On the mean-field spherical model

Exact solutions are obtained for the mean-field spherical model, with or without an external magnetic field, for any finite or infinite number N of degrees of freedom, both in the microcanonical and in the canonical ensemble. The canonical result allows for an exact discussion of the loci of the Fisher zeros of the canonical partition function. The microcanonical entropy is found to be nonanalytic for arbitrary finite N. The mean-field spherical model of finite size N is shown to be equivalent to a mixed isovector/isotensor sigma-model on a lattice of two sites. Partial equivalence of statistical ensembles is observed for the mean-field spherical model in the thermodynamic limit. A discussion of the topology of certain state space submanifolds yields insights into the relation of these topological quantities to the thermodynamic behavior of the system in the presence of ensemble nonequivalence.Comment: 21 pages, 5 figure

Therapeutic ultrasound as a potential male contraceptive: power, frequency and temperature required to deplete rat testes of meiotic cells and epididymides of sperm determined using a commercially available system

<p>Abstract</p> <p>Background</p> <p>Studies published in the 1970s by Mostafa S. Fahim and colleagues showed that a short treatment with ultrasound caused the depletion of germ cells and infertility. The goal of the current study was to determine if a commercially available therapeutic ultrasound generator and transducer could be used as the basis for a male contraceptive.</p> <p>Methods</p> <p>Sprague-Dawley rats were anesthetized and their testes were treated with 1 MHz or 3 MHz ultrasound while varying power, duration and temperature of treatment.</p> <p>Results</p> <p>We found that 3 MHz ultrasound delivered with 2.2 Watt per square cm power for fifteen minutes was necessary to deplete spermatocytes and spermatids from the testis and that this treatment significantly reduced epididymal sperm reserves. 3 MHz ultrasound treatment reduced total epididymal sperm count 10-fold lower than the wet-heat control and decreased motile sperm counts 1,000-fold lower than wet-heat alone. The current treatment regimen provided nominally more energy to the treatment chamber than Fahim's originally reported conditions of 1 MHz ultrasound delivered at 1 Watt per square cm for ten minutes. However, the true spatial average intensity, effective radiating area and power output of the transducers used by Fahim were not reported, making a direct comparison impossible. We found that germ cell depletion was most uniform and effective when we rotated the therapeutic transducer to mitigate non-uniformity of the beam field. The lowest sperm count was achieved when the coupling medium (3% saline) was held at 37 degrees C and two consecutive 15-minute treatments of 3 MHz ultrasound at 2.2 Watt per square cm were separated by 2 days.</p> <p>Conclusions</p> <p>The non-invasive nature of ultrasound and its efficacy in reducing sperm count make therapeutic ultrasound a promising candidate for a male contraceptive. However, further studies must be conducted to confirm its efficacy in providing a contraceptive effect, to test the result of repeated use, to verify that the contraceptive effect is reversible and to demonstrate that there are no detrimental, long-term effects from using ultrasound as a method of male contraception.</p

Janus II: a new generation application-driven computer for spin-system simulations

This paper describes the architecture, the development and the implementation of Janus II, a new generation application-driven number cruncher optimized for Monte Carlo simulations of spin systems (mainly spin glasses). This domain of computational physics is a recognized grand challenge of high-performance computing: the resources necessary to study in detail theoretical models that can make contact with experimental data are by far beyond those available using commodity computer systems. On the other hand, several specific features of the associated algorithms suggest that unconventional computer architectures, which can be implemented with available electronics technologies, may lead to order of magnitude increases in performance, reducing to acceptable values on human scales the time needed to carry out simulation campaigns that would take centuries on commercially available machines. Janus II is one such machine, recently developed and commissioned, that builds upon and improves on the successful JANUS machine, which has been used for physics since 2008 and is still in operation today. This paper describes in detail the motivations behind the project, the computational requirements, the architecture and the implementation of this new machine and compares its expected performances with those of currently available commercial systems.Comment: 28 pages, 6 figure

Murid herpesvirus-4 lacking thymidine kinase reveals route-dependent requirements for host colonization

Gammaherpesviruses infect at least 90 % of the world's population. Infection control is difficult, in part because some fundamental features of host colonization remain unknown, for example whether normal latency establishment requires viral lytic functions. Since human gammaherpesviruses have narrow species tropisms, answering such questions requires animal models. Murid herpesvirus-4 (MuHV-4) provides one of the most tractable. MuHV-4 genomes delivered to the lung or peritoneum persist without lytic replication. However, they fail to disseminate systemically, suggesting that the outcome is inoculation route-dependent. After upper respiratory tract inoculation, MuHV-4 infects mice without involving the lungs or peritoneum. We examined whether host entry by this less invasive route requires the viral thymidine kinase (TK), a gene classically essential for lytic replication in terminally differentiated cells. MuHV-4 TK knockouts delivered to the lung or peritoneum were attenuated but still reached lymphoid tissue. In contrast, TK knockouts delivered to the upper respiratory tract largely failed to establish a detectable infection. Therefore TK, and by implication lytic replication, is required for MuHV-4 to establish a significant infection by a non-invasive route

The Repeatability of Adaptive Radiation During Long-Term Experimental Evolution of Escherichia coli in a Multiple Nutrient Environment

Adaptive radiations occur when a species diversifies into different ecological specialists due to competition for resources and trade-offs associated with the specialization. The evolutionary outcome of an instance of adaptive radiation cannot generally be predicted because chance (stochastic events) and necessity (deterministic events) contribute to the evolution of diversity. With increasing contributions of chance, the degree of parallelism among different instances of adaptive radiations and the predictability of an outcome will decrease. To assess the relative contributions of chance and necessity during adaptive radiation, we performed a selection experiment by evolving twelve independent microcosms of Escherichia coli for 1000 generations in an environment that contained two distinct resources. Specialization to either of these resources involves strong trade-offs in the ability to use the other resource. After selection, we measured three phenotypic traits: 1) fitness, 2) mean colony size, and 3) colony size diversity. We used fitness relative to the ancestor as a measure of adaptation to the selective environment; changes in colony size as a measure of the evolution of new resource specialists because colony size has been shown to correlate with resource specialization; and colony size diversity as a measure of the evolved ecological diversity. Resource competition led to the rapid evolution of phenotypic diversity within microcosms. Measurements of fitness, colony size, and colony size diversity within and among microcosms showed that the repeatability of adaptive radiation was high, despite the evolution of genetic variation within microcosms. Consistent with the observation of parallel evolution, we show that the relative contributions of chance are far smaller and less important than effects due to adaptation for the traits investigated. The two-resource environment imposed similar selection pressures in independent populations and promoted parallel phenotypic adaptive radiations in all independently evolved microcosms

Out of Sight but Not out of Mind: Alternative Means of Communication in Plants

Current knowledge suggests that the mechanisms by which plants communicate information take numerous forms. Previous studies have focussed their attention on communication via chemicals, contact and light; other methods of interaction between plants have remained speculative. In this study we tested the ability of young chilli plants to sense their neighbours and identify their relatives using alternative mechanism(s) to recognised plant communication pathways. We found that the presence of a neighbouring plant had a significant influence on seed germination even when all known sources of communication signals were blocked. Furthermore, despite the signalling restriction, seedlings allocated energy to their stem and root systems differently depending on the identity of the neighbour. These results provide clear experimental evidence for the existence of communication channels between plants beyond those that have been recognized and studied thus far

Discrepant Prevalence and Incidence of Leishmania Infection between Two Neighboring Villages in Central Mali Based on Leishmanin Skin Test Surveys

Leishmaniasis is a vector-borne disease transmitted to humans by the bite of an infected sand fly. Leishmaniasis is present in more than 88 countries and affects more than 12 million people. Depending on the species of Leishmania, the host can develop cutaneous leishmaniasis (CL), which is characterized by skin ulcers in uncovered parts of the body or a more severe form, visceral leishmaniasis, which affects the liver and spleen and is fatal if not treated. This study aims to establish the past and present infection with Leishmania parasites in two villages where recent cases have been diagnosed by the dermatology center (CNAM) in Bamako. This was achieved using a Leishmania-specific skin test that was administered annually to permanent residents of Kemena and Sougoula villages from 2006 to 2008. The results show that transmission of Leishmania is active and stable in these two villages. Moreover, despite sharing similar cultural and environmental features, the individuals from Kemena presented three times the risk of Leishmania infection compared with those from Sougoula. Our findings raise awareness of the continued presence of CL in Mali

Synthetic recording and in situ readout of lineage information in single cells

Reconstructing the lineage relationships and dynamic event histories of individual cells within their native spatial context is a long-standing challenge in biology. Many biological processes of interest occur in optically opaque or physically inaccessible contexts, necessitating approaches other than direct imaging. Here, we describe a new synthetic system that enables cells to record lineage information and event histories in the genome in a format that can be subsequently read out in single cells in situ. This system, termed Memory by Engineered Mutagenesis with Optical In situ Readout (MEMOIR), is based on a set of barcoded recording elements termed scratchpads. The state of a given scratchpad can be irreversibly altered by Cas9-based targeted mutagenesis, and read out in single cells through multiplexed single-molecule RNA fluorescence hybridization (smFISH). To demonstrate a proof of principle of MEMOIR, we engineered mouse embryonic stem (ES) cells to contain multiple scratchpads and other recording components. In these cells, scratchpads were altered in a progressive and stochastic fashion as cells proliferated. Analysis of the final states of scratchpads in single cells in situ enabled reconstruction of the lineage trees of cell colonies. Combining analysis of endogenous gene expression with lineage reconstruction in the same cells further allowed inference of the dynamic rates at which ES cells switch between two gene expression states. Finally, using simulations, we showed how parallel MEMOIR systems operating in the same cell can enable recording and readout of dynamic cellular event histories. MEMOIR thus provides a versatile platform for information recording and in situ, single cell readout across diverse biological systems

Natural History of Liver Disease in a Large International Cohort of Children with Alagille syndrome:Results from The GALA Study

BACKGROUND: Alagille syndrome (ALGS) is a multisystem disorder, characterized by cholestasis. Existing outcome data are largely derived from tertiary centers and real-world data are lacking. This study aimed to elucidate the natural history of liver disease in a contemporary, international, cohort of children with ALGS.METHODS: Multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born Jan-1997 - Aug-2019. Native liver survival (NLS) and event-free survival rates were assessed. Cox models were constructed to identify early biochemical predictors of clinically evident portal hypertension (CEPH) and NLS.RESULTS: 1433 children (57% male) from 67 centers in 29 countries were included. 10 and 18-years NLS rates were 54.4% and 40.3%. By 10 and 18-years, 51.5% and 66.0% of ALGS children experienced ≥1 adverse liver-related event (CEPH, transplant or death). Children (&gt;6 and ≤12 months) with median total bilirubin (TB) levels between ≥5.0 and &lt;10.0 mg/dL had a 4.1-fold (95% CI 1.6 - 10.8) and those ≥10.0 mg/dL had an 8.0-fold (95% CI 3.4 - 18.4) increased risk of developing CEPH compared with those &lt;5.0 mg/dL. Median TB levels between ≥5.0 and &lt;10.0 mg/dL and &gt;10.0 mg/dL were associated with a 4.8 (95% CI 2.4 - 9.7) and 15.6 (95% CI 8.7 - 28.2) increased risk of transplantation relative to &lt;5.0 mg/dL. Median TB &lt;5.0 mg/dL were associated with higher NLS rates relative to ≥5.0 mg/dL, with 79% reaching adulthood with native liver (p&lt;0.001).CONCLUSIONS: In this large international cohort of ALGS, only 40.3% of children reach adulthood with their native liver. A TB &lt;5.0 mg/dL between 6-and-12-months of age is associated with better hepatic outcomes. These thresholds provide clinicians with an objective tool to assist with clinical decision-making and in the evaluation of novel therapies.</p

Ancient DNA from Hunter-Gatherer and Farmer Groups from Northern Spain Supports a Random Dispersion Model for the Neolithic Expansion into Europe

Background/Principal Findings: The phenomenon of Neolithisation refers to the transition of prehistoric populations from a hunter-gatherer to an agro-pastoralist lifestyle. Traditionally, the spread of an agro-pastoralist economy into Europe has been framed within a dichotomy based either on an acculturation phenomenon or on a demic diffusion. However, the nature and speed of this transition is a matter of continuing scientific debate in archaeology, anthropology, and human population genetics. In the present study, we have analyzed the mitochondrial DNA diversity in hunter-gatherers and first farmers from Northern Spain, in relation to the debate surrounding the phenomenon of Neolithisation in Europe. Methodology/Significance: Analysis of mitochondrial DNA was carried out on 54 individuals from Upper Paleolithic and Early Neolithic, which were recovered from nine archaeological sites from Northern Spain (Basque Country, Navarre and Cantabria). In addition, to take all necessary precautions to avoid contamination, different authentication criteria were applied in this study, including: DNA quantification, cloning, duplication (51 % of the samples) and replication of the results (43 % of the samples) by two independent laboratories. Statistical and multivariate analyses of the mitochondrial variability suggest that the genetic influence of Neolithisation did not spread uniformly throughout Europe, producing heterogeneous genetic consequences in different geographical regions, rejecting the traditional models that explain the Neolithisation in Europe