Here is a brief summary of allergy research as an index to Schadewaldt
1900 Posselt (1:370; 4:44)
enteritis membranacea used synonymous to asthma
1902 Kratschmer (2:100)
hay fever is triggered by trigeminus reflex Continue reading Allergy research 1900-1933
Sometimes erroneously described as global village phenomenon the notion of a small world goes back to an experiment by Stanley Milgram (who became famous with the “obedience to authority” experiment – I did not know until last weeks that the punishing experiments had been repeated here in Munich where 85 percent of the subjects continued until to the end!).
The small world theory says that everyone in the world can be reached through a short chain of social acquaintances. The concept gave rise to the famous phrase of phrase six degrees of separation – I believe that a scientist may even reach another scientist in 4-5 steps.
My first PubNet example here is to reach F. Sanger by joint co-authors. This doesn’t work – my estimate would be 3 intermediary steps.
My second PubNet example is to reach N. Morton (the foreword of his anniversary book says that a qualification of a genetic epidemiologist can be counted as “Newton”-points – the number of joint publications with Professor Morton).
Arxive.org has the largest study so far: 6,6 steps in 30 billion messenger conversations among 240 million people.
There is no need for another diagnosis here. There is also no need about the impact of the automobile industry – I have published in 1993 the first large epidemiological study about traffic and respiratory health here in Munich.
What could we do? People need to move but need alternatives to public transport or 1000kg cars.
One such alternative is being the Swiss made twike Twike that I could get for a ride – excellent driving experience (quite fast too!) while needing only 0.5 l equivalent per 100 km. Although I am also attracted by recumbents and gyrocopters, this seems to be the best alternative ;-)
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In my experience Google Scholar already shows more counts than ISI Web of Science. A new paper in first monday highlights another search engine that allows even truncation of search terms*: Exalead is a European (Paris) based search engine which does allow truncation and has a nice interface too.
A new series of papers in the BMJ discusses some alarming consequences of “impact” measurements
The impact factor now has a worrying influence not just on publication of papers but on the science behind them too … One consequence has been to make universities prioritise laboratory based life sciences that produce research published in the highest impact factor journals, causing substantial damage to the clinical research base.
that goes beyond the previous view of Seglen.
With a new child, people are always asking if the baby looks like the father or the mother – probably a prehistoric social reflex to confirm that this is your offspring that you are caring about.
Face recognition clearly is a science of its own – a lot of heuristics and Bayesian computing – more at face-rec.org – and even a big business if you think of automatic passport control or age determination for goods that are only allowed for adults.
Face recognition works quite robust as I found in the advanced online demo at betaface.com. A new browser plugin from polar rose will even allows to annotate web pictures – Orwell meets Flickr.
NYT today has an interesting article about freebase (no, nothing about cocaine here) a forthcoming sematic web approach.
On the Web, there are few rules governing how information should be organized. But in the Metaweb database, to be named Freebase, information will be structured to make it possible for software programs to discern relationships and even meaning.
For example, an entry for California’s governor, Arnold Schwarzenegger, would be entered as a topic that would include a variety of attributes or “views†describing him as an actor, athlete and politician — listing them in a highly structured way in the database.
That would make it possible for programmers and Web developers to write programs allowing Internet users to pose queries that might produce a simple, useful answer rather than a long list of documents.
Valleywag – the famous tech gossip – also has something about semantic webs.
Ever since I created a linkage map of the human genome with old-fashinoned crimap, we are talking about “mapping” diseases and genes. GIS mapping also ever increases – see the interesting first monday article Many, many maps: Empowerment and online participatory mapping, that has a lot of details about grassroots initiatives building on Keyhole/Google technology. I learned also about Common Census – looks like grassroot epidemiology.
It is certainly hard to understand how early life events are leading to later disease. Here is an incredible nutrigenomics story done in agouti mice:
We find that the somatic epigenetic state of Avy is affected by in utero methyl donor supplementation only when the allele is paternally contributed. Exposure to methyl donor supplementation during midgestation shifts Avy phenotypes not only in the mice exposed as fetuses, but in their offspring. This finding indicates that methyl donors can change the epigenetic state of the Avy allele in the germ line, and that the altered state is retained through the epigenetic resetting that takes place in gametogenesis and embryogenesis. Thus a mother’s diet may have an enduring influence on succeeding generations.
This is to convince me that the thymic stromal lymphopoietin (TSLP) is a master switch in allergy
Skin-specific overexpression of TSLP resulted in an AD-like phenotype, with the development of eczematous lesions containing inflammatory dermal cellular infiltrates, a dramatic increase in Th2 CD4+ T cells expressing cutaneous homing receptors, and elevated serum levels of IgE.
Topical application of the physiologically active ligand [1{alpha},25-(OH)2D3; calcitriol] of the vitamin D receptor, or of its low-calcemic analog MC903 (calcipotriol; Dovonex), induces TSLP expression in epidermal keratinocytes, which results in an atopic dermatitis-like syndrome.
TSLP, synergistically with interleukin 1 and tumor necrosis factor, stimulates the production of high levels of Th2 cytokines by human mast cells (MCs) … TSLP is released by primary epithelial cells in response to certain microbial products, physical injury, or inflammatory cytokines.
Proinflammatory TNFalpha or IL-1alpha and Th2 (IL-4 or IL-13) cytokines synergized to induce the production of TSLP in human skin explants … Our data provide the first evidence of TSLP induction and subsequent DC activation in human skin.
Mice with an IEC[intestinal epithelial cell]-specific deletion of IKKbeta show a reduced expression of the epithelial-cell-restricted cytokine thymic stromal lymphopoietin in the intestine and, after infection with the gut-dwelling parasite Trichuris, fail to develop a pathogen-specific CD4+ T helper type 2 (TH2) response and are unable to eradicate infection. Further, these animals show exacerbated production of dendritic-cell-derived interleukin-12/23p40.
… (TSLP) and interleukin-7 share a common receptor chain, IL-7Rα … The gene encoding the IL-7Rα chain is polymorphic, and investigation of inhalation allergic patients compared with controls showed significant association with two alleles at position +1237 and +2087.
… TSLP represents a master switch of allergic inflammation at the epithelial cell and dendritic cell interface.
Can you find the problem in the following abstract
…We report a case-control study of 6,106 individuals from the UK, Vietnam and several African countries with invasive pneumococcal disease, bacteremia, malaria and tuberculosis. We genotyped 33 SNPs, including rs8177374, which encodes a leucine substitution at Ser180 of Mal. We found that heterozygous carriage of this variant associated independently with all four infectious diseases in the different study populations. Combining the study groups, we found substantial support for a protective effect of S180L heterozygosity against these infectious diseases (N = 6,106; overall P = 9.6 times 10-8)…
The BMJ explained last year – why p-values (or relative risks alone) do not make so much sense
Unless ratio measures are reported with the underlying absolute risks, readers cannot judge the clinical significance of the effect. Consider the following example. Readers may be told that the relative risk of death with drug A compared with placebo is 0.5; in other words, people who take drug A are half as likely to die as people who take placebo. But without the underlying absolute risks—the chance of death in each group—the information is incomplete.1 A relative risk of 0.5, for example, is compatible with a wide range of changes in the risk of death: from 20% to 10%, from 1% to 0.5%, and from 0.0004% to 0.0002%.
I truly liked the recent Sjoblom study while a new Science letter now raises heavy criticism:
… put into stark reality the challenges facing the Human Cancer Genome Project (HCGP). One wonders about the merits of such high-cost, low-efficiency, and ultimately descriptive-type “brute force” studies. Although previously unknown mutated genes were unearthed, the functional consequences of most of these and their actual role in tumorigenesis are unknown, and even with that knowledge we are a long way from identifying new therapeutic targets.
This seems to be the open wound of modern biology: all these high throughput driven genotyping / expression profiling / metabolome scanning approaches are mainly money & impact & activity driven – parameter or hypothesis-free has become a fashionable buzz phrase while only a few years ago it would have been an affront to every serious researcher.
Funny to see also the new Nature initiative opentextmining.org as nobody wants to read the results of these studies. So at least computers should be able to do that. Fail better…
Similar criticism of the Neanderthal studies but a different argument
However, although such comparisons are of interest, it is not the static genome but rather the dynamic proteome that determines the phenotype of an organism. Salient examples include the caterpillar and the tadpole, which share
genomes with the butterfly and frog, respectively, but which have very different proteomes making them into very different organisms.
Thus, rather than performing untargeted comparisons of sizable genomes, we suggest that it might be more useful to address this question using a standard hypothesis-driven approach.
I have tested several programs for their usefulness of showing Powerpoint slides on the web- some packages create standalone pages only while others have major problems with figures, graphics or transitions (or are quite expensive).
A rather simple method works at least in part – loading a .ppt file in Open Office Impress and exporting it to .swf. The flv player, however, creates a messy display as it doesn’t use the full display area.
Another option is to export all pages as 800×600 .jpg files and mount them in File Show Maker to a standalone flash film – as seen below in a talk that I have given in 2006:
Did you ever came across DANN sequencing or plasmid DANN?
Here is my explanation: Native German MS WORD always corrects DNA to DANN (“then”). So if you don’t check your text, and your editor doesn’t check your text, and your reviewer doesn’t check your text – you will get an immortal entry in PUBMED like the guys below:
You may even earn money with typos …
A nice PNAS paper gives in its supplement 4 the MCM6 and mtDNA 16209 genotypes of some prehistoric bones AND of all authors – excellent! The study itself is also interesting as we learn about the true wild-type allele in early Neolithic Europeans – they could not digest milk.