Simple Wriggling is Hard unless You Are a Fat Hippo

We prove that it is NP-hard to decide whether two points in a polygonal domain with holes can be connected by a wire. This implies that finding any approximation to the shortest path for a long snake amidst polygonal obstacles is NP-hard. On the positive side, we show that snake's problem is "length-tractable": if the snake is "fat", i.e., its length/width ratio is small, the shortest path can be computed in polynomial time.Comment: A shorter version is to be presented at FUN 201

DNA supercoiling in bacteria: state of play and challenges from a viewpoint of physics based modeling

DNA supercoiling is central to fundamental processes of living organisms. Its average level along the chromosome and over time reflects the dynamic equilibrium of opposite activities of topoisomerases, which are required to relax mechanical stresses that are inevitably produced during DNA replication and gene transcription. Supercoiling affects all scales of the spatio-temporal organization of bacterial DNA, from the base pair to the large scale chromosome conformation. Highlighted in vitro and in vivo in the 1960s and 1970s, respectively, the first physical models were proposed concomitantly in order to predict the deformation properties of the double helix. About fifteen years later, polymer physics models demonstrated on larger scales the plectonemic nature and the tree-like organization of supercoiled DNA. Since then, many works have tried to establish a better understanding of the multiple structuring and physiological properties of bacterial DNA in thermodynamic equilibrium and far from equilibrium. The purpose of this essay is to address upcoming challenges by thoroughly exploring the relevance, predictive capacity, and limitations of current physical models, with a specific focus on structural properties beyond the scale of the double helix. We discuss more particularly the problem of DNA conformations, the interplay between DNA supercoiling with gene transcription and DNA replication, its role on nucleoid formation and, finally, the problem of scaling up models. Our primary objective is to foster increased collaboration between physicists and biologists. To achieve this, we have reduced the respective jargon to a minimum and we provide some explanatory background material for the two communities.Comment: 11 figure

Developmental dynamics of the epigenome and methods to find relevant regulatory motifs

Studying the epigenome and which transcription factors interact with it gives us a better understanding of how developmental processes are regulated and harmoniously orchestrated. For sensory neurons, such signals correspond to environmental stimuli. A group of genes called immediate early genes (IEGs) are known to play important roles during development, and they are some of the first to respond to signals a cell receives. They tend to encode for transcription factors (TFs), are activated within minutes and regulate the activity of other genes. Studying the features of these genes, we found a new epigenetic signature that hints at why they can be induced so fast. They have the active H3K27ac mark on their promoters, and the repressive H3K27me3 mark on their gene bodies. We found a few hundred genes with this signature and called them ‘bipartite’ genes. Bipartite genes are very lowly expressed, or not at all. They are, however, in a poised state that is even more ready to be quickly induced than the known bivalent genes. The needed transcriptional machinery is already sitting at the promoter. We used t-distributed stochastic neighbor embedding to jointly visualize chromatin accessibility and several histone marks on all genes in barrelette neurons of the somatosensory system in mice. Moreover, we used several developmental time points to visualize genome-wide changes in chromatin states across development. This allowed us to visualize the epigenetic dynamics that bipartite genes undergo by observing how they move from one developmental time point to another in these chromatin landscapes. As mentioned, IEGs correspond to TFs that have important regulatory roles. Knowing which TFs play relevant or functional roles is key to understanding the underlying developmental processes. Motivated by the importance of finding relevant TFs, we developed computational methods that enable us to make predictions, in an unbiased way, about which TFs could explain an experimental measure of interest, typically coming from sequencing data. We created an R package called monaLisa, short for “motif analysis with Lisa”, that allows for these methods to be used in a user-friendly manner. The package offers two main ways of identifying regulatory motifs. In the first approach, we made use of an existing method of correcting for sequence composition differences to apply a binned motif enrichment analysis. This method links motif enrichment to an experimental value, for example changes in DNA methylation between two conditions. The second approach uses linear regression to select a set of TFs that are likely to explain the given observations. Specifically, we use randomized lasso stability selection to discover relevant motifs. The new epigenetic signature with the bipartite genes illustrates how the epigenome can control a timely transcriptional response during development, and the methods in monaLisa further enable us to decipher which TFs could be key players

Generating chromosome geometries in a minimal cell from cryo-electron tomograms and chromosome conformation capture maps

Macromolecular Biochemistr

In Silico Analysis of Advanced Processing Methods for Light-weight Alloys Powders

Light-weight Al and Mg-based metal-matrix nanocomposites (MMNCs) are lauded as one of the most promising structural materials for vehicle, military, and construction applications. These MMNCs are often synthesized using the powder metallurgy (PM) process under liquid nitrogen cryogenic environments to control the grain sizes. It is believed that proper incorporation of the nitrogen species into the bulk lattice during processing could strongly enhance the mechanical properties of MMNCs by forming N-rich dispersoids. In this work, using the density-functional theory (DFT), the adsorption, absorption and diffusion behavior of nitrogen molecule/atoms have been studied and related to t Al and Mg MMNC PM processing. The study includes the impacts of binding sites, alloying elements (Al, Zn, and Y in Mg and Mg, Mn and Fe for Al), and surface crystallographic planes on the nitrogen molecule adsorption energies. The transition state (TS) behaviors for the bond breaking and lattice diffusion of nitrogen were examined. The results show that in presence of Mg (0001) or Al (111) surfaces, dissociation of $N_2$ to N atoms requires 1/9 to 1/5 of the isolated state energy , respectively. As a critical issue limiting the application of Mg-based MMNCs, the degradation (corrosion) of Mg alloys in aqueous media was modeled in this work. It is known that both the internal crystal structures and the impurity compositions/contents in the Mg alloys can affect the degradation rates. Density-functional theory (DFT) computation was utilized to understand the surface degradation behaviors with different crystallographic orientations and impurity elements from an atomistic standpoint. The adsorption response of the Mg alloy surface to the water molecule and the dissolution of surface atoms were studied to describe the degradation behavior of Mg and Mg alloys. The tendency for water molecule adsorption was quantified for Mg-based slab systems with low-index surface planes and various alloying elements including Al, Zn, Ca, and Y. The trends for surface degradation from these systems were examined using surface energy analysis and electrode potential shift analysis. The results showed that adding Ca and/or Y increases the propensity to attract a water molecule to the alloy surface. Also, it was generally found that the relative electrode potential shift of Mg-Y alloys is positive while those of all other alloys are negative. After having a comprehensive understanding about the atomistic behavior of metal powder in contact with the cryomilling media, the consolidation process was analyzed, including the melting and resolidification of powder through selective laser melting. At this stage of the work the concerns were to achieve the maximum connectivity between the powder layers after resolidification and to avoid extreme superheat. Since the efficiency of the MMNCs strongly relies on homogeneous distribution of reinforcement particles the SLM process was optimized to avoid any clustering of the reinforcement particles. Focusing on consolidation of MMNCS, Al10SiMg/AlN with weight ratio of 99:1 was chosen. AlSi10Mg with $10\%$ Si and $0.5\%$ Mg is one the most convenient compositions among the light weight alloys for laser melting processes, due to its narrow solidification range, that provides sufficient fluidity to produce sound products. Also, as the powder had been prepared via cryomilling process, the presence of AlN particles was proven based on the DFT calculations and experimental evidence described earlier. The laser power, scanning velocity and initial temperature of the powder were selected as the most important factors affecting the melting and solidification of the alloy powder. Finite volume analysis and experimental design were applied to optimize the SLM processing condition. Finite volume method was used to estimate the melt pool geometry, temperature profile of the part and velocity of solidification front. This information is necessary to produce strong parts with homogeneous properties all over the specimen, minimize energy consumption and avoid formation of defects in the sample. It was confirmed that even in the most extreme conditions the maximum temperature during the process would not exceed 1710K, which is roughly 460K below the melting temperature of the AlN reinforcement particles. The laser speed and power have significant effect on the melt pool geometry and maximum temperature of melt pool while the effect of initial powder temperature was insignificant for both of the response values. The AlN reinforcement particles are expected to have a homogeneous distribution since the velocity of the solidification front is higher than the critical calculated value of 5900 $\mu$ m/s. Results also showed that the solidification front velocity depends on the laser speed and the effects of laser power and initial temperature are insignificant. This work provides a comprehensive multiscale computational model tracking the Al and Mg based light-weight alloys from powder preparation stage to shaping the final product that considers potential gaps with focus on solidification process. These findings are particularly important to eliminate the extra processing steps to save time, energy and material maintaining the high quality of the final product

Towards A Unified Model Of Sperm Chromatin Structure

Sperm possess several layers of information that are delivered to the oocyte alongside the paternal DNA. Examples of potential sperm borne molecular cues of probable use to the embryo include RNAs and local and global chromatin structure. To identify candidate sperm RNAs that likely reach the oocyte cytoplasm following fertilization patterns of transcript compartmentalization in the mature gamete were identified. Though all sperm RNAs exhibited a preferential peripheral enrichment, a subset of RNAs were identified in which this trend was reduced. These RNAs are thought to be embedded with perinuclear theca and are correlated with late spermatogenic transcription. Malat1, a well-known nuclear non-coding RNAs, was relatively abundant within the intra-nuclear compartment of the gamete although enriched within the sperm extra-nuclear compartment. If these transcript are localized to the condensed sperm nucleus Maltat1 may contribute to the retention of somatic-like chromatin structures following nuclear remodeling. Histone-bound regions which persist in mature sperm are of interest as they may be informative of past spermatogenic and future embryonic genomic regulation. Genome wide nucleosome mapping in mature mouse sperm was complimented with a nuclease foot printing approach to identify sites of factor retention throughout the paternal gamete. Applying this analysis to a transgenic mouse model harboring the human protamine locus, highlighted the potential regulatory impact of the chromatin environment at the local and domain level. Consideration of these results within the context of the endogenous mouse protamine locus identified a candidate transcriptional regulatory mechanism. Factors predicted to be bound in mature sperm were correlated with genomic elements utilized in the testis and the very early embryo. This included Ctcf, which was significantly enriched within the boundary regions of topologically associated domains and the promoter regions of genes expressed in the zygote. These patterns were not observed in human or bull sperm. It is suggested that delivery of the paternal genome in association with regulatory factors may reflect the accelerated preimplantation development of the murine embryo. Sites of Ctcf retention in mature sperm were considered within a novel model of spermatogenic nuclear remodeling

Earthworms, flooding, and sewage sludge

Earthworms are ecosystem engineers. Their burrowing increases soil water holding capacity, changes microbial populations, and improves soil nutrient content. In the UK, flooding is predicted to increase with climate change, and it is important to understand how increased flooding may affect earthworm populations. Increases in flooding may also impact soils amended with sewage sludge. The use of sewage sludge as a soil amendment increases soil organic matter content, but the interaction between sludge amendment and flooding is not understood. Oxygen concentrations of flooded soils rapidly decrease as the soil microbial community breaks down soil organic matter. This thesis examined whether sewage sludge amendment of soil led to faster rates of oxygen depletion in flooded soils, and how this could affect earthworm populations. Earthworm populations in pasture and crop fields known to regularly flood were surveyed every three months, and soil environmental factors measured. Populations subject to the stresses of both crop growth and flooding were lower than in pasture soils, with both fields dominated by the species Allolobophora chlorotica. Laboratory experiments investigating oxygen concentration depletion in flooded soil amended with sludge found little effect of sludge application on oxygen depletion; an unexpected result likely caused by the recalcitrant nature of sewage sludge. Experiments examining the oxygen requirements of some earthworm species found that the green morph of A. chlorotica appeared to aestivate in response to low oxygen conditions: a novel finding suggesting a mechanism for their survival in regularly flooded areas. Experiments examining how earthworms, flooding, and sewage sludge affected soil emissions of greenhouse gases found high emissions of N2O from unflooded soils treated with both earthworms and sewage sludge. The findings provide insight into earthworm responses to flooding at both the individual and population level, and increase understanding of interactions between earthworms, flooding, and sewage sludge

Mitigating autogenous shrinkage of Ultra-High Performance Concrete by means of internal curing using superabsorbent polymers

Application of smart curing concept called internal curing (IC) is the most promising strategy for mitigating autogenous shrinkage and related early-age cracking in cement-based materials with low water-to-cement ratio. There are still many theoretical and practical questions that need to be answered before IC could become a standard method. Many of these questions concern the most appealing of water-regulating additives for IC called Superabsorbent Polymers (SAP). The clear linkage between SAP material properties, the moment of water release and the effect on autogenous shrinkage is still missing, which blocks formulating recommendations for use of particular potential IC agents in concrete construction. In this treatise various aspects that are decisive for effectiveness of IC in mitigating autogenous shrinkage were examined. The choice of materials was purposefully limited to two compositions of Ultra-High Performance Concrete (UHPC), one fine-grained and one coarse-grained mixture, and one particular, in-depth characterized SAP. The objectives of examination which shaped the final experimental programme were: assessment of IC agent absorption capacity, specification of periods of water migration from fresh concrete mixture into SAP and from SAP back into hardening concrete, determination of effect of SAP addition on cement hydration, evaluation of IC influence on and determination of start of effective autogenous shrinkage and, finally, assessment of autogenous shrinkage with selfsame IC agent but for different matrices. Ideally, description of the mechanisms behind the action of IC at different stages of concrete life and reasoning of differences observed for the UHPCs under investigation had to be provided. First, the main components of the system – UHPC and SAP material – were characterized as to their suitability for IC application. Special attention was paid to the material properties which affect water transport. Usage of different testing methods was necessary here and included: testing with ESEM, FT-IR, tea-bag test, sol fraction content examination and X-ray computed tomography (for SAP) as well as air content measurement and various methods for characterization of the porosity and other features of the microstructure. The observed delay in the start of pozzolanic reactions in case of fine-grained UHPC was rather surprising, but, under consideration of porosity, shed new light on permeability of young UHPC. The work at hand revealed numerous methods that can be used for studying the absorption capacity of polymers, but hardly representative for the behaviour of those polymers within concrete matrix. Because of its general availability and the relatively robust testing procedure, it was decided to focus on possibilities and limitations of using tea-bag test for evaluation of absorption capacity of SAP. New interpretation of tea-bag test results was deduced which enabled assessment of maximum absorption capacity of SAP from measurement of consistency of concrete before and after modification with IC. Influence of IC on hydration process was revealed by using two non-destructive methods, in particular ultrasonic measurement and concrete temperature record. It could be shown that the ionic polymer exhibits complex effects including retardation and acceleration of individual chemical processes. Additionally, X-ray computed tomography (CT) and instrumented ring tests were performed in order to understand scientific significance of the characteristic event appearing during shrinkage measurements, taken as time-zero (= starting point for evaluation of autogenous shrinkage data). Linkage of time-zero with certain phenomenon, e.g., changes of the SAP particles volume or specific value of yield stress, but not with final set, was suggested for the future investigations. By using two setups based on corrugated tube protocol it was possible to register and compare autogenous shrinkage of both UHPCs without and with modification by IC. The effectiveness of IC was shown to be dependent on the matrix in which IC was implemented. This was related to the observed changes in pore percolation that resulted from different absorption behaviour of SAP in the two UHPCs under investigation. Furthermore, the effect of fibres on effectiveness of IC was discussed. Description and discussion of mechanisms behind IC was supported by measurement of capillary pressure, total shrinkage tests with simultaneous mass loss measurement, free autogenous shrinkage tests and the CT measurement. Valuable source of information was furthermore the in-depth literature review. The most appealing finding of the work and the biggest paradox revealed was high efficiency of IC in mitigating autogenous shrinkage and simultaneously appearance of stage where very clear reverse in mode of polymer volume change was observed. This suggests partial reabsorption of water initially released. This puts interpretation of operative shrinkage mechanisms and ones standing behind IC effect in a new perspective.Die innere Nachbehandlung (Internal Curing – IC) ist die derzeit aussichtsreichste Strategie, um das in zementgebundenen Baustoffen mit niedrigen Wasser/Zement-Werten ausgeprägt auftretende autogene Schwinden wirksam zu verringern und die damit einhergehende Rissbildung in jungem Beton zu vermeiden. Vor einer breiten baupraktischen Anwendung des IC sind noch viele offene Fragen zu beantworten. Die meisten dieser Fragen betreffen die derzeit interessanteste Klasse von wasserregulierenden Stoffen für das IC – die superabsorbierenden Polymere (SAP). Von entscheidender Bedeutung ist hier der noch weitgehend unerforschte Zusammenhang zwischen den Materialeigenschaften der SAP, dem Zeitpunkt der Wasserabgabe und der Auswirkung auf das autogene Schwinden. In der vorliegenden Arbeit werden verschiedene Einflussfaktoren auf die Wirksamkeit von SAP zur Verringerung des autogenen Schwindens untersucht. Für die Experimente wurde ein feinkörniger und ein grobkörniger ultra-hochfester Beton (UHPC) sowie ein schon detailliert charakterisiertes SAP genutzt. Das experimentelle Programm wurde auf folgende Untersuchungsziele ausgerichtet: Absorptionsvermögen der SAP, Zeitfenster der Wassermigration aus dem Frischbeton in das SAP sowie vom SAP in den erhärtenden Beton, autogenes Schwindmaß sowie effektiver Beginn des autogenen Schwindens. Ziel der Arbeiten ist die Beschreibung der Mechanismen, die IC zugrundliegen – und dies zu verschiedenen Betonaltern und unter Berücksichtigung der an den untersuchten UHPC beobachteten Unterschiede. Bei der Charakterisierung der Hauptkomponenten des betrachteten Systems – UHPC und SAP – wurde auf die Materialeigenschaften fokussiert, die den Wassertransport beeinflussen. Dazu wurden u. a. folgende Untersuchungsmethoden angewendet: ESEM, FT-IR, Teebeuteltest, Sol-Fraction Test, Röntgentomographie (für SAP) sowie verschiedene Verfahren zur Charakterisierung der Poren im Beton. Im feinkörnigen UHPC wurde überraschenderweise ein verzögerter Beginn der puzzolanischen Reaktion festgestellt, der bei Berücksichtigung der vorliegenden Porosität zu einer Neubewertung der Permeabilität von UHPC in jungem Alter führte. In der vorliegenden Arbeit werden verschiedene Methoden zur Beschreibung des Wasserabsorptionsvermögens von SAP benannt, deren Aussagekraft bei Anwendung dieser Polymere im Beton aber sehr eingeschränkt ist. Aufgrund seiner einfachen Verfügbarkeit und Robustheit wurde daher der Teebeutetest zur Bestimmung der Wasserabsorption des SAP genutzt. Die Wasserabsorption der SAP im Beton wurde durch Gegenüberstellung von Konsistenzmessungen am Beton vor und nach Zugabe von SAP und Ergebnissen der Teebeuteltest abgeschätzt. Der Einfluss des IC auf die Hydratation wurde zerstörungsfrei mit Ultraschall- und Betontemperaturmessungen erfasst. Auf dieser Grundlage konnten Hypothesen zu den komplexen Wechselwirkungen zwischen ionischem Polymer und der Beschleunigung oder Verzögerung einzelner chemischer Prozesse formuliert werden. Mit Hilfe von instrumentierten Ringversuchen und X-ray Computertomographie wurden die Auswirkungen des IC mit SAP auf das autogene Schwinden, den Aufbau von Zwangsspannungen bei behindertem Schwinden und Time-Zero diskutiert. Dabei konnte ein Zusammenhang zwischen Time-Zero und verschiedenen Phänomenen, wie z. B. Volumenänderung des SAP oder der Fließgrenze des erhärtenden Betons, nicht aber zum Ende des Erstarrens aufgezeigt werden. Das autogene Schwinden beider untersuchter UHPC (jeweils mit und ohne IC) wurde mit Hilfe von Corrugated Tube-Versuchen gemessen. Es konnte gezeigt werden, dass wie Wirksamkeit des IC von der Betonzusammensetzung sowie der in den UHPC infolge Wechselwirkungen mit den SAP verschieden ausgebildeten Porenstruktur der Matrix abhängt. Weiterhin konnte ein Einfluss von Faserzugaben auf die Wirksamkeit des IC gezeigt werden. Die Beschreibung und Diskussion der Mechanismen des IC wurde durch Messungen des Kapillardrucks, des Gesamtschwindens, des freien autogenen Schwindens, des Masseverlustes und Computertomographie unterstützt. Eine wichtige Erkenntnisquelle war zudem die umfangreich gesichtete und diskutierte Literatur. Das interessanteste und zugleich paradoxe Ergebnis der Untersuchungen ist die Tatsache, dass die bei Einsatz von SAP beobachtete Verringerung des autogenen Schwindens eindeutig mit einer zeitgleichen Umkehr der Volumenänderung der SAP einhergeht: die bis dahin dominierende Wasserabgabe geht in eine erneute Wasseraufnahme über. Dies stellt die Interpretation der Triebkräfte des Schwindens und die dem IC zugrundliegenden Mechanismen in einen neuen Zusammenhang