A critical reassessment of the role of mitochondria in tumorigenesis

Background Mitochondrial DNA (mtDNA) is being analyzed by an increasing number of laboratories in order to investigate its potential role as an active marker of tumorigenesis in various types of cancer. Here we question the conclusions drawn in most of these investigations, especially those published in high-rank cancer research journals, under the evidence that a significant number of these medical mtDNA studies are based on obviously flawed sequencing results. Methods and Findings In our analyses, we take a phylogenetic approach and employ thorough database searches, which together have proven successful for detecting erroneous sequences in the fields of human population genetics and forensics. Apart from conceptual problems concerning the interpretation of mtDNA variation in tumorigenesis, in most cases, blocks of seemingly somatic mutations clearly point to contamination or sample mix-up and, therefore, have nothing to do with tumorigenesis. Conclusion The role of mitochondria in tumorigenesis remains unclarified. Our findings of laboratory errors in many contributions would represent only the tip of the iceberg since most published studies do not provide the raw sequence data for inspection, thus hindering a posteriori evaluation of the results. There is no precedent for such a concatenation of errors and misconceptions affecting a whole subfield of medical research.

Probing the location of displayed cytochrome b562 on amyloid by scanning tunnelling microscopy.

Amyloid fibres displaying cytochrome b562 were probed using scanning tunnelling microscopy (STM) in vacuo. The cytochromes are electron transfer proteins containing a haem cofactor and could, in principle, mediate electron transfer between the tip and the gold substrate. If the core fibres were insulating and electron transfer within the 3D haem network was detected, then the electron transport properties of the fibre could be controlled by genetic engineering. Three kinds of STM images were obtained. At a low bias (<1.5 V) the fibres appeared as regions of low conductivity with no evidence of cytochrome mediated electron transfer. At a high bias, stable peaks in tunnelling current were observed for all three fibre species containing haem and one species of fibre that did not contain haem. In images of this kind, some of the current peaks were collinear and spaced around 10 nm apart over ranges longer than 100 nm, but background monomers complicate interpretation. Images of the third kind were rare (1 in 150 fibres); in these, fully conducting structures with the approximate dimensions of fibres were observed, suggesting the possibility of an intermittent conduction mechanism, for which a precedent exists in DNA. To test the conductivity, some fibres were immobilized with sputtered gold, and no evidence of conduction between the grains of gold was seen. In control experiments, a variation of monomeric cytochrome b562 was not detected by STM, which was attributed to low adhesion, whereas a monomeric multi-haem protein, GSU1996, was readily imaged. We conclude that the fibre superstructure may be intermittently conducting, that the cytochromes have been seen within the fibres and that they are too far apart for detectable current flow between sites to occur. We predict that GSU1996, being 10 nm long, is more likely to mediate successful electron transfer along the fibre as well as being more readily detectable when displayed from amyloid.

二维流形三角网格模型顶点法矢量估计

提出一种以顶点的一邻域中三角形在该顶点处的顶角与对应三角形的面积比值加权三角面法矢量估计二维流形三角网格模型顶点法矢量的方法.回顾了现有的五种顶点法矢量估计方法,然后给出了新的方法.设计了利用理论法矢量与估计法矢量的夹角作为误差评价标准的实验,应用球体和椭球体模型分析了所涉及的6种估计方法的性能。

Learning by Failing to Explain

Explanation-based Generalization requires that the learner obtain an explanation of why a precedent exemplifies a concept. It is, therefore, useless if the system fails to find this explanation. However, it is not necessary to give up and resort to purely empirical generalization methods. In fact, the system may already know almost everything it needs to explain the precedent. Learning by Failing to Explain is a method which is able to exploit current knowledge to prune complex precedents, isolating the mysterious parts of the precedent. The idea has two parts: the notion of partially analyzing a precedent to get rid of the parts which are already explainable, and the notion of re-analyzing old rules in terms of new ones, so that more general rules are obtained.

Innovation and hybrid genres: disturbing social rhythm in legal practice.

This paper explores the non-adoption of an innovation via the concept of hybrid genres, that is digital genres that emerge from a non-digital material precedent. As instances of innovation these are often resisted because they disturb the order of activity and balance of power relations in a given situation, or require users to make conceptual and physical adaptation efforts that they consider too costly. The authors investigate such issues with a case study of the introduction of a hybrid digital genre, ODR or online dispute resolution, in legal practice

Zazen, philosophy of mind, and the practicality of realising impermanence

This dissertation involves a general overview of the meditative practice of zazen and analytic philosophy of mind while suggesting a potential bridge between them in the form of an analysis of the practicality of realising impermanence. By the end of my argument I hope to have offered up some compelling evidence in favour of the idea that analytic philosophy would benefit greatly from adopting principles which are best learned and expressed through the practice of, and scholarship around, Zen Buddhism and in particular the treatment of the concept of impermanence. I demonstrate the Western philosophical tendency to make dichotomous assumptions about the nature of mind, even when explicitly denying a dualist framework. I do so by examining the historical and philosophical precedent for dualistic thinking in the work of figures such as Plato and Descartes. I expand on this idea by examining the psychology of categorisation - i.e. creating mental categories and boundaries - and demonstrating how such categorisations feeds back into behaviour in practical ways, both positive and negative. The Zen Buddhist principle of impermanence states that all phenomena are impermanent and therefore lack essential nature; this includes intellectual concepts such as the metaphysical framework of the analytic approach to mind. Impermanence is a principle which is realised through the embodied practice of zazen. By demonstrating its application to analytic philosophy of mind I show that zazen (and mindfulness practice in general) provides an ongoing opportunity for clearing up entrenched world views, metaphysical assumptions and dogmatic thinking. This in turn may promote a more holistic and ultimately more rewarding comprehension of the role of first-person experience in understanding the world. My argument is not limited to analytic philosophy of mind but reflects broad aspects of thinking in general, and I explain its application to issues of social importance, in particular education systems.

Excitation of highly conjugated (porphinato)palladium(II) and (porphinato)platinum(II) oligomers produces long-lived, triplet states at unit quantum yield that absorb strongly over broad spectral domains of the NIR.

Transient dynamical studies of bis[(5,5'-10,20-bis(2,6-bis(3,3-dimethylbutoxy)phenyl)porphinato)palladium(II)]ethyne (PPd(2)), 5,15-bis{[(5'-10,20-bis(2,6-bis(3,3-dimethylbutoxy)phenyl)porphinato)palladium(II)]ethynyl}(10,20-bis(2,6-bis(3,3-dimethylbutoxy)phenyl)porphinato)palladium(II) (PPd(3)), bis[(5,5'-10,20-bis(2,6-bis(3,3-dimethylbutoxy)phenyl)porphinato)platinum(II)]ethyne (PPt(2)), and 5,15-bis{[(5'-10,20-bis(2,6-bis(3,3-dimethylbutoxy)phenyl)porphinato)platinum(II)]ethynyl}(10,20-bis(2,6-bis(3,3-dimethylbutoxy)phenyl)porphinato)platinum(II) (PPt(3)) show that the electronically excited triplet states of these highly conjugated supermolecular chromophores can be produced at unit quantum yield via fast S(1) → T(1) intersystem crossing dynamics (τ(isc): 5.2-49.4 ps). These species manifest high oscillator strength T(1) → T(n) transitions over broad NIR spectral windows. The facts that (i) the electronically excited triplet lifetimes of these PPd(n) and PPt(n) chromophores are long, ranging from 5 to 50 μs, and (ii) the ground and electronically excited absorptive manifolds of these multipigment ensembles can be extensively modulated over broad spectral domains indicate that these structures define a new precedent for conjugated materials featuring low-lying π-π* electronically excited states for NIR optical limiting and related long-wavelength nonlinear optical (NLO) applications.

Ovariole number - a predictor of differential reproductive success among worker subfamilies in queenless honeybee (Apis mellifera L.) colonies

A honeybee queen normally mates with 10-20 drones, and reproductive conflicts may arise among a colony's different worker patrilines, especially after a colony has lost its single queen and the workers commence egg laying. In this study, we employed microsatellite markers to study aspects of worker reproductive competition in two queenless Africanized honeybee colonies. First, we determined whether there was a bias among worker patrilines in their maternity of drones and, second, we asked whether this bias could be attributed to differences in the degree of ovary activation of workers. Third, we relate these behavioral and physiological factors to ontogenetic differences between workers with respect to ovariole number. Workers from each of three (colony A) and one (colony B) patrilineal genotypes represented less than 6% of the worker population, yet each produced at least 13% of the drones in a colony, and collectively they produced 73% of the drones. Workers representing these genotypes also had more developed follicles and a greater number of ovarioles per ovary. Across all workers, ovariole development and number were closely correlated. This suggests a strong effect of worker genotype on the development of the ovary already in the postembryonic stages and sets a precedent to adult fertility, so that

The Creative Life of Law: Improvisation, Between Tradition and Suspicion

Originally applying solely to chefs, waiters, dishwashers and the like, New York City (NYC) regulations governing cabaret employees were altered in 1943 to include musicians and entertainers, who until the late 1960’s would be required to hold a NYC Cabaret Employee’s Identification Card. The introduction of these notorious “police cards” occurred roughly contemporaneously to the emergence in after-hours night clubs in Harlem of a new and supposedly “wild”, improvisatory brand of jazz: bebop. This article adds to the many rather practical theories on why these cards were introduced a more abstract discussion coined in terms of the relationship between suspicion and tradition and focusing on differing essences of law and improvisatory jazz. While law breathes tradition and is suspicious of improvisation and unpredictability, the converse is true of jazz. Allusion to tradition in jazz improvisation is often viewed as a betrayal of its creative and spontaneous nature. And yet it is only through its departure from the stable transmission of past meaning that improvisation gains meaning. Law, in contrast, while appearing to be entirely composed of tradition, to transmit some sort of determinate and fixed meaning, is constantly betraying itself. As no two legal actions can be exactly the same, judges must improvise on tradition and past precedent every time they are asked to decide a case. Law can thus neither dispense with nor be completely determined by tradition. The legal decision instead lies on the border between what it “is” and what it otherwise could be and every judicial act is, in some sense, a species of improvisation. This article uses the cabaret cards to explore this uncertain terrain between law and improvisation, between tradition and suspicion.

Jamming the Law: Improvisational Theatre and the 'Spontaneity' of Judgment

Modern ‘nonscripted’ theatre (NST) clearly owes much to improvisation. Perhaps less obviously, and more surprisingly, so too does modern law. In this article I will contend that, despite all the rules of evidence and procedure, statutes and legal precedents that fundamentally govern the decisions and actions of a judge, it is only through ‘spontaneity’ that judgment can take place. This claim may appear strange to those well-versed in the common law tradition which proceeds on the basis of past legal decisions, or reason where no precedent exists. NST, on the other hand, is assumed to rely heavily on the unprecedented and unreasoned. Therefore, when the public watches a NST production, it places its faith in the belief that what is being observed is entirely new and is being produced ‘on the spur of the moment’.

Putting a Price on Prisoner Release: The History of Bail and the Future of Parole

In this article, we argue that the history of bail foretells the future of parole. Under a plancalled the Conditional Post-Conviction Release Bond Act (recently passed into law inthree states), US prisoners can secure early release only after posting ‘post-convictionbail’. As with pre-trial bail, the fledgling model would require prisoners to pay a percent-age of the bail amount to secure their release under the contractual responsibility of acommercial bail agency. If release conditions are breached, bounty hunters are legallyempowered to seize and return the parolee to prison. Our inquiry outlines the origins of this post-conviction bond plan and the research upon which it is based. Drawing on the‘new penology’ framework, we identify several underlying factors that make for a ripeadvocacy environment and set the stage for widespread state-level adoption of this planin the near future. Post-conviction bail fits squarely within the growing policy trendstoward privatization, managerialism, and actuarial justice. Most importantly, though,advocates have the benefit of precedent on their side, as most US states have longrelied on a system of commercial bail bonding and private bounty hunting to manageconditional pretrial release.

Epistolarum Familiarium Liber Unus in The Complete Works of John Milton: Volume XI (672pp.)

This edition of Milton’s Epistolarum Familiarium Liber Unus and of his Uncollected Letters, will appear as 672 pp. of The Complete Works of John Milton Volume XI, eds. Gordon Campbell and Edward Jones (Oxford University Press, forthcoming 2016). A diplomatic Latin text and a new facing English translation are complemented by a detailed Introduction and commentary that situate Milton’s Latin letters in relation to the classical, pedagogical and essentially humanist contexts at the heart of their composition. Now the art of epistolography advocated and exemplified by Cicero and Quintilian and embraced by Renaissance pedagogical manuals is read through a humanist filter whereby, via the precedent (and very title) of Epistolae Familiares, the Miltonic Liber is shown to engage with a neo-Latin re-invention of the classical epistola that had come to birth in quattrocento Italy in the letters of Petrarch and his contemporaries. At the same time the Epistolae are seen as offering fresh insight into Milton’s views on education, philology, his relations with Italian literati, his blindness, the poetic dimension of his Latin prose, and especially his verbal ingenuity as the ‘words’ of Latin ‘Letters’ become a self-conscious showcasing of etymological punning on the ‘letters’ of Latin ‘words’. The edition also announces several new discoveries, most notably its uncovering and collation of a manuscript of Henry Oldenburg’s transcription (in his Liber Epistolaris held in Royal Society, London) of Milton’s Ep. Fam. 25 (to Richard Jones). Oldenburg’s transcription (from the original sent to his pupil Jones) is an important find, given the loss of all but two of the manuscripts of Milton’s original Latin letters included in the 1674 volume. The edition also presents new evidence in regard to Milton’s relationships with the Italian philologist Benedetto Buonmattei, the Greek humanist Leonard Philaras, the radical pastor Jean Labadie (and the French church of London), and the elusive Peter Heimbach.

Structural and kinetic characterization of the LPS biosynthetic enzyme D-alpha,beta-D-heptose-1,7-bisphosphate phosphatase (GmhB) from Escherichia coli

Lipopolysaccharide is a major component of the outer membrane of gram-negative bacteria and provides a permeability barrier to many commonly used antibiotics. ADP-heptose residues are an integral part of the LPS inner core, and mutants deficient in heptose biosynthesis demonstrate increased membrane permeability. The heptose biosynthesis pathway involves phosphorylation and dephosphorylation steps not found in other pathways for the synthesis of nucleotide sugar precursors. Consequently, the heptose biosynthetic pathway has been marked as a novel target for antibiotic adjuvants, which are compounds that facilitate and potentiate antibiotic activity. D-alpha,beta-D-heptose-1,7-bisphosphate phosphatase (GmhB) catalyzes the third essential step of LPS heptose biosynthesis. This study describes the first crystal structure of GmhB and enzymatic analysis of the protein. Structure-guided mutations followed by steady state kinetic analysis, together with established precedent for HAD phosphatases, suggest that GmhB functions through a phosphoaspartate intermediate. This study provides insight into the structure-function relationship of GmhB, a new target for combatting gram-negative bacterial infection.

Ordering effects and choice set awareness in repeat-response stated preference studies

We present an experiment designed to investigate the presence and nature of ordering effects within repeat-response stated preference (SP) studies. Our experiment takes the form of a large sample, full-factorial, discrete choice SP exercise investigating preferences for tap water quality improvements. Our study simultaneously investigates a variety of different forms of position-dependent and precedent-dependent ordering effect in preferences for attributes and options and in response randomness. We also examine whether advanced disclosure of the choice tasks impacts on the probability of exhibiting ordering effects of those different types. We analyze our data both non-parametrically and parametrically and find robust evidence for ordering effects. We also find that the patterns of order effect in respondents' preferences are significantly changed but not eradicated by the advanced disclosure of choice tasks a finding that offers insights into the choice behaviors underpinning order effects. © 2011 Elsevier Inc.

Exposición Internacional 1910. Buenos Aires.: Didactic leisure and international recognition

International exhibitions were greatly responsible for the modernization of western society. The motive for these events was based on the possibility of enhancing the country’s international status abroad. The genesis of world exhibitions came from the conviction that humanity as a whole would improve the continual flow of new practical applications, the development of modern communication techniques and the social need for a medium that could acquaint the general public with changes in technology, economy and society .
Since the first national industrial exhibitions in Paris during the eighteenth century and especially starting from the first Great Exhibition in London’s Hyde Park in 1851 these international events spread steadily all over Europe and the United States, to reach Latin America in the beginnings of the twentieth century . The work of professionals such as Daniel Burnham, Werner Hegemann and Elbert Peets made the relation between exhibitions and urban transformation a much more connected one, setting a precedent for subsequent exhibitions.
In Buenos Aires, the celebration of the centennial of independence from Spain in 1910 had many meanings and repercussions. A series of factors allowed for a moment of change in the city. Official optimism, economical progress, inequality and social conflict made of this a suitable time for transformation. With the organization of the Exposición Internacional the government had, among others, one specific aim: to achieve a network of visual tools to set the feeling of belonging and provide an identity for the mixture of cultures that populated the city of Buenos Aires at the time. Another important objective of the government was to put Buenos Aires at the level of European cities.
Foreign professionals had a great influence in the conceptual and factual shaping of the exhibition and in the subsequent changes caused in the urban condition. The exhibition had an important role in the ways of thinking the city and in the leisure ideas it introduced. The exhibition, as a didactic tool, worked as a precedent for conceiving leisure spaces in the future. Urban and landscape planners such as Joseph Bouvard and Charles Thays were instrumental in great part of the design of the Exhibition, but it was not only the architects and designers who shaped the identity of the fair. Other visitors such as Jules Huret or Georges Clemenceau were responsible for giving the city an international image it did not previously have.
This paper will explore on the one hand the significance of the exhibition of 1910 for the shaping of the city and its image; and on the other hand, the role of foreign professionals and the reach these influences had.