180 research outputs found
Nanoscale magnetometry through quantum control of nitrogen-vacancy centres in rotationally diffusing nanodiamonds
The confluence of quantum physics and biology is driving a new generation of
quantum-based sensing and imaging technology capable of harnessing the power of
quantum effects to provide tools to understand the fundamental processes of
life. One of the most promising systems in this area is the nitrogen-vacancy
centre in diamond - a natural spin qubit which remarkably has all the right
attributes for nanoscale sensing in ambient biological conditions. Typically
the nitrogen-vacancy qubits are fixed in tightly controlled/isolated
experimental conditions. In this work quantum control principles of
nitrogen-vacancy magnetometry are developed for a randomly diffusing diamond
nanocrystal. We find that the accumulation of geometric phases, due to the
rotation of the nanodiamond plays a crucial role in the application of a
diffusing nanodiamond as a bio-label and magnetometer. Specifically, we show
that a freely diffusing nanodiamond can offer real-time information about local
magnetic fields and its own rotational behaviour, beyond continuous optically
detected magnetic resonance monitoring, in parallel with operation as a
fluorescent biomarker.Comment: 9 pages, with 5 figure
BlinkML: Efficient Maximum Likelihood Estimation with Probabilistic Guarantees
The rising volume of datasets has made training machine learning (ML) models
a major computational cost in the enterprise. Given the iterative nature of
model and parameter tuning, many analysts use a small sample of their entire
data during their initial stage of analysis to make quick decisions (e.g., what
features or hyperparameters to use) and use the entire dataset only in later
stages (i.e., when they have converged to a specific model). This sampling,
however, is performed in an ad-hoc fashion. Most practitioners cannot precisely
capture the effect of sampling on the quality of their model, and eventually on
their decision-making process during the tuning phase. Moreover, without
systematic support for sampling operators, many optimizations and reuse
opportunities are lost.
In this paper, we introduce BlinkML, a system for fast, quality-guaranteed ML
training. BlinkML allows users to make error-computation tradeoffs: instead of
training a model on their full data (i.e., full model), BlinkML can quickly
train an approximate model with quality guarantees using a sample. The quality
guarantees ensure that, with high probability, the approximate model makes the
same predictions as the full model. BlinkML currently supports any ML model
that relies on maximum likelihood estimation (MLE), which includes Generalized
Linear Models (e.g., linear regression, logistic regression, max entropy
classifier, Poisson regression) as well as PPCA (Probabilistic Principal
Component Analysis). Our experiments show that BlinkML can speed up the
training of large-scale ML tasks by 6.26x-629x while guaranteeing the same
predictions, with 95% probability, as the full model.Comment: 22 pages, SIGMOD 201
Apoptosis-inducing factor is involved in the regulation of caspase-independent neuronal cell death
Caspase-independent death mechanisms have been shown to execute apoptosis in many types of neuronal injury. P53 has been identified as a key regulator of neuronal cell death after acute injury such as DNA damage, ischemia, and excitotoxicity. Here, we demonstrate that p53 can induce neuronal cell death via a caspase-mediated process activated by apoptotic activating factor-1 (Apaf1) and via a delayed onset caspase-independent mechanism. In contrast to wild-type cells, Apaf1-deficient neurons exhibit delayed DNA fragmentation and only peripheral chromatin condensation. More importantly, we demonstrate that apoptosis-inducing factor (AIF) is an important factor involved in the regulation of this caspase-independent neuronal cell death. Immunofluorescence studies demonstrate that AIF is released from the mitochondria by a mechanism distinct from that of cytochrome-c in neurons undergoing p53-mediated cell death. The Bcl-2 family regulates this release of AIF and subsequent caspase-independent cell death. In addition, we show that enforced expression of AIF can induce neuronal cell death in a Bax- and caspase-independent manner. Microinjection of neutralizing antibodies against AIF significantly decreased injury-induced neuronal cell death in Apaf1-deficient neurons, indicating its importance in caspase-independent apoptosis. Taken together, our results suggest that AIF may be an important therapeutic target for the treatment of neuronal injury
APAF1 is a key transcriptional target for p53 in the regulation of neuronal cell death
p53 is a transcriptional activator which has been implicated as a key regulator of neuronal cell death after acute injury. We have shown previously that p53-mediated neuronal cell death involves a Bax-dependent activation of caspase 3; however, the transcriptional targets involved in the regulation of this process have not been identified. In the present study, we demonstrate that p53 directly upregulates Apaf1 transcription as a critical step in the induction of neuronal cell death. Using DNA microarray analysis of total RNA isolated from neurons undergoing p53-induced apoptosis a 5–6-fold upregulation of Apaf1 mRNA was detected. Induction of neuronal cell death by camptothecin, a DNA-damaging agent that functions through a p53-dependent mechanism, resulted in increased Apaf1 mRNA in p53-positive, but not p53-deficient neurons. In both in vitro and in vivo neuronal cell death processes of p53-induced cell death, Apaf1 protein levels were increased. We addressed whether p53 directly regulates Apaf1 transcription via the two p53 consensus binding sites in the Apaf1 promoter. Electrophoretic mobility shift assays demonstrated p53–DNA binding activity at both p53 consensus binding sequences in extracts obtained from neurons undergoing p53-induced cell death, but not in healthy control cultures or when p53 or the p53 binding sites were inactivated by mutation. In transient transfections in a neuronal cell line with p53 and Apaf1 promoter–luciferase constructs, p53 directly activated the Apaf1 promoter via both p53 sites. The importance of Apaf1 as a p53 target gene in neuronal cell death was evaluated by examining p53-induced apoptotic pathways in primary cultures of Apaf1-deficient neurons. Neurons treated with camptothecin were significantly protected in the absence of Apaf1 relative to those derived from wild-type littermates. Together, these results demonstrate that Apaf1 is a key transcriptional target for p53 that plays a pivotal role in the regulation of apoptosis after neuronal injury
Shannon Information Theory and Molecular Biology
The role and the contribution of Shannon Information Theory to the development of Molecular Biology has been the object of stimulating debates during the last thirty years. This seems to be connected with some semantic charms associated with the use of the word \u201cinformation\u201d in the biological context. Furthermore information itself, if viewed in a broader perspective, is far from being completely defined in a fashion that overcomes the technical level at which the classical Information Theory has been conceived. This review aims at building on the acknowledged contribution of Shannon Information Theory to Molecular Biology, so as to discover if it is only a technical tool to analyze DNA and proteinic sequences, or if it can rise, at least in perspective, to a higher role that exerts an influence on the construction of a suitable model for handling the genetic information in Molecular Biology
Integrating ecology and evolutionary theory. A game changer for biodiversity conservation?
Currently, one of the central arguments in favour of biodiversity conservation is that it is essential for the maintenance of ecosystem services, that is, the benefits that people receive from ecosystems. However, the relationship between ecosystem services and biodiversity is contested and needs clarification. The goal of this chapter is to spell out the interaction and reciprocal influences between conservation science, evolutionary biology, and ecology, in order to understand whether a stronger integration of evolutionary and ecological studies might help clarify the interaction between biodiversity and ecosystem functioning as well as influence biodiversity conservation practices. To this end, the eco-evolutionary feedback theory proposed by David Post and Eric Palkovacs is analysed, arguing that it helps operationalise niche construction theory and develop a more sophisticated understanding of the relationship between ecosystem functioning and biodiversity. Finally, it is proposed that by deepening the integration of ecological and evolutionary factors in our understanding of ecosystem functioning, the eco-evolutionary feedback theory is supportive of an “evolutionary-enlightened management” of biodiversity within the ecosystem services approach.info:eu-repo/semantics/publishedVersio
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