Standards of evidence and causality in regulatory science: Risk and benefit assessment

In this paper we analyze the Russo-Williamson Thesis (RWT) as a standard of evidence in regulatory science, in risk as well as benefit assessment. In our analysis we take account of the recent controversies that have taken place in regulation with respect to the evidentiary requirements necessary for regulatory decision making. RWT's main point is that not only probabilistic but also mechanistic evidence is necessary for being able to infer the existence of causal links. We ask in which way RWT could have an impact upon current decision making about subjecting to regulation (or, to the contrary, leaving them unregulated) certain chemical substances, food stuffs, health claims, and other typical objects of regulation. We show that the application of RWT resolves some of the problems posed by current standards of evidence. RWT makes it possible to determine with higher accuracy if a particular substance should be subjected to regulation or not, even though under certain circumstances RWT itself may turn into a source of regulatory error. The adequacy of RWT as a standard of evidence depends on the precise manner of its application to regulation (particularly the consideration of mechanistic evidence as a complementary or necessary requirement), as well as the assessment of its non-epistemic consequences.     

A new carnivorous dinosaur from the Late Jurassic Solnhofen archipelago

Small Late Jurassic theropod dinosaurs are rare worldwide. In Europe these carnivorous dinosaurs are represented primarily by only two skeletons of Compsognathus, neither of which is well preserved. Here we describe a small new theropod dinosaur from the Late Jurassic period of Schamhaupten in southern Germany. Being exquisitely preserved and complete from the snout to the distal third of the tail, the new fossil is the best-preserved predatory, non-avian dinosaur in Europe. It possesses a suite of characters that support its identification as a basal coelurosaur. A cladistic analysis indicates that the new taxon is closer to maniraptorans than to tyrannosauroids, grouping it with taxa often considered to be compsognathids. Large portions of integument are preserved along its tail. The absence of feathers or feather-like structures in a fossil phylogenetically nested within feathered theropods indicates that the evolution of these integumentary structures might be more complex than previously thought.     

Transient radio bursts from rotating neutron stars

The radio sky is relatively unexplored for transient signals, although the potential of radio-transient searches is high. This was demonstrated recently by the discovery of a previously unknown type of source, varying on timescales of minutes to hours. Here we report a search for radio sources that vary on much shorter timescales. We found eleven objects characterized by single, dispersed bursts having durations between 2 and 30 ms. The average time intervals between bursts range from 4 min to 3 h with radio emission typically detectable for <1 s per day. From an analysis of the burst arrival times, we have identified periodicities in the range 0.4-7 s for ten of the eleven sources, suggesting origins in rotating neutron stars. Despite the small number of sources detected at present, their ephemeral nature implies a total Galactic population significantly exceeding that of the regularly pulsing radio pulsars. Five of the ten sources have periods >4 s, and the rate of change of the pulse period has been measured for three of them; for one source, we have inferred a high magnetic field strength of 5 x 10(13) G. This suggests that the new population is related to other classes of isolated neutron stars observed at X-ray and gamma-ray wavelengths.     

From in vivo to in silico biology and back

The massive acquisition of data in molecular and cellular biology has led to the renaissance of an old topic: simulations of biological systems. Simulations, increasingly paired with experiments, are being successfully and routinely used by computational biologists to understand and predict the quantitative behaviour of complex systems, and to drive new experiments. Nevertheless, many experimentalists still consider simulations an esoteric discipline only for initiates. Suspicion towards simulations should dissipate as the limitations and advantages of their application are better appreciated, opening the door to their permanent adoption in everyday research.     

High-throughput synthesis and catalytic properties of a molecular sieve with 18- and 10-member rings

Crystalline molecular sieves with large pores and high adsorption capacities have many potential applications. Of these materials, zeolites are of particular interest owing to their stability in a wide range of experimental conditions. An aluminophosphate with very large circular channels(5) containing 18 oxygen atoms (18-ring channels) has been synthesized, but in the search for large-pore zeolites, most of the materials which have been synthesized up to now contain only 14-ring channels; the synthesis of zeolites with larger ring structures has been believed to be hindered by the low Si-O-Si bond angles available. A silicogaloaluminate (ECR-34) with unidirectional 18-ring channels was recently reported, but exhibited low micropore volume, thus rendering the material less attractive for catalytic applications. Here we report the structure and catalytic activity of the silicogermanate zeolite ITQ-33; this material exhibits straight large pore channels with circular openings of 18-rings along the c axis interconnected by a bidirectional system of 10-ring channels, yielding a structure with very large micropore volume. The conditions for synthesis are easily accessible, but are not typical, and were identified using high-throughput techniques.     

DNA damage defines sites of recurrent chromosomal translocations in B lymphocytes

Recurrent chromosomal translocations underlie both haematopoietic and solid tumours. Their origin has been ascribed to selection of random rearrangements, targeted DNA damage, or frequent nuclear interactions between translocation partners; however, the relative contribution of each of these elements has not been measured directly or on a large scale. Here we examine the role of nuclear architecture and frequency of DNA damage in the genesis of chromosomal translocations by measuring these parameters simultaneously in cultured mouse B lymphocytes. In the absence of recurrent DNA damage, translocations between Igh or Myc and all other genes are directly related to their contact frequency. Conversely, translocations associated with recurrent site-directed DNA damage are proportional to the rate of DNA break formation, as measured by replication protein A accumulation at the site of damage. Thus, non-targeted rearrangements reflect nuclear organization whereas DNA break formation governs the location and frequency of recurrent translocations, including those driving B-cell malignancies.     

Organizational Model Design for Small Coffee Farmers in the Municipality of Viotá - Colombia Case Study: Creo en el Agro

Systemic Practice and Action Research - An organizational design proposal is made for Creo en el Agro, an organization made up of small coffee growers who were victims of the armed conflict in the...     

Sintering study of Ti6Al4V powders with different particle sizes and their mechanical properties

Ti6Al4V powders with three different particle size distributions (0-20, 20-45, and 45-75 μm) were used to evaluate the effect of the particle size distribution on the solid-state sintering and their mechanical properties. The sintering kinetics was determined by dilatometry at temperatures from 900 to 1260℃. The mechanical properties of the sintered samples were evaluated by microhardness and compression tests. The sintering kinetics indicated that the predominant mechanism depends on the relative density irrespective of the particle size used. The mechanical properties of the sintered samples are adversely affected by increasing pore volume fraction. The elastic Young's modulus and yield stress follow a power law function of the relative density. The fracture behavior after compression is linked to the neck size developed during sintering, exhibiting two different mechanisms of failure:interparticle neck breaking and intergranular cracking in samples with relative densities below and above of 90%, respectively. The main conclusion is that relative density is responsible for the kinetics, mechanical properties, and failure behavior of Ti6Al4V powders.     

Hidden complexity in the mechanical properties of titin

Individual molecules of the giant protein titin span the A-bands and I-bands that make up striated muscle. The I-band region of titin is responsible for passive elasticity in such muscle, and contains tandem arrays of immunoglobulin domains. One such domain (I27) has been investigated extensively, using dynamic force spectroscopy and simulation. However, the relevance of these studies to the behaviour of the protein under physiological conditions was not established. Force studies reveal a lengthening of I27 without complete unfolding, forming a stable intermediate that has been suggested to be an important component of titin elasticity. To develop a more complete picture of the forced unfolding pathway, we use mutant titins--certain mutations allow the role of the partly unfolded intermediate to be investigated in more depth. Here we show that, under physiological forces, the partly unfolded intermediate does not contribute to mechanical strength. We also propose a unified forced unfolding model of all I27 analogues studied, and conclude that I27 can withstand higher forces in muscle than was predicted previously.     

Clones identification of Sequoia sempervirens (D. Don) Endl. in Chile by using PCR-RAPDs technique

A protocol of polymerase chain reaction-random amplified polymorphic DNAs (PCR-RAPDs) was established to analyse the gene diversity and genotype identification for clones of Sequoia sempervirens (D. Don) Endl. in Chile. Ten (out of 34) clones from introduction trial located in Voipir-Villarrica, Chile, were studied. The PCR-RAPDs technique and a modified hexadecyltrimethylammonium bromide (CTAB) protocol were used for genomic DNA extraction. The PCR tests were carried out employing 10-mer random primers. The amplification products were detected by electrophoresis in agarose gels. Forty nine polymorphic bands were obtained with the selected primers (BG04, BF07, BF12, BF13, and BF14) and were ordered according to their molecular size. The genetic similarity between samples was calculated by the Jaccard index and a dendrogram was constructed using a cluster analysis of unweighted pair group method using arithmetic averages (UPGMA). Of the primers tested, 5 (out of 60) RAPD primers were selected for their reproducibility and high polymorphism. A total of 49 polymorphic RAPD bands were detected out of 252 bands. The genetic similarity analysis demonstrates an extensive genetic variability between the tested clones and the dendrogram depicts the genetic relationships among the clones, suggesting a geographic relationship. The results indicate that the RAPD markers permitted the identification of the assayed clones, although they are derived from the same geographic origin.