The arctic circle boundary and the Airy process

We prove that the, appropriately rescaled, boundary of the north polar region in the Aztec diamond converges to the Airy process. The proof uses certain determinantal point processes given by the extended Krawtchouk kernel. We also prove a version of Propp's conjecture concerning the structure of the tiling at the center of the Aztec diamond.Comment: Published at http://dx.doi.org/10.1214/009117904000000937 in the Annals of Probability (http://www.imstat.org/aop/) by the Institute of Mathematical Statistics (http://www.imstat.org

Plzf Regulates Germline Progenitor Self-Renewal by Opposing mTORC1

SummaryHyperactivity of mTORC1, a key mediator of cell growth, leads to stem cell depletion, although the underlying mechanisms are poorly defined. Using spermatogonial progenitor cells (SPCs) as a model system, we show that mTORC1 impairs stem cell maintenance by a negative feedback from mTORC1 to receptors required to transduce niche-derived signals. We find that SPCs lacking Plzf, a transcription factor essential for SPC maintenance, have enhanced mTORC1 activity. Aberrant mTORC1 activation in Plzf −/− SPCs inhibits their response to GDNF, a growth factor critical for SPC self-renewal, via negative feedback at the level of the GDNF receptor. Plzf opposes mTORC1 activity by inducing expression of the mTORC1 inhibitor Redd1. Thus, we identify the mTORC1-Plzf functional interaction as a critical rheostat for maintenance of the spermatogonial pool and propose a model whereby negative feedback from mTORC1 to the GDNF receptor balances SPC growth with self-renewal

Molecular regulation of spermatogonial stem cell renewal and differentiation

The intricate molecular and cellular interactions between spermatogonial stem cells (SSCs) and their cognate niche form the basis for life-long sperm production. To maintain long-term fertility and sustain sufficiently high levels of spermatogenesis, a delicate balance needs to prevail between the different niche factors that control cell fate decisions of SSCs by promoting self-renewal, differentiation priming or spermatogenic commitment of undifferentiated spermatogonia (A(undiff)). Previously the SSC niche was thought to be formed primarily by Sertoli cells. However, recent research has indicated that many distinct cell types within the testis contribute to the SSC niche including most somatic cell populations and differentiating germ cells. Moreover, postnatal testis development involves maturation of somatic supporting cell populations and onset of cyclic function of the seminiferous epithelium. The stochastic and flexible behavior of A(undiff) further complicates the definition of the SSC niche. Unlike in invertebrate species, providing a simple anatomical description of the SSC niche in the mouse is therefore challenging. Rather, the niche needs to be understood as a dynamic system that is able to serve the long-term reproductive function and maintenance of fertility both under steady-state and during development plus regeneration. Recent data from us and others have also shown that A(undiff) reversibly transition between differentiation-primed and self-renewing states based on availability of niche-derived cues. This review focuses on defining the current understanding of the SSC niche and the elements involved in its regulation

Design of a COTS MST distributed sensor suite system for planetary surface exploration

The aim of this project is To bring together current commercially available technology and relevant Microsystems Technology (MST) into a small, standardised spacecraft primary systems architecture, multiple units of which can demonstrate collaboration… Distributed “lab-on-a-chip” sensor networks are a possible option for the surface exploration of both Earth and Mars, and as such have been chosen as a model small spacecraft architecture. This project presents a systems approach to the design of a collection of collaborative MST sensor suites for use in a variety of environments. Based on a set of derived objectives, the main features of the study are: What are the fundamental limits to miniaturisation? What are the hardware issues raised using both standard and MST components? What is the optimum deployment pattern of the network to locate various shaped targets? What are the strategic and economic challenges of MST and the development of a sensor suite network? In general, there are few fundamental physical laws that limit the size of the sensor system. Limits tend to be driven by other factors including user requirements and the external environment. A simple breadboard model of the sensor suite consisting current COTS MST components raised practical issues such as circuit layouts, power requirements and packaging. A grid illustrating features of the Martian surface was created. Various patterns of target and sensor clusters were simulated. Overall, for larger target areas, clusters of sensors produced the best “hit rate”. The overall system utilises both wired and wireless communications methods. The I2C protocol has been investigated for intersuite communications. A link has been made between bacteria pools found on Glaciers (Cryoconites) and the possible conditions for life at the Polar Ice Caps of Mars. The investigation of Arctic Cryoconites has been selected as a representative case study that will incorporate all aspects of the project and demonstrate the system design. A comprehensive mission baseline based on this application has been produced, however the system has been designed to enable its use in a variety of situations whilst requiring only minimal modification to the overall design.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Nitrate supply and uptake in the Atlantic Arctic sea ice zone: seasonal cycle, mechanisms and drivers

Nutrient supply to the surface ocean is a key factor regulating primary production in the Arctic Ocean under current conditions and with ongoing warming and sea ice losses. Here we present seasonal nitrate concentration and hydrographic data from two oceanographic moorings on the northern Barents shelf between autumn 2017 and summer 2018. The eastern mooring was sea ice-covered to varying degrees during autumn, winter and spring, and was characterized by more Arctic-like oceanographic conditions, while the western mooring was ice-free year-round and showed a greater influence of Atlantic water masses. The seasonal cycle in nitrate dynamics was similar under ice-influenced and ice-free conditions, with biological nitrate uptake beginning near-synchronously in early May, but important differences between the moorings were observed. Nitrate supply to the surface ocean preceding and during the period of rapid drawdown was greater at the ice-free more Atlantic-like western mooring, and nitrate drawdown occurred more slowly over a longer period of time. This suggests that with ongoing sea ice losses and Atlantification, the expected shift from more Arctic-like ice-influenced conditions to more Atlantic-like ice-free conditions is likely to increase nutrient availability and the duration of seasonal drawdown in this Arctic shelf region. The extent to which this increased nutrient availability and longer drawdown periods will lead to increases in total nitrate uptake, and support the projected increases in primary production, will depend on changes in upper ocean stratification and their effect on light availability to phytoplankton as changes in climate and the physical environment proceed. This article is part of the theme issue 'The changing Arctic Ocean: consequences for biological communities, biogeochemical processes and ecosystem functioning'

CIP2A Promotes Proliferation of Spermatogonial Progenitor Cells and Spermatogenesis in Mice

Protein phosphatase 2A (PP2A) is a critical regulator of protein serine/threonine phosphorylation. However, the physiological and developmental roles of different PP2A complexes are very poorly understood. Here, we show that a newly characterized PP2A inhibitory protein CIP2A is co-expressed with ki-67 and with self-renewal protein PLZF in the spermatogonial progenitor cell (SPC) population in the testis. CIP2A and PLZF expression was shown also to correlate Ki-67 expression in human testicular spermatogonia. Functionally, CIP2A mutant mouse testes exhibited smaller number of PLZF-positive SPCs and reduced sperm counts. Moreover, seminiferous tubuli cells isolated from CIP2A mutant mice showed reduced expression of Plzf and other renewal genes Oct-4 and Nanog at mRNA level. However, PLZF-deficient testes did not show altered CIP2A expression. Importantly, spermatogonia-specific restoration of CIP2A expression rescued PLZF expression and sperm production defects observed in CIP2A mutant mice. Taken together, these results reveal first physiological function for an emerging human oncoprotein CIP2A, and provide insights into maintenance of PLZF-positive progenitors. Moreover, demonstration that CIP2A expression can be systematically inhibited without severe consequences to normal mouse development and viability may have clinical relevance regarding targeting of oncogenic CIP2A for future cancer therapies

Probing isolated compact remnants with microlensing

We consider isolated compact remnants (ICoRs), i.e. neutrons stars and black holes that do not reside in binary systems and therefore cannot be detected as X-ray binaries. ICoRs may represent $\sim\,5$ percent of the stellar mass budget of the Galaxy, but they are very hard to detect. Here we explore the possibility of using microlensing to identify ICoRs. In a previous paper we described a simulation of neutron star evolution in phase space in the Galaxy, taking into account the distribution of the progenitors and the kick at formation. Here we first reconsider the evolution and distribution of neutron stars and black holes adding a bulge component. From the new distributions we calculate the microlensing optical depth, event rate and distribution of event time scales, comparing and contrasting the case of ICoRs and "normal stars". We find that the contribution of remnants to optical depth is slightly lower than without kinematics, owing to the evaporation from the Galaxy. On the other hand, the relative contribution to the rate of events is a factor $\sim\,5$ higher. In all, $\sim\,6-7$ percent of the events are likely related to ICoRs. In particular, $\sim\,30-40$ percent of the events with duration $>\,100$ days are possibly related to black holes. It seems therefore that microlensing observations are a suitable tool to probe the population of Galactic ICoRs.Comment: 7 pages, 14 figures. Accepted for publication in Astronomy and Astrophysic

SOX3 promotes generation of committed spermatogonia in postnatal mouse testes

SOX3 is a transcription factor expressed within the developing and adult nervous system where it mostly functions to help maintain neural precursors. Sox3 is also expressed in other locations, notably within the spermatogonial stem/progenitor cell population in postnatal testis. Independent studies have shown that Sox3 null mice exhibit a spermatogenic block as young adults, the mechanism of which remains poorly understood. Using a panel of spermatogonial cell marker genes, we demonstrate that Sox3 is expressed within the committed progenitor fraction of the undifferentiated spermatogonial pool. Additionally, we use a Sox3 null mouse model to define a potential role for this factor in progenitor cell function. We demonstrate that Sox3 expression is required for transition of undifferentiated cells from a GFRα1+ self-renewing state to the NGN3 + transit-amplifying compartment. Critically, using chromatin immunoprecipitation, we demonstrate that SOX3 binds to a highly conserved region in the Ngn3 promoter region in vivo, indicating that Ngn3 is a direct target of SOX3. Together these studies indicate that SOX3 functions as a pro-commitment factor in spermatogonial stem/progenitor cells.</p