Unnatural acts: The transition from Natural Principles to Laws of Nature in Early Modern science

This paper's aim is to explain the transition that occurred during the Early Modern period, from Principles of Nature to Laws of Nature. Natural Principles are taken to be innate to substances and arise from their natures, while Laws of Nature are external and imposed from without. The paper takes the view that to explain this transition, one needs to examine the history of philosophical theories of substantial action. It argues that during the late Middle Ages and in the Early Modern era, philosophers began to disentangle substantial actions from the nature of substances. This process of disentangling action eventually led to the concept of Laws of Nature, according to which laws compel a body to act in a certain way even though its nature does not.     

Year-round activity patterns in a hyperdiverse community of rainforest amphibians in Madagascar

Madagascar hosts a high diversity of amphibians estimated at over 500 species, nearly all of them endemic. Surprisingly few data are available on the activity cycles of this fauna, despite its importance for ecological, evolutionary and conservation research. Here we report the results of a year-round survey of amphibians along a transect bordering the Analamazaotra forest near Andasibe in central eastern Madagascar. During 120 transect walks evenly spaced through the year, a total of 2530 individuals of 40 species of anurans was observed. Abundance was higher during the warm/rainy season (December to April) and peaked in February. Of the five climatic predictors measured, only mean temperature and relative humidity showed high importance values, and multi-model averages indicate that these two variables have a strong effect on amphibian abundance along the transect. Species richness showed no evident peak during the study period and was best explained by a model including average temperature and rainfall. Canonical correspondence analysis indicates that Boophis sibilans, B. tephraeomystax, B. boehmei and Plethodontohyla notosticta were more frequently encountered along the transect on cold and humid days while Plethodontohyla mihanika, Gephyromantis boulengeri and Spinomantis aglavei were distinctly more abundant on cold and dry days, and Paradoxophyla palmata on warm and dry days. The results of our study flag a number of species as suitable candidates for future monitoring initiatives and suggest that a simple combination of visual and acoustic surveys can estimate amphibian activity with high sample sizes in Madagascar’s rainforests.     

Transport and Anderson localization in disordered two-dimensional photonic lattices

One of the most interesting phenomena in solid-state physics is Anderson localization, which predicts that an electron may become immobile when placed in a disordered lattice. The origin of localization is interference between multiple scatterings of the electron by random defects in the potential, altering the eigenmodes from being extended (Bloch waves) to exponentially localized. As a result, the material is transformed from a conductor to an insulator. Anderson's work dates back to 1958, yet strong localization has never been observed in atomic crystals, because localization occurs only if the potential (the periodic lattice and the fluctuations superimposed on it) is time-independent. However, in atomic crystals important deviations from the Anderson model always occur, because of thermally excited phonons and electron-electron interactions. Realizing that Anderson localization is a wave phenomenon relying on interference, these concepts were extended to optics. Indeed, both weak and strong localization effects were experimentally demonstrated, traditionally by studying the transmission properties of randomly distributed optical scatterers (typically suspensions or powders of dielectric materials). However, in these studies the potential was fully random, rather than being 'frozen' fluctuations on a periodic potential, as the Anderson model assumes. Here we report the experimental observation of Anderson localization in a perturbed periodic potential: the transverse localization of light caused by random fluctuations on a two-dimensional photonic lattice. We demonstrate how ballistic transport becomes diffusive in the presence of disorder, and that crossover to Anderson localization occurs at a higher level of disorder. Finally, we study how nonlinearities affect Anderson localization. As Anderson localization is a universal phenomenon, the ideas presented here could also be implemented in other systems (for example, matter waves), thereby making it feasible to explore experimentally long-sought fundamental concepts, and bringing up a variety of intriguing questions related to the interplay between disorder and nonlinearity.     

Neurotrophin-conjugated nanoparticles prevent retina damage induced by oxidative stress

Glaucoma and other optic neuropathies are characterized by a loss of retinal ganglion cells (RGCs), a cell layer located in the posterior eye segment. Several preclinical studies demonstrate that neurotrophins (NTs) prevent RGC loss. However, NTs are rarely investigated in the clinic due to various issues, such as difficulties in reaching the retina, the very short half-life of NTs, and the need for multiple injections. We demonstrate that NTs can be conjugated to magnetic nanoparticles (MNPs), which act as smart drug carriers. This combines the advantages of the self-localization of the drug in the retina and drug protection from fast degradation. We tested the nerve growth factor and brain-derived neurotrophic factor by comparing the neuroprotection of free versus conjugated proteins in a model of RGC loss induced by oxidative stress. Histological data demonstrated that the conjugated proteins totally prevented RGC loss, in sharp contrast to the equivalent dose of free proteins, which had no effect. The overall data suggest that the nanoscale MNP-protein hybrid is an excellent tool in implementing ocular drug delivery strategies for neuroprotection and therapy.     

Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase

Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid cycle (TCA cycle) that catalyses the hydration of fumarate into malate. Germline mutations of FH are responsible for hereditary leiomyomatosis and renal-cell cancer (HLRCC). It has previously been demonstrated that the absence of FH leads to the accumulation of fumarate, which activates hypoxia-inducible factors (HIFs) at normal oxygen tensions. However, so far no mechanism that explains the ability of cells to survive without a functional TCA cycle has been provided. Here we use newly characterized genetically modified kidney mouse cells in which Fh1 has been deleted, and apply a newly developed computer model of the metabolism of these cells to predict and experimentally validate a linear metabolic pathway beginning with glutamine uptake and ending with bilirubin excretion from Fh1-deficient cells. This pathway, which involves the biosynthesis and degradation of haem, enables Fh1-deficient cells to use the accumulated TCA cycle metabolites and permits partial mitochondrial NADH production. We predicted and confirmed that targeting this pathway would render Fh1-deficient cells non-viable, while sparing wild-type Fh1-containing cells. This work goes beyond identifying a metabolic pathway that is induced in Fh1-deficient cells to demonstrate that inhibition of haem oxygenation is synthetically lethal when combined with Fh1 deficiency, providing a new potential target for treating HLRCC patients.     

Leibniz and Newton on Space

This paper reexamines the historical debate between Leibniz and Newton on the nature of space. According to the traditional reading, Leibniz (in his correspondence with Clarke) produced metaphysical arguments (relying on the Principle of Sufficient Reason and the Principle of Identity of Indiscernibles) in favor of a relational account of space. Newton, according to the traditional account, refuted the metaphysical arguments with the help of an empirical argument based on the bucket experiment. The paper claims that Leibniz’s and Newton’s arguments cannot be understood apart from the distinct dialectics of their respective positions vis-à-vis Descartes’ theory of space and physics. Against the traditional reading, the paper argues that Leibniz and Newton are operating within a different metaphysics and different conceptions of “place,” and that their respective arguments can largely remain intact without undermining the other philosopher’s conception of space. The paper also takes up the task of clarifying the distinction between true and absolute motion, and of explaining the relativity of motion implied by Leibniz’s account. The paper finally argues that the two philosophers have different conceptions of the relation between metaphysics and science, and that Leibniz’s attempt to base physical theory on an underlying metaphysical account of forces renders his account of physics unstable.     

Weak pairwise correlations imply strongly correlated network states in a neural population

Biological networks have so many possible states that exhaustive sampling is impossible. Successful analysis thus depends on simplifying hypotheses, but experiments on many systems hint that complicated, higher-order interactions among large groups of elements have an important role. Here we show, in the vertebrate retina, that weak correlations between pairs of neurons coexist with strongly collective behaviour in the responses of ten or more neurons. We find that this collective behaviour is described quantitatively by models that capture the observed pairwise correlations but assume no higher-order interactions. These maximum entropy models are equivalent to Ising models, and predict that larger networks are completely dominated by correlation effects. This suggests that the neural code has associative or error-correcting properties, and we provide preliminary evidence for such behaviour. As a first test for the generality of these ideas, we show that similar results are obtained from networks of cultured cortical neurons.     

Observation of two-dimensional discrete solitons in optically induced nonlinear photonic lattices

Nonlinear periodic lattices occur in a large variety of systems, such as biological molecules, nonlinear optical waveguides, solid-state systems and Bose-Einstein condensates. The underlying dynamics in these systems is dominated by the interplay between tunnelling between adjacent potential wells and nonlinearity. A balance between these two effects can result in a self-localized state: a lattice or 'discrete' soliton. Direct observation of lattice solitons has so far been limited to one-dimensional systems, namely in arrays of nonlinear optical waveguides. However, many fundamental features are expected to occur in higher dimensions, such as vortex lattice solitons, bright lattice solitons that carry angular momentum, and three-dimensional collisions between lattice solitons. Here, we report the experimental observation of two-dimensional (2D) lattice solitons. We use optical induction, the interference of two or more plane waves in a photosensitive material, to create a 2D photonic lattice in which the solitons form. Our results pave the way for the realization of a variety of nonlinear localization phenomena in photonic lattices and crystals. Finally, our observation directly relates to the proposed lattice solitons in Bose-Einstein condensates, which can be observed in optically induced periodic potentials.