behind the Engram: Theories of Memory and the Psychology of Science. Hillsdale, NJ: Erlbaum.
2. Otis L (1994) Organic Memory. History and the Body in the Late Nineteenth and Early Twentieth Centuries. Lincoln: University of Nebraska Press.
3. Forsdyke DR (2009) Samuel Butler and human long term memory: is the cupboard bare? J. Theor Biol 258:156-164.<PMID:19490862>
4. Forsdyke DR (2015) "A vehicle of symbols and nothing more." George Romanes, theory of mind, information, and Samuel Butler. History of Psychiatry 26:270-287. <PMID:26254127>
EPONYMS FOR REPRODUCTIVE INCOMPATIBILITY (FOREJT) [17 Feb with Forejt response 20 Feb]
Splendor and misery of adaptation, or the importance of neutral null for
understanding evolution. E. V. Koonin BMC Biology (2016) 14:114 <PMID:28010725>
[Sent to Sandwalk blog and PubMed Commons 3 Jan 2017]
ASSUME A SPHERICAL COW?
Following a multidisciplinary study of milk production at a dairy farm, a physicist returned to explain the result to the farmer. Drawing a circle she began: "Assume the cow is a sphere … ." (1) This insider math joke may explain Koonin's puzzlement that "most biologists do not pay much attention to population genetic theory" (2). The bold statement that "nothing in evolution makes sense except in the light of population genetics," cannot be accepted by biologists when evolution is portrayed in terms of just two variables, a "core theory" that involves "an interplay of selection and random drift." While mathematical biologists might find it "counterintuitive" that "the last common eukaryotic ancestor had an intron density close to that in extant animals," this is not necessarily so for their less mathematical counterparts, who are not so readily inclined to believe that an intron "is apparently there just because it can be" (3). While expediently adopting "null models" to make the maths easier, population geneticists are not "refuted by a <i> new </i> theoretical development." They have long been refuted by <i> old </i> theoretical developments as illustrated by the early twentieth century clash between the Mendelians and the Biometricians (4). It is true that by fiddling with "selection coefficient values" and accepting that "streamlining is still likely to efficiently purge true functionless sequences," the null models can closer approximate reality, a host of further variables – obvious to many biologists – still await the acknowledgement of our modern Biometricians.
1. Krauss LM (1994) Fear of Physics: A Guide for the Perplexed. Jonathan Cape, London.
2. Koolin EV (2016) Splendor and misery of adaptation, or the importance of neutral null for understanding evolution. BMC Biology 14:114 <PMID:28010725>
3. Forsdyke DR (2013) Introns First. Biological Theory 7, 196-203.
4. Cock AG, Forsdyke DR (2008) "Treasure Your Exceptions." The Science and Life of William Bateson. Springer, New York.
PURINE-LOADING AS THERMAL ADAPTATION [1 Jan 2017]
PubMed Commons Commentary on Klitting R, Gould EA & de Lamballerie X (2016) "G + C content differs in conserved and variable amino acid residues of flaviviruses and other evolutionary groups." Infection, Genetics and Evolution 45: 332-340. <PMID:27663721> [5 Dec 2016]
SELECTIVE PRESSURE TO CONSERVE VIRUS SPECIES IDENTITY
The authors correctly note that "the most obvious parameter associated with G + C content is the strength of molecular hybridization of polynucleotide duplexes" (1). Such hybridization controls recombination, which is favored when there is close sequence resemblance between different co-infecting viruses ("complete alignment conserved"), and is impeded when there is less sequence resemblance ("complete alignment variable"). The latter anti-recombination activity can be considered in relation to speciation mechanisms that initiate and retain taxonomic differentiations. As recently noted by Meyer et al., allied species of "viruses that infect the same [host] species and cell types are thought to have evolved mechanisms to limit recombination." Without such limitations the genomes would blend and co-infectants would lose their independence as distinct viral species. Mechanisms overcoming this selective disadvantage include "divergences in nucleotide composition and RNA structure that are analogous to pre-zygotic barriers in plants and animals" (2).
Thus, a nucleic acid region may be "conserved," not only because it encodes a protein (i.e. there is "protein pressure" on the sequence), but because it has a specific nucleotide composition (e.g. "GC-pressure"). While protein pressure mainly affects the first and second codon positions, GC-pressure can affect all codon positions. Indeed, at first and second codon positions there may be conflict between pressures, especially when protein pressure is high (i.e. in regions where amino acid conservation is high); then GC-pressure is constrained to vary only at the more flexible third codon position. In contrast, when protein pressure is low (i.e. in regions where amino acid conservation is low), then GC-pressure has greater freedom to affect all codon positions.
If, to avoid recombination, there is selective pressure on one branch of a diverging line to decrease its GC%, then it would be predicted that "the GC% of nucleotides encoding conserved amino acid (AA) residues" would be "consistently higher than that of nucleotides encoding variable AAs," where the pressure to decrease GC% has fuller rein to encompass all three codon positions (1). Conversely, it would be predicted that when there is pressure on a diverging line to increase GC%, then it would be predicted that the GC% corresponding to conserved codons would be consistently lower than that of non-conserved codons (e.g. Ebolavirus).
For flavivirus "the mean G% of the core conserved AA residues is higher (35%) than that of the variable AA residues (28%), but the mean G3% of the core conserved AA residues (28%) is similar to that of the variable AA residues (29%)." While consistent with the above views, there is need for a similar breakdown for C3% and for information on relative frequencies of synonymous codons (e.g. the two cysteine codons correspond either to low or high GC%). More details of selective anti-recombination pressures are presented elsewhere (3, 4). Similar considerations may apply to codon biases and GC% among mycobacteriophages (5).
1.Klitting R, Gould EA & de Lamballerie X (2016) G + C content differs in conserved and variable amino acid residues of flaviviruses and other evolutionary groups. _Infection, Genetics and Evolution_ 45: 332-340.<PMID:27663721>
2.Meyer JR, Dobias DT, Medina SJ, Servilio L, Gupta A, Lenski RE (2016) Ecological speciation of bacteriophage lambda in allopatry and sympatry. _Science_ (in press) doi: 10.1126/science.aai8446 <PMID:27884940>
3.Forsdyke (2014) Implications of HIV RNA structure for recombination, speciation, and the neutralism-selectionism controversy. _Microbes & Infect_16:96-103. <PMID:24211872>
4.Forsdyke DR (2016) _Evolutionary Bioinformatics_, 3rd edition. Springer, New York.
5.Esposito LA, Gupta S, Streiter F, Prasad A, Dennehy JJ (2016). Evolutionary interpretations of mycobacteriophage biodiversity and host-range through the analysis of codon usage bias. _Microbiol Genomics_ 2(10), doi: 10.1099/mgen.0.000079.
Comments for PubMed Commons on "The RNA World at Thirty: A Look Back with its Author" by Neeraja Sankaran (2016) J Mol Evol. DOI 10.1007/s00239-016-9767-3 Posted 21 Nov 2016
THE RNA WORLD AND DARRYL REANNEY
The title of historian Neeraja Sankaran's paper in a "special historical issue" of the Journal of Molecular Evolution implies that the RNA world idea was formulated 30 years ago (i.e. 1986) by a single author, Walter Gilbert (1). Yet the paper traces the story to authors who wrote at earlier times. Missing from the author list is Darryl Reanney who, like Gilbert, documented a "genes in pieces" hypothesis in February 1978 and went on to explore the RNA world idea with the imperative that error-correcting mechanisms must have evolved at a very early stage (2). Much of his work is now supported (3). However, Sankaran cites the video of a US National Library of Medicine meeting organized by historian Nathaniel Comfort on 17th March 2016 (4). Here W. F. Doolittle, who had consistently cited Reanney, discusses the evolutionary speculation triggered by the discovery of introns in 1977, declaring that "several things came together at that time," things that "a guy named Darryl Reanney had been articulating before that." Furthermore, "it occurred to several of us simultaneously and to Darryl Reanney a bit before – before me anyway – that you could just recast the whole theory in terms of the RNA world." Gilbert himself thought that "most molecular biologists did not seriously read the evolution literature; probably still don't." Indeed, contemporary molecular biologists writing on "the origin of the RNA world," do not mention Reanney (5). Thus, we look to historians to put the record straight.
1.Sankaran N (2016) The RNA world at thirty: a look back with its author. J Mol Evol DOI 10.1007/s00239-016-9767-3 < PMID: 27866234>
2. Reanney DC (1987) Genetic error and genome design. Cold Spring Harb Symp Quant Biol 52:751-757
3.Forsdyke DR (2013) Introns first. Biological Theory 7:196-203 <http://www.queensu.ca/academia/forsdyke/introns3.htm>
4.Comfort N (2016) The origins of the RNA world. Library of Congress Webcast. https://www.loc.gov/today/cyberlc/feature_wdesc.php?rec=7353.
5.Robertson MP, Joyce GF (2012) The origins of the RNA world. Cold Spring Harb Perspect Biol 4:a003608. <PMID: 20739415>
MARKETING IN SCIENCE [9 Nov 2016]
PubMed Commons Commentary on Exposito et al (2016) "Evolutionary interpretations of mycobacteriophage biodiversity and host-range through the analysis of codon usage bias". Microbial Genomics (in press) [3 Nov 2016]
ELUSIVE PREFERRED HOSTS OR NUCLEIC ACID LEVEL SELECTION?
While confirming Richard Grantham's view that "viruses do not closely imitate the use of the [host's] … codon catalogue" (1), Esposito et al. nevertheless consider it a "surprising finding" that "despite having the ability to infect the same host, many mycobacteriophages share little or no genetic similarity" (i.e. similarity in their "GC contents and codon utilization patterns"). Arguing correctly that "efficient translation of a phage's proteins within a host is optimized by the phage's ability to match the codon usage patterns of their hosts," the authors conclude that "the preferred host of many mycobacteriophages is not M. smegmatis, despite their having been isolated on M. smegmatis" (2). Thus, a virus and its elusive preferred hosts would have had similar GC% and codon usages, but the same virus could still infect a less-preferred host (M. smegmatis), where the virus-host similarity would be less evident.
All this rests on the incorrect assumption that efficient translation (protein level selection; 3) is evolutionarily decisive and cannot be overruled by nucleic acid level selection. Another interpretation is that, early in the diversification into distinctive mycobacteriophage species, prototypic phage lines acquired GC% differences that permitted coinfection of a common host cell by eliminating the recombination-dependent blending of sequences (4). Coinfectants either blend or speciate. Selection is primarily at the nucleic acid level. Translation efficiency is secondary. So powerful can be the pressure on genomes to avoid recombination that, in extremis, a virus that needs to translate more rapidly is forced to encode its own tRNAs tailored for this special need (2).
Grantham himself had noted that alpha and beta globin mRNAs are translated within the same cell yet have different GC% values and codon usage patterns (1). A simple evolutionary interpretation is that divergence from a prototypic globin gene had been assisted by early-developing GC% differences. These had impeded the recombinational blending between the emerging alpha and beta genes that would have reversed the divergence process (4). Likewise, Wyatt (5) had found that viruses that could co-infect a common host cell diverged widely in genome GC% (and hence in codon usage pattern), whereas viruses with different hosts differed much less in GC% (and hence in codon usage pattern). Other virus-pair examples include the low GC% HIV and the high GC% HTLV1 that are both hosted by CD4 lymphocytes and are likely derived from the same retroviral ancestor (6). The GC% differences may themselves be an expression of more fundamental oligonucleotide differences that bar recombination (7). Esposito et al. (2) cite work conceding the possibility of nucleic acid level selection (3), but here the emphasis is on selection on RNA secondary structure rather than at the genome-level (i.e. on M. smegmatis DNA).
1. Grantham R, Perrin P, Mouchiroud D (1986) Patterns in codon usage of different kinds of species. Oxford Surveys of Evolutionary Biology 3: 48-81.
2. Esposito LA, Gupta S, Streiter F, Prasad A, Dennehy JJ (2016) Evolutionary interpretations of mycobacteriophage biodiversity and host-range through the analysis of codon usage bias. Microbial Genomics 2(10). doi: 10.1099/mgen.0.000079.
3. Ran W, Kristensen DM, Koonin EV (2014) Coupling between protein level selection and codon usage optimization in the evolution of bacteria and archaea. Mbio 5(2):e00956-14 <PMID: 24667707>
4. Forsdyke DR (1996) Different biological species "broadcast" their DNAs at different (G+C)% "wavelengths". Journal of Theoretical Biology 178:405-417. <PMID: 8733478>
5. Wyatt GR (1952) The nucleic acids of some insect viruses. Journal of General Physiology 36:201-205.
6. Forsdyke DR (2014) Implications of HIV RNA structure for recombination, speciation, and the neutralism-selectionism controversy. Microbes & Infection 16:96-103. <PMID: 24211872>
7. Brbic M, Warnecke T, Krisko A, Supek F (2015) Global shifts in genome and proteome composition are very tightly coupled. Genome Biology & Evolution 7:1519-1532. < PMID: 25971281>
Pubmed comment on "Evolutionary switches between two serine codon sets are driven by selection." By Rogozin et al. (2016) Reviewed by KH Wolfe (Dublin) and J Zhang (UMich)
CONSIDERATION OF NUCLEIC ACID LEVEL SELECTION? [3 Nov 2016]
The authors set out "to investigate the evolutionary factors that affect serine codon set switches" (i.e. between TCN and AGY). Their "findings imply unexpectedly high levels of selection" (1). Indeed, the data strongly support the conclusion that codon mutations "are driven by selection." It is conjectured that the codon mutation "switch would involve as an intermediate either threonine ACN or cysteine TGY, amino acid residues with properties substantially different from those of serine, so that such changes are unlikely to be tolerated at critical functional or structural sites of a protein."
However, it does not follow that the unsuitability of the interim amino acids drove the rapid tandem substitutions. Choice of "coincident codons" has long been seen as influenced by pressures acting at the nucleic acid level (2-4). These pressures evolve in parallel with, and sometimes dominate, protein pressures. One example is purine-loading pressure (3). If this cannot be satisfied by changes at third codon positions, then sometimes the organism must accept a less favorable amino acid. With serine codons, a change from TCN to AGY (i.e. first and second codon positions) can increase purine-loading pressure without compromising the amino acid that is encoded (http://www.queensu.ca/academia/forsdyke/bioinfo4.htm).
1. Rogozin IB, Belinky F, Pavlenko V, Shabilina SA, Kristensen DM, Koonin EV (2016) Evolutionary switches between two serine codon sets are driven by selection. Proc Natl Acad Sci USA www.pnas.org/cgi/doi/10.1073/pnas.1615832113<PMID: 27799560>
2. Bains W. (1987) Codon distribution in vertebrate genes may be used to predict gene length. J Mol Biol. 197:379-388.<PMID: 3441003>
3. Mortimer JR, Forsdyke DR (2003) Comparison of responses by bacteriophage and bacteria to pressures on the base composition of open reading frames. Appl Bioinf 2: 47-62.<PMID: 15130833>
4. Forsdyke DR (2016) Evolutionary Bioinformatics, 3rd edition (Springer, New York).
Please follow the Hypothesis or Wayback links for earlier PubMed Commons comments.
Return to: Bioinformatics/Genomics Index (Click Here)
Return to: Evolution Index (Click Here)
Return to: HomePage (Click Here)
This page was established March 2018 and last updated on 12 March 2018 by Donald Forsdyke.


File this under 'things I never knew I wanted until I saw them': a Lego shooter game. Okay, not a real one, but this short from Andrew Films sells the concept pretty hard. Portal, Skyrim, Bioshock and Counter Strike all get a blocky reimagining and it's impressive how much feeling comes across. Counter Strike in particular really nails it considering the lack of spines/knees on the average Lego man.


Most hotels chains reorganize their categories yearly to keep them current with the average rates that they charge. Hyatt hotels have no capacity controls on standard rooms. The good part about that is that if a major event is in town and rates are quadruple what they normally are, you can still use the regular amount of points as long as the hotel is not sold out of standard rooms.
130 hotels are going up in category while 129 hotels are going down in category this year. That's a whole lot more fair than Marriott's ridiculously lopsided 2019 changes. But there are still lots of pain points here.
Book stays before 3/18 at 11:01pm CT (12:01am ET on 3/19) to lock in current rates for future stays at hotels that are going up. You can book stays up to a year in advance. Almost all hotel stays are cancellable for free until a certain amount of time before the stay (read the fine print). If you have a reservation at a hotel for after 3/18 that is going down, you will automatically receive a points refund.
Note that you won't be able to change the dates on a reservation after the price goes up, your only options are to use the stay or cancel it and get your points back.
Hotels going up from category 4 to 5 will no longer be bookable with anniversary nights from the Chase World of Hyatt credit card. You can read more about the new World of Hyatt card here.
The Chase World of Hyatt credit card also offers bonus free nights upon reaching several spending thresholds, those too are limited to category 1-4, which makes hotels climbing from category 4 to 5 particularly painful.
Hyatt's current award chart is below and it now includes SLH hotels, which is why they added a category 8 recently. Luckily none of Hyatt's properties are creeping into category 8 with this change.
Newly eligible hotels for anniversary nights include Hyatt Regency Jersey City, Hyatt Regency Chesapeake Bay Golf Resort Spa and Marina, Hyatt Centric Waikiki Beach, Andaz San Diego, Park Hyatt Istanbul, Park Hyatt Zanzibar, and Hyatt Centric Chicago.
Luxury Andaz hotels in London, NYC, San Diego, drop from a category 6 to 5.
A lot of the most valuable and popular anniversary night hotels are going away. Those include the Hyatt Centric South Beach Miami, Hyatt Regency Coconut Point Resort and Spa, Andaz Costa Rica Resort at Peninsula Papagayo, Hyatt Regency Amsterdam, and Hyatt Regency Hong Kong Tsim Sha Tsui.
Maui gets hit hard, with the Andaz climbing to category 7 and the Hyatt Regency climbing to category 6.
Category 5 luxury bargains like the Park Hyatt Buenos Aires, Park Hyatt Mallorca, Park Hyatt Seoul, Park Hyatt Abu Dhabi, and the Andaz Mayakoba near Cancun all become less of a bargain, going up from category 5 to 6.
Tokyo loses a highly rated bargain as the Andaz joins the Park Hyatt there at category 7.
A true Maldives bargain, the Park Hyatt, will also climb to category 7.
No top-tier category 7 hotels are going down in category.
27 Comments On "Last Chance To Book Awards Before Hyatt 2019 Annual Category Changes, Lock In Lower Rates And Anniversary Nights At Hotels Getting More Expensive Now!"
Definitely some pleasant surprises and disappointments, but all reasonable changes. A far cry from Marriott's massacre of raising nearly 346 properties and lowering 37 (including approx. 80 category 5 to cat 6's (and lowering just 3 of them).
Hyatt Place Cleveland/Lyndhurst/Legacy Village, was 1, now 2.
Will miss redeeming nights at the excellent Andaz Papagayo in Costa Rica and Hyatt Regency Coconut Point.
Brother just moved to Lyndhurst so we stayed at Legacy village for a whole week on points. Unreal that it was only 5k/night.
Yup, amazing deal at category 1. Sad to see it climb.
Any info on Ziva or Zilara.
No changes for the all-inclusives.
Hyatt Regency Coconut Point. Their water parks are amazing. Book three rooms there for the grandkids every spring break using my suite upgrade awards for two of the rooms. My cost would be $800 a night per suite. Total cost $11,200 plus $3200 for the third room so $14,500. Plus no resort fee or parking fee as I am Globalist. Breakfast in the club is awesome as are the snacks for the kids all day. We eat dinner in the club with the grands when we babysit as the appetizers are substantial. Point total is 270,000 as I use three of my free night certificates. Now it will be 420,000 and I won't be able to use the category 1-4 free night certificates. Big difference.
Hyatt place fair lawn is in the eruv and walking distance from 2 shuls. So definitely a cheap point option for anyone who needs to be in the nyc suburbs over shabbos.
are all major hotel chains capacity controlled? like hilton,hyatt marriott. they all have same prices for standard rooms ,only stash rewards is different?
Very excited about Hyatt Regency On The Hudson moving to cat 4. Its stunning hotel! Now can use the anniversary free night.
Cheers for the Hyatt Place Paramus and Hyatt Regency Chesapeake Bay!
At least the confidante Miami Beach was spared!
so sad, our kids have love coconut point. But the good news is that this happened in time for us to recalibrate, we just snagged 3 nights there while kids are off from school in April. SW and jetblue = 11k rt per person. Fll not so close but fewer miles for us coming from Chicago. hmm… 17k miles vs an extra 1.5 hours each way.
Dan, do you know anything about the Hyatt Place Portland- old port. Looking to go in August but will Book now if it's going up a category.
It's going up from category 3 to 4.
If you book a free night stay before 3/18 and want to change the date once it already has moved into a cat 5 will hyatt allow that?
Can anyone advise if it's even possible to become a lifetime globalist? and what's the best way to earn 100,000,000 points with this card? I was spending a lot on this card and barely got 100,000 points.


text:
Strichen railway station was a railway station in Strichen, Aberdeenshire.

History
The station was opened on 24 April 1865 by the Formartine and Buchan Railway. On the northbound platform was the station building, on the north side was the goods yard and at the west end of the westbound platform was the signal box, which opened in 1891. The station closed on 4 October 1965.

References

Disused railway stations in Aberdeenshire
Beeching closures in Scotland
Former Great North of Scotland Railway stations
Railway stations in Great Britain opened in 1865
Railway stations in Great Britain closed in 1965
1865 establishments in Scotland
1965 disestablishments in Scotland

redpajama_set_name: RedPajamaWikipedia


text:
Subject: TV show themes that take you back
Written By: Brimac40 on 01/30/08 at 10:46 am
I noticed that are threads about songs that take you back . But is there a TV show theme song you hear that takes you back . Mine is All In the Family , every time I hear that I have flash backs of being young , setting in the floor in front of the TV set with my Mom telling to back away from the screen so I wont go blind .
Subject: Re: TV show themes that take you back
Written By: Reynolds1863 on 01/30/08 at 10:50 am
Dallas, when I was a kid I was forbidden to watch it. I'd hide around a corner and watch bits and pieces of it.
Welcome Back Kotter, I wanted to go to the projects of NY because of that show.
The Walton's, because it's my Dad's all time favorite show.
Written By: quirky_cat_girl on 01/30/08 at 10:57 am
I would have to say this one too...as, it is one of my parent's favorites also.
Written By: karen on 01/30/08 at 11:26 am
Starsky and Hutch
Written By: whistledog on 01/30/08 at 11:38 am
Benson. More than just the theme, but in the intro when the Doberman's chase Benson into the mansion. When I bought the DVD set of Season 1, that's the one thing I was waiting to see 8)
I forgot all about the Walton's , that one takes me back too .
Written By: Tia on 01/30/08 at 11:42 am
deinifely "land of the lost."
http://youtube.com/watch?v=D6LZzVCpYDY
cool cheesy but sometimes surprisingly smart show. and the song just is good in its own right.
Written By: CatwomanofV on 01/30/08 at 12:48 pm
All of the above. I spent the entire 70s parked in front of the tube. I could sing/hum just about any show's theme song.
But I think the one that really touches me is the theme from Angie (I'm sure many people even have forgotten that show). The theme was called Different Worlds sung by Maureen McGovern (same one who did "Morning After" from the Poseidon Adventure). I even had the 45 of that song-actually, I think I STILL have it. It reminds me of a special someone from my past.
Written By: sonnyvegas on 01/30/08 at 5:51 pm
Mine would have to be M*A*S*H.
I remember when the first strums of the guitar would come on. My mom would put me and my sister to bed and I could hear it on in the living room.
The worst thing about it was sometimes it would still be light outside and I could still hear kids playing outside. To this day I still get butterflies when I hear it.
Weird, huh?
Written By: cinnabon on 01/30/08 at 5:57 pm
Believe it or not some these game show themes take me back to my childhood:
$10k/20k/25k/50k/100k Pyramid (there were 2 different versions of this theme song, one used on ABC in the 70s and the other one on CBS in the 80s)
Written By: snozberries on 01/30/08 at 10:27 pm
Gimme a Break
not theme song but I really love Sunshine Day and Keep On from the Brady Bunch.
The other day I was thinking about the Chips theme song and the theme from The Bob Newhart show...it was a day or two before Suzanne Pleshette died.... Anyway I came up with a mix of the two songs that worked really together... and maybe with little Taxi thrown in.
Shoot now I have to get a TV themes CD with these songs.
Written By: Tia on 01/30/08 at 11:07 pm
ah, classic. i love the whole-tone modulation.
http://youtube.com/watch?v=M82CUd6isyY
you know how you know you're getting old? when you stop checking out valerie bertinelli and mackenzie phillips (who truth be told i always preferred) and start eyeballing bonnie franklin. that's a lotta woman, right there. 8)
that did take me back
Checking Bonnie Franklin....Lol Oh God I hope I don't start eyeing Schneider!
Written By: cinnabon on 01/31/08 at 6:16 am
I always thought Glenn Scarpelli as Alex was hot on that show. :)
Written By: Brimac40 on 01/31/08 at 6:18 am
I only watched "One Day At A Time" was to see valerie bertinelli .
Written By: Tia on 01/31/08 at 6:44 am
mackenzie phillips was hotter. it's just a fact. :P
Written By: Reynolds1863 on 01/31/08 at 7:48 pm
I agree with you on that. Valarie was a bit too ordinary looking.
I've seen Valarie in those Jenny Craig commercials lately and I think she looks amazing for her age (mid to late 40's); to me, she looks almost the same as she did in the 80s. :)
I bet Eddie Van Halen is kicking himself right about now .
Written By: Philip Eno on 02/01/08 at 7:00 am
Banana Splits
H.R.Pufnstuf and Lidsville . I look back on those shows now and wonder how I knew what was going on not being stoned .
Written By: ladybug316 on 02/01/08 at 3:38 pm
I've always loved the themes from:
"Alice"
"Love, American Style"
"Hello, Larry" (which I will now be humming for 3 days!) ;D
Written By: Philip Eno on 02/01/08 at 3:40 pm
The theme tune from The Goodies.
Written By: gumbypiz on 02/01/08 at 5:52 pm
Mackenzie Phillips, hotter than Valarie? ???
Were you taking the same amount of drugs Phillips was at the time you thought that? Um, drugs r bad, nK? :D
The theme from "Medical Center" (bet no one remembers that one) always brings me back, really strange theme if you think about it.
Ditto for "Ironside".
Written By: Snoopygirl on 02/01/08 at 6:05 pm
Barney Miller
plus a ton more....
Chico and the Man sung very beautifully by Jose Feliciano is another great nostalgic theme song - its lyrics seem even more haunting to me now that Freddie Prinze is dead. :\'(
Written By: 66drivein on 02/03/08 at 1:33 am
I have three that transport me back to the 70's.
I loved those shows.
1. Barny Miller
2. Welcome Back Kotter
3. WKRP in Cincinnati
Written By: robby76 on 02/03/08 at 6:20 am
For my ealry childhood, I'd say Diff'rent Strokes stands out the most!
After that it's Three's Company, One Day At A Time, Wait Till Your Father Gets Home etc
Written By: danootaandme on 02/03/08 at 7:57 am
The Avengers - I sooooooo wanted to be Emma Peel
http://calwestray.tripod.com/images/emma_leather.jpg
Written By: KKay on 02/03/08 at 8:38 am
i just came her to post One Day At A Time...
you got it...I knew i could rely on you for quality.
Written By: loki 13 on 02/03/08 at 10:37 am
Written By: KKay on 02/03/08 at 11:34 am
Baretta : keep your eye on the sparrow.
Well, who didn't? :D ;D ;D
The C*H*I*P*S theme song. That was 70's beyond belief. Still like it though.
The Munster's - I used to watch them in the afternoon
Several theme tunes from the sixties always knocks me back.
Written By: gibbo on 02/04/08 at 4:32 pm
Bought the season on DVD with Diana Rigg the other day. Love the theme (and loved Emma Peel) ::)
Written By: snozberries on 02/18/08 at 5:58 pm
;D and THANK YOU!
Written By: Nosebone on 02/20/08 at 9:57 pm
The theme to The 4:30 Movie.
This was a weekday show in the northeast that dominated my 70s childhood.
Even today, I think of that show ( and its theme song), especially on cold, gray winter afternoons.
Here it is : http://www.youtube.com/watch?v=2es-lfRSDOI (sigh)
Written By: robby76 on 02/20/08 at 10:13 pm
To add to my previous list is The Incredible Hulk! Those closing credits sure were a tearjerker. ;D
I loved that music...it was so haunting. Especially after the Mariette Hartley episode...
Written By: Badfinger-fan on 02/21/08 at 12:41 am
The Courtship Of Eddie's Father
Written By: Cherie70 on 02/24/08 at 5:06 pm
Hawaii 5 O
Chico and the Man
The Rockford Files
Quincy Jones MD
Trapper John MD
The song about the Story Box from Magic Garden
Written By: Howard on 12/26/13 at 7:08 am
http://www.youtube.com/watch?v=PFauw9YnkD0
Magic Garden (this ran from 1972-1984, it ran for 12 years.)
There is a possibility that if the Christmas long lost episode did well, it may be brought back to schedule as of 2014.
Written By: warped on 12/26/13 at 3:16 pm
I can think of so many:
Courtship of Eddie's father
Bugs Bunny/Road Runner
Beverly Hillbillies
Love American Style
HR Puff n stuff
and this one http://www.youtube.com/watch?v=q3w7w58CREY
http://www.youtube.com/watch?v=kuuYvQsN-ak
http://www.youtube.com/watch?v=g9NY8R-LmIw
http://www.youtube.com/watch?v=k7FISjhfpmc
http://www.youtube.com/watch?v=85jKDa2zpus
Written By: Howard on 12/28/13 at 3:09 pm
I swear there was a faster version than this one? ???
good old fashioned sitcoms, I miss those days. :)
They could remake Chico And The Man but they would have to find someone who looks like Freddie Prinze.
http://www.youtube.com/watch?v=qRa9uhiAPBs
Baretta

redpajama_set_name: RedPajamaCommonCrawl


The Breton shirt is reinvented by Claudie Pierlot, as shown by the embroidered C patch on the chest. This T-shirt is adorned with cross-stitch style mountain flowers and a navy blue bouclé trim that gives it all its charm. Wear it with cropped jeans and flat shoes for busy days.


1967 The Sydney Smelting Co.Pty.Ltd., moved from Woolwich and A. V. Jennings Aust. Ltd., took a two year option to buy the land. They submitted a development plan to the Hunter's Hill Council.
(a) Council is unanimously and emphatically opposed to any alteration in the zoning of that part of land at Woolwich owned by the Sydney Smelting Co. Pty. Ltd., which has been zoned under the County of Cumberland Planning Scheme as 'open space' since 1951.
(b) Council firmly believes that land zoned as 'open space' under the County of Cumberland Planning Scheme should be acquired and maintained for that purpose.
1969 But following the Hunter's Hill Council elections, the new aldermen in Council, approved Jennings' plan for development of KELLY'S BUSH voting 5 to 4 in favour. Resistance came from the Hunter's Hill Trust, which succeeded in reducing the proposed plans from three tower blocks of home units, to 60-70 town houses, then finally to 25 suburban houses.
Civic Design Society of N.S.W.
Youth Groups and Student Bodies.
Statement by the President, Civic Design Society, University of N.S.W.
"Why fight for KELLY'S BUSH? Firstly – because a strong and vigorous stand has been taken by local people. Secondly– because its location on the harbour foreshores makes this more than a local issue – it affects thousands of people who use the harbour every day. The number of places where there is substantial bush on the harbour is limited, particularly in the western reaches, and should not be reduced. Thirdly – because, as the Battlers have stated, this is a test case. If a successful stand can be made here, then great hope and help is given to other cases elsewhere in the future. This is a skirmish in a greater battle."
Statement by Kylie Tennant "KELLY'S BUSH is a symbol of our lost land. Take away KELLY'S BUSH and you take away one more assurance that in man is left a possibility for the future. The unborn Australian will ask for his birthright and be handed a piece of concrete."
1970 Deputation to the Premier, Sir Robert Askin and in an attempt to prevent the re-zoning of the land, the development of KELLY'S BUSH. Sir Robert Askin indicated support for the "Battlers" petition, BUT on 3rd June 1971, his Minister for Local Government, signed the document re-zoning this 'open space' land, in favour of residential development.
KELLY'S BUSH BECAME A SYMBOL AND A TEST CASE.
Increased support now came from many places. The Trades and Labour Council of N.S.W. spoke out against the alienation of 'open space'. KELLY'S BUSH became the subject of the first green bans and so a temporary stay of proceedings was brought about.
1973 The Hunter's Hill Council applied to the Federal Government Grants Commission for money to buy the whole of KELLY'S BUSH. This was unsuccessful.
1974 Commissioner Dale appointed by the Hunter's Hill Council to hear objections to the proposed Town Plan, recommended that KELLY'S BUSH should be retained as 'open space'. A Consultant Town Planner called in by the Council, examined the case and agreed with Commissioner Dale's findings.
1976 In spite of these expert opinions, the Hunter's Hill Council, by a narrow majority, voted that the zoning of KELLY'S BUSH be residential.
1977 January – Premier of New South Wales, Mr. Wran, stated that the Government would ensure that no development occurred at KELLY'S BUSH; and that if the Council would agree to purchase KELLY'S BUSH for 'open space' recreation, the Government would contribute half the purchase price.
1977 February – The National Trust of Australia (N.S.W.) sponsored the "National Trust– KELLY'S BUSH Appeal".
1977-1978 The Problem of Radio-active waste in Hunter's Hill. The discovery of some radio-active waste material on KELLY'S BUSH has raised doubts about the appropriateness of this land for residential development.
1981 The Town Clerk, Municipality of Hunter's Hill, stated in an open Council Meeting that the matter of the zoning of Kelly's Bush was now in obeyance, pending the release of the Hunter's Hill Town Plan.
Reproduced with permission of the author, Pip Kalajzich.


text:
WHY IS A GAS ANALYSIS SYSTEM NECESSARY?
There are many reasons for using an online gas analysis system:
The process of fermentation can be constantly monitored and overloading can be detected quickly in the gas phase.
In connection with the recording of data gas values can be proof of adhering to the required limits (e.g. hydrogen sulphide within the CHP operation).
The air supply for the microbiological desulphurization can be optimized and it is possible to automate it using a PI controller.
Security relevant concentrations (upper and lower explosion limit) can and must be monitored, predominantly during batch processes such as dry fermentation.
CHP management – biogas can only be fed into the CHP if it has a certain fixed concentration.
Process values can be used for a superior control system and for the detection of overloads (e. g. hydrogen measurement for fuzzy logic control).
WHICH GASES CAN BE DETERMINED IN WHICH AREAS OF MEASUREMENT?
methane (0-100 vol.-%)
carbon dioxide (0-100 vol.-%)
hydrogen sulphide (0 – 10 /30 / 200 / 1500 / 3000 / 5000 ppm)
oxygen (0-25 vol.-%)
hydrogen (0 – 2000 / 5000 / 20000 / 50000 ppm)
other sensors; more measuring ranges available on request
Measuring principles
All gases are measured undiluted, since dilution of gases
represents an additional inaccuracy.
Multi-point calibration for all sensors, compensating for
residual inaccuracies and achieving higher measuring accuracy over
the entire measuring range.
Infrared dual beam temperature and pressure compensated for CH4 and CO2
without cross sensitivity to other gases, no influences by
water vapor, aging etc.
Electrochemical for H2S, H2 and O2 without cross-sensitivity to other
gas constituents/filtering of other constituents.
Optionally, paramagnetic sensors for O2.
Caution with measurement methods such as heat tone and thermal conductivity.
These are not suitable without restriction for
multi-component mixtures due to cross-sensitivity to other gases
(Attention, biogas contains 6 and more gas components with a wide range of physical and chemical properties).
If needed, the devices can be fitted with more redundant sensors with the same or a different measuring range.
WHY AND HOW OFTEN DO THE SENSORS HAVE TO BE CALIBRATED?
Every gas measuring device must be calibrated and maintained. Electrochemical sensors such as hydrogen sulphide, hydrogen and oxygen always show a drift downwards due to the measuring principle (on average about 5 % per year, but up to a maximum of 2 % per month). We recommend a first check after 6 months (you will be informed by us). Depending on the result of this first check, the further intervals are between 9 and 12 months. During these calibrations, the sensors for methane and carbon dioxide are also checked, which only show a low drift (maximum 2 % per year) – although the accuracy requirement for these gases is usually higher.
HOW LONG IS THE LIFE-SPAN OF THE SENSORS?
Methane and carbon dioxide concentrations are measured with infrared sensors (2-beam method). These sensors have a life-span of several years. The life-span is limited predominantly by the life-span of the infrared source of light. The decrease in intensity is compensated to a large extent by means of comparison with the second beam.
Electrochemical sensors (hydrogen sulphide, oxygen, hydrogen) are used up (even without measuring, simply in the air). As we use high-quality sensors, we can guarantee a life-span of 2 years – also with frequent measurements up to more than once an hour.
WHICH KIND OF MAINTENANCE IS NECESSARY AND WHICH COSTS ARISE FROM IT?
Because we are dealing with a measuring device a regular maintenance is essential. The sensors should be calibrated every 6 to 12 months. The calibration, which is carried out by us, currently costs € 75 per sensor. The prices for new electrochemical exchange sensors are between € 200 – € 350. For long-term operation of the systems the yearly maintenance cost (incl. travel costs) can be calculated at 5 – 10 % of the investment.
HOW MUCH DOES A GAS ANALYSIS SYSTEM COST?
As the systems are adapted to the needs of the customers there is no established price. Depending on the equipment prices range between € 4,000 and € 12,000.
WHICH MEASUREMENT INTERVALS ARE NECESSARY AND POSSIBLE?
Every measuring interval of at least 30 minutes is possible. In normal operation mode a measurement every 1 to 2 hours is recommended. If measuring intervals are longer, changes in the biological process may not be recognized in time. A continuous analysis is also possible but the technical equipment would need to be adapted accordingly.
IS IT POSSIBLE TO MEASURE ANYTHING ELSE?
Yes. It is possible to both integrate sensors and to attach external sensors (e. g. fill level, pressure, pH, gas flow, CHP performance).
WHY DO WE USE INDUSTRIAL COMPONENTS IN OUR DEVICES?
Although industrial components are expensive, they are much more robust and available as spare parts over decades. Thereby we achieve a very high availability of the systems.
HOW CAN DATA BE TRANSFERRED FROM THE GAS ANALYSIS SYSTEM TO A COMPUTER OR A CONTROL SYSTEM?
Using our systems data can be transferred optionally by electrical signal (4..20 mA), serial RS232 or RS422/485 interface (ASCII, Profibus, Modbus RTU) and Ethernet (Modbus TCP, Simatic Fetch/Write, TCP socket). More options are available on demand.
WHAT ARE THE ADVANTAGES OF A BUS?
In contrast to the electrical signal a bus can transmit other data, such as the device status, to the control system. Moreover certain functions can be triggered by a control system/computer. The greater the distance and the number of the values to be transferred, the cheaper the solution with the bus compared to the analogue signal, as wiring and the analogue digital changer become redundant.
SECURITY CONCERNING PROTECTION FROM EXPLOSION?
Each analysis system is fitted with a detonation arrestor, which prevents a flashback of flames. The exhaust pipe of the gas measuring device has to be led off or fed back into the main gas pipe in order to prevent the formation of an explosive mixture in the room where the device is installed.
By using a filter ("Fritte") the gas measuring device sucks in the ambient air and feeds the interior with fresh air. In case of possible leaks in the interior the gas would be led off via the exhaust pipe. In addition, most devices (according to the kind of sensor they are fitted with) are checked for the gas composition of the air for flushing or in the interior. Thus, a possible methane atmosphere can be detected in the interior or in the room where the device is installed.
COMPARISON MEASUREMENT WITH OTHER DEVICES AND LAB ANALYSES?
When carrying out comparison measurements please check the specified accuracy values and the calibration status of the devices. Deviations questioned by a user are often within the specified accuracy values. When calculating the total please consider that there is still at least 4 times the amount of oxygen in form of nitrogen available. Using up oxygen can mean the percentage is even higher. It also needs to be taken into account whether the device used for the comparison is fitted with a temperature and pressure compensation. Without this compensation errors in measurement can account for more than 10 %. Moreover it needs to be considered whether the devices measure the gas as is or whether the humidity is removed with a gas cooler.
When comparing values against lab analyses it has to be taken into account that the latter are often normalized to 100 %, i. e. the total is exactly 100 %. If various components are considered, this does not constitute a problem, but otherwise values for the other components may be too high. If working with lab results it should be checked how accurate the analyses are. Based on our experience the accuracy is 1 to 2 %. When taking samples please make sure to use suitable containers or to carry out the analysis quickly in order to avoid falsification of the results due to gas diffusion. Bags out of plastic are often not suitable for all components (diffusion, absorption).
CAN THE EFFICIENCY OF THE CHP BE DETERMINED BY MEANS OF QUALITY AND VOLUMETRIC FLOW MEASUREMENT?
It depends on how accurate the efficiency needs to be determined. For a general assessment it might be enough, but for a more accurate determination appropriate standards have to be applied. For determining the efficiency the methane concentration and the gas volume flow are required. The gas analysis system as well as the volume measurement should be calibrated immediately before and afterwards. We specify an accuracy of 2 % of the final value of the measuring range for the methane concentration. However, even by calibrating the system the maximum accuracy is only between 0.5 and 1 %, because the certified calibration gases already show an inaccuracy of this scale. Calibration gases with a similar concentration to that of biogas should be used as all sensors are (despite compensation) to a certain extend non-linear. When carrying out flow measurements it is important to know for which gas composition or gas density the specified accuracy is applicable. In practice the accuracy of gas flow measurements are rarely better than 5 %. Often the results of the mass flow are converted to the volume by assuming a notional gas composition. Therefore, when confronted with deviating gas compositions many systems calculate the volume inaccurately.
Also make sure that humidity is not calculated twice by mistake.
WHAT IS THE USE OF A CONCENTRATION COMPENSATION AS PART OF THE GAS FLOW MEASUREMENT?
According to the principle of measurement many gas flow measuring devices are dependent on the gas composition when rendering the measured value as a volume or a mass flow. The devices for thermal mass flow measurement are calibrated at 65 5 CH4 and would show an error in measurement of 10 % at a methane concentration of 50 % depending on the flow, just because of the altered gas composition. If these flow sensors are connected to AWITE's process analysis systems, these errors are recalculated and corrected, because the 3-dimensional optional field and the current gas composition are known.
WHY IS THERE A SMALL AMOUNT (PPM) OF HYDROGEN SULPHIDE AT THE AIR MEASURING POINT?
As we do not adjust the zero points of the sensors automatically, the measured value in the air can be a non-zero value. For example, for a measuring range of 5000 ppm it can happen that 20 ppm are shown at the air measuring point. But it always has to be considered that the ambient air might not completely pure. Therefore the zero point of the sensors with a very small measuring range (e. g at 0..10 ppm) is not adjusted with ambient air but with calibration gas.
MY SYSTEM IS OVERLOADED, BUT THE HYDROGEN CONCENTRATION DOES NOT INCREASE. IS THIS POSSIBLE?
Yes, this can happen. Hydrogen is generated mainly during the acidification of fresh substratum. If highly acidic substratum infiltrates into the system, little or no hydrogen is generated as the hydrogen has already been discharged from the system. For example, if the substratum was pure vinegar, no hydrogen would be generated. Therefore biogas plants cannot be operated purely based on the hydrogen concentration. However, a high hydrogen concentration prevents the degradation of propionic acid, butyric acid etc. and therefore should be avoided.
ACCORDING TO MY CHP MANUFACTURER IT SHOULD BE IMPOSSIBLE FOR MY CHP TO RUN WITH SUCH A LOW METHANE CONCENTRATION. IS THE MEASUREMENT WRONG?
The explosion limits of biogas are between 5 and 15 vol.-% for a methane concentration. Thus the gas is diluted in the CHP. For the inflammability it makes a big difference whether a low methane concentration of say 40 % was formed by a bad gas (i. e. residual of carbon dioxide) or by the air supply for the desulphurization process. In the latter case the gas certainly is more inflammable as the gas has only been mixed with air. Remark: The answers presented here refer to the most modern devices. As our devices are constantly being developed, diverting statements concerning older devices and purpose-built systems may apply.
WHY IS THE MEASURED VALUE NOT EXACTLY 20.95 % O2 AT THE INTEGRATED AIR MEASURING POINT?
Though air is measured in regular intervals, we do not adjust the oxygen value automatically to 20.95 % and the other sensors to 0. If we did, the operator would have less control over the drift behaviour of the sensors. Another disadvantage of the automatic adjustment is that leakages or lack of oxygen are not recognized and sensors are adjusted. For example, the oxygen concentration decreases considerably and measurably by 1 % in a room with people during a working day and increases again after working hours. With AWITE devices the operator can use the display to perform an air adjustment for all sensors.
DOWNLOAD FAQS
AWITE Bioenergie FAQs