arXiv subjects

Michele Caselle

Publications and source records attributed to Michele Caselle.

At least 55 records · Page 3Linked to original sources

arXiv2019

Hope4Genes: a Hopfield-like class prediction algorithm for transcriptomic data

After its introduction in 1982, the Hopfield model has been extensively applied for classification and pattern recognition. Recently, its great potential in gene expression patterns retrieval has also been shown. Following this line, we develop Hope4Genes a single-sample class prediction algorithm based on a Hopfield-like model. Differently from previous works, we here tested the performances of the algorithm for class prediction, a task of fundamental importance for precision medicine and therapeutic decision-making. Hope4Genes proved better performances than the state-of-art methodologies in the field independently of the size of the input dataset, its profiling platform, the number of classes and the typical class-imbalance present in biological data. Our results provide encoraging evidence that the Hopfield model, together with the use of its energy for the estimation of the false discoveries, is a particularly promising tool for precision medicine.

q-bio.QM↗

arXiv2018

Modelling the evolution of transcription factor binding preferences in complex eukaryotes

Transcription factors (TFs) exert their regulatory action by binding to DNA with specific sequence preferences. However, different TFs can partially share their binding sequences due to their common evolutionary origin. This `redundancy' of binding defines a way of organizing TFs in `motif families' by grouping TFs with similar binding preferences. Since these ultimately define the TF target genes, the motif family organization entails information about the structure of transcriptional regulation as it has been shaped by evolution. Focusing on the human TF repertoire, we show that a one-parameter evolutionary model of the Birth-Death-Innovation type can explain the TF empirical ripartition in motif families, and allows to highlight the relevant evolutionary forces at the origin of this organization. Moreover, the model allows to pinpoint few deviations from the neutral scenario it assumes: three over-expanded families (including HOX and FOX genes), a set of `singleton' TFs for which duplication seems to be selected against, and a higher-than-average rate of diversification of the binding preferences of TFs with a Zinc Finger DNA binding domain. Finally, a comparison of the TF motif family organization in different eukaryotic species suggests an increase of redundancy of binding with organism complexity.

q-bio.GN↗

arXiv2018

Continuous bunch-by-bunch spectroscopic investigation of the micro-bunching instability

Electron accelerators and synchrotrons can be operated to provide short emission pulses due to longitudinally compressed or sub-structured electron bunches. Above a threshold current, the high charge density leads to the micro-bunching instability and the formation of sub-structures on the bunch shape. These time-varying sub-structures on bunches of picoseconds-long duration lead to bursts of coherent synchrotron radiation in the terahertz frequency range. Therefore, the spectral information in this range contains valuable information about the bunch length, shape and sub-structures. Based on the KAPTURE readout system, a 4-channel single-shot THz spectrometer capable of recording 500 million spectra per second and streaming readout is presented. First measurements of time-resolved spectra are compared to simulation results of the Inovesa Vlasov-Fokker-Planck solver. The presented results lead to a better understanding of the bursting dynamics especially above the micro-bunching instability threshold.

physics.acc-ph↗

arXiv2018

Simultaneous Detection of Longitudinal and Transverse Bunch Signals at a Storage Ring

To understand and control the dynamics in the longitudinal phase space, time-resolved measurements of different bunch parameters are required. For a reconstruction of this phase space, the detector systems have to be synchronized. This reconstruction can be used e.g. for studies of the micro-bunching instability. It occurs if the interaction of the bunch with its own radiation leads to the formation of sub-structures on the longitudinal bunch profile. These sub-structures can grow rapidly -- leading to a sawtooth-like behaviour of the bunch. At KARA, we use a fast-gated intensified camera for energy spread studies, Schottky diodes for coherent synchrotron radiation studies as well as electro-optical spectral decoding for longitudinal bunch profile measurements. For a synchronization, a hardware synchronization scheme is used which compensates for eventual hardware delays. In this paper, the different experimental setups and their synchronization are discussed and first results of synchronous measurements are presented.

physics.acc-ph↗

arXiv2018

QCD thermodynamics from lattice calculations with non-equilibrium methods: The SU(3) equation of state

A precise lattice determination of the equation of state in SU(3) Yang-Mills theory is carried out by means of a simulation algorithm, based on Jarzynski's theorem, that allows one to compute physical quantities in thermodynamic equilibrium, by driving the field configurations of the system out of equilibrium. The physical results and the computational efficiency of the algorithm are compared with other state-of-the-art lattice calculations, and the extension to full QCD with dynamical fermions and to other observables is discussed.

hep-lat↗

arXiv2018

High throughput data streaming of individual longitudinal electron bunch profiles in a storage ring with single-shot electro-optical sampling

The development of fast detection methods for comprehensive monitoring of electron bunches is a prerequisite to gain comprehensive control over the synchrontron emission in storage rings with their MHz repetition rate. Here, we present a proof-of-principle experiment with at detailed description of our implementation to detect the longitudinal electron bunch profiles via single-shot, near-field electro-optical sampling at the Karlsruhe Research Accelerator (KARA). Our experiment is equipped with an ultra-fast line array camera providing a high-throughput MHz data stream. We characterize statistical properties of the obtained data set and give a detailed description for the data processing as well as for the calculation of the charge density profiles, which where measured in the short-bunch operation mode of KARA. Finally, we discuss properties of the bunch profile dynamics on a coarse-grained level on the example of the well-known synchrotron oscillation.

physics.acc-ph↗

arXiv2018

Systematic Studies of the Micro-Bunching Instability at Very Low Bunch Charges

At KARA, the KArlsruhe Research Accelerator of the KIT synchrotron, the so called short bunch operation mode allows the reduction of the bunch length down to a few picoseconds. The micro- bunching instability resulting from the high degree of longitudinal compression leads to fluctuations in the emitted THz radiation, referred to as bursting. For extremely compressed bunches at KARA, bursting occurs not only in one but in two different bunch-current ranges that are separated by a stable region. This work presents measurements of the bursting behavior in both regimes. Good agreement is found between data and numerical solutions of the Vlasov-Fokker-Planck equation.

physics.acc-ph↗

arXiv2018

Heaps' law, statistics of shared components and temporal patterns from a sample-space-reducing process

Zipf's law is a hallmark of several complex systems with a modular structure, such as books composed by words or genomes composed by genes. In these component systems, Zipf's law describes the empirical power law distribution of component frequencies. Stochastic processes based on a sample-space-reducing (SSR) mechanism, in which the number of accessible states reduces as the system evolves, have been recently proposed as a simple explanation for the ubiquitous emergence of this law. However, many complex component systems are characterized by other statistical patterns beyond Zipf's law, such as a sublinear growth of the component vocabulary with the system size, known as Heap's law, and a specific statistics of shared components. This work shows, with analytical calculations and simulations, that these statistical properties can emerge jointly from a SSR mechanism, thus making it an appropriate parameter-poor representation for component systems. Several alternative (and equally simple) models, for example based on the preferential attachment mechanism, can also reproduce Heaps' and Zipf's laws, suggesting that additional statistical properties should be taken into account to select the most-likely generative process for a specific system. Along this line, we will show that the temporal component distribution predicted by the SSR model is markedly different from the one emerging from the popular rich-gets-richer mechanism. A comparison with empirical data from natural language indicates that the SSR process can be chosen as a better candidate model for text generation based on this statistical property. Finally, a limitation of the SSR model in reproducing the empirical "burstiness" of word appearances in texts will be pointed out, thus indicating a possible direction for extensions of the basic SSR process.

cond-mat.stat-mech↗

arXiv2018

Statistics of shared components in complex component systems

Many complex systems are modular. Such systems can be represented as "component systems", i.e., sets of elementary components, such as LEGO bricks in LEGO sets. The bricks found in a LEGO set reflect a target architecture, which can be built following a set-specific list of instructions. In other component systems, instead, the underlying functional design and constraints are not obvious a priori, and their detection is often a challenge of both scientific and practical importance, requiring a clear understanding of component statistics. Importantly, some quantitative invariants appear to be common to many component systems, most notably a common broad distribution of component abundances, which often resembles the well-known Zipf's law. Such "laws" affect in a general and non-trivial way the component statistics, potentially hindering the identification of system-specific functional constraints or generative processes. Here, we specifically focus on the statistics of shared components, i.e., the distribution of the number of components shared by different system-realizations, such as the common bricks found in different LEGO sets. To account for the effects of component heterogeneity, we consider a simple null model, which builds system-realizations by random draws from a universe of possible components. Under general assumptions on abundance heterogeneity, we provide analytical estimates of component occurrence, which quantify exhaustively the statistics of shared components. Surprisingly, this simple null model can positively explain important features of empirical component-occurrence distributions obtained from data on bacterial genomes, LEGO sets, and book chapters. Specific architectural features and functional constraints can be detected from occurrence patterns as deviations from these null predictions, as we show for the illustrative case of the "core" genome in bacteria.

q-bio.GN↗

arXiv2018

Identification of microRNA clusters cooperatively acting on Epithelial to Mesenchymal Transition in Triple Negative Breast Cancer

MicroRNAs play important roles in many biological processes. Their aberrant expression can have oncogenic or tumor suppressor function directly participating to carcinogenesis, malignant transformation, invasiveness and metastasis. Indeed, miRNA profiles can distinguish not only between normal and cancerous tissue but they can also successfully classify different subtypes of a particular cancer. Here, we focus on a particular class of transcripts encoding polycistronic miRNA genes that yields multiple miRNA components. We describe clustered MiRNA Master Regulator Analysis (ClustMMRA), a fully redesigned release of the MMRA computational pipeline (MiRNA Master Regulator Analysis), developed to search for clustered miRNAs potentially driving cancer molecular subtyping. Genomically clustered miRNAs are frequently co-expressed to target different components of pro-tumorigenic signalling pathways. By applying ClustMMRA to breast cancer patient data, we identified key miRNA clusters driving the phenotype of different tumor subgroups. The pipeline was applied to two independent breast cancer datasets, providing statistically concordant results between the two analysis. We validated in cell lines the miR-199/miR-214 as a novel cluster of miRNAs promoting the triple negative subtype phenotype through its control of proliferation and EMT.

q-bio.MN↗

arXiv2018

ROPPERI - A TPC readout with GEMs, pads and Timepix

The concept of a hybrid readout of a time projection chamber is presented. It combines a GEM-based amplification and a pad-based anode plane with a pixel chip as readout electronics. This way, a high granularity enabling to identify electron clusters from the primary ionisation is achieved as well as flexibility and large anode coverage. The benefits of this high granularity, in particular for dE/dx measurements, are outlined and results of a simulation-based performance study are given. The structure of the first prototype board is discussed, including adaptions based on a very preliminary first measurement for a second production towards a proof-of-principle.

physics.ins-det↗

arXiv2017

$ξ/ξ_{2nd}$ ratio as a tool to refine Effective Polyakov Loop models

Effective Polyakov line actions are a powerful tool to study the finite temperature behaviour of lattice gauge theories. They are much simpler to simulate than the original lattice model and are affected by a milder sign problem, but it is not clear to which extent they really capture the rich spectrum of the original theories. We propose here a simple way to address this issue based on the so called second moment correlation length $ξ_{2nd}$. The ratio $ξ/ξ_{2nd}$ between the exponential correlation length and the second moment one is equal to 1 if only a single mass is present in the spectrum, and it becomes larger and larger as the complexity of the spectrum increases. Since both $ξ$ and $ξ_{2nd}$ are easy to measure on the lattice, this is a cheap and efficient way to keep track of the spectrum of the theory. As an example of the information one can obtain with this tool we study the behaviour of $ξ/ξ_{2nd}$ in the confining phase of the ($D=3+1$) $\mathrm{SU}(2)$ gauge theory and show that it is compatible with 1 near the deconfinement transition, but it increases dramatically as the temperature decreases. We also show that this increase can be well understood in the framework of an effective string description of the Polyakov loop correlator. This non-trivial behaviour should be reproduced by the Polyakov loop effective action; thus, it represents a stringent and challenging test of existing proposals and it may be used to fine-tune the couplings and to identify the range of validity of the approximations involved in their construction.

hep-lat↗

arXiv2017

The $ξ/ξ_{2nd}$ ratio as a test for Effective Polyakov Loop Actions

Effective Polyakov line actions are a powerful tool to study the finite temperature behaviour of lattice gauge theories. They are much simpler to simulate than the original (3+1) dimensional LGTs and are affected by a milder sign problem. However it is not clear to which extent they really capture the rich spectrum of the original theories, a feature which is instead of great importance if one aims to address the sign problem. We propose here a simple way to address this issue based on the so called second moment correlation length $ξ_{2nd}$. The ratio $ξ/ξ_{2nd}$ between the exponential correlation length and the second moment one is equal to 1 if only a single mass is present in the spectrum, and becomes larger and larger as the complexity of the spectrum increases. Since both $ξ_{exp}$ and $ξ_{2nd}$ are easy to measure on the lattice, this is an economic and effective way to keep track of the spectrum of the theory. In this respect we show using both numerical simulation and effective string calculations that this ratio increases dramatically as the temperature decreases. This non-trivial behaviour should be reproduced by the Polyakov loop effective action.

hep-lat↗

arXiv2017

Hagedorn spectrum and thermodynamics of SU(2) and SU(3) Yang-Mills theories

We present a high-precision lattice calculation of the equation of state in the confining phase of SU(2) Yang-Mills theory. We show that the results are described very well by a gas of massive, non-interacting glueballs, provided one assumes an exponentially growing Hagedorn spectrum. The latter can be derived within an effective bosonic closed-string model, leading to a parameter-free theoretical prediction, which is in perfect agreement with our lattice results. Furthermore, when applied to SU(3) Yang-Mills theory, this effective model accurately describes the lattice results reported by Borsányi et al. in JHEP 07 (2012) 056.

hep-lat↗

arXiv2017

The equation of state with non-equilibrium methods

Jarzynski's equality provides an elegant and powerful tool to directly compute differences in free energy in Monte Carlo simulations and it can be readily extended to lattice gauge theories to compute a large set of physically interesting observables. In this talk we present a novel technique to determine the thermodynamics of strongly-interacting matter based on this relation, which allows for a direct and efficient determination of the pressure using out-of-equilibrium Monte Carlo simulations on the lattice. We present results for the equation of state of the $\mathrm{SU}(3)$ Yang-Mills theory in the confined and deconfined phases. Finally, we briefly discuss the generalization of this method for theories with fermions, with particular focus on the equation of state of QCD.

hep-lat↗

arXiv2017

Stochastic timing in gene expression for simple regulatory strategies

Timing is essential for many cellular processes, from cellular responses to external stimuli to the cell cycle and circadian clocks. Many of these processes are based on gene expression. For example, an activated gene may be required to reach in a precise time a threshold level of expression that triggers a specific downstream process. However, gene expression is subject to stochastic fluctuations, naturally inducing an uncertainty in this threshold-crossing time with potential consequences on biological functions and phenotypes. Here, we consider such "timing fluctuations", and we ask how they can be controlled. Our analytical estimates and simulations show that, for an induced gene, timing variability is minimal if the threshold level of expression is approximately half of the steady-state level. Timing fuctuations can be reduced by increasing the transcription rate, while they are insensitive to the translation rate. In presence of self-regulatory strategies, we show that self-repression reduces timing noise for threshold levels that have to be reached quickly, while selfactivation is optimal at long times. These results lay a framework for understanding stochasticity of endogenous systems such as the cell cycle, as well as for the design of synthetic trigger circuits.

q-bio.MN↗

arXiv2016

Applications of Jarzynski's relation in lattice gauge theories

Jarzynski's equality is a well-known result in statistical mechanics, relating free-energy differences between equilibrium ensembles with fluctuations in the work performed during non-equilibrium transformations from one ensemble to the other. In this work, an extension of this relation to lattice gauge theory will be presented, along with numerical results for the $\mathbb{Z}_2$ gauge model in three dimensions and for the equation of state in $\mathrm{SU}(2)$ Yang-Mills theory in four dimensions. Then, further applications will be discussed, in particular for the Schrödinger functional and for the study of QCD in strong magnetic fields.

hep-lat↗

arXiv2016

Squared width and profile of the confining flux tube in the U(1) LGT in 3D

The dual formulation of the compact U(1) lattice gauge theory in three spacetime dimensions allows to finely study the squared width and the profile of the confining flux tube on a wide range of physical interquark distances. The results obtained in Monte Carlo simulations are compared with the predictions of the effective bosonic-string model and with the dual superconductor model. While the former fails at describing the data from a quantitative point of view, the latter is in good agreement with it. An interpretation of these results is proposed in light of the particular features of the U(1) lattice gauge theory in 3D and a comparison with non-Abelian gauge theories in four spacetime dimensions is discussed.

hep-lat↗