Th1 not Th17 cells drive spontaneous MS-like disease despite a functional regulatory T cell response

Multiple sclerosis is considered a disease of complex autoimmune etiology, yet there remains a lack of consensus as to specific immune effector mechanisms. Recent analyses of experimental autoimmune encephalomyelitis, the common mouse model of multiple sclerosis, have investigated the relative contribution of Th1 and Th17 CD4 T cell subsets to initial autoimmune central nervous system (CNS) damage. However, inherent in these studies are biases influenced by the adjuvant and toxin needed to break self-tolerance. We investigated spontaneous CNS disease in a clinically relevant, humanized, T cell receptor transgenic mouse model. Mice develop spontaneous, ascending paralysis, allowing unbiased characterization of T cell immunity in an HLA-DR15-restricted T cell repertoire. Analysis of naturally progressing disease shows that IFN?(+) cells dominate disease initiation with IL-17(+) cells apparent in affected tissue only once disease is established. Tregs accumulate in the CNS but are ultimately ineffective at halting disease progression. However, ablation of Tregs causes profound acceleration of disease, with uncontrolled infiltration of lymphocytes into the CNS. This synchronous, severe disease allows characterization of the responses that are deregulated in exacerbated disease: the correlation is with increased CNS CD4 and CD8 IFN? responses. Recovery of the ablated Treg population halts ongoing disease progression and Tregs extracted from the central nervous system at peak disease are functionally competent to regulate myelin specific T cell responses. Thus, in a clinically relevant mouse model of MS, initial disease is IFN? driven and the enhanced central nervous system responses unleashed through Treg ablation comprise IFN? cytokine production by CD4 and CD8 cells, but not IL-17 responses.

Assessing Historical and Current Threats to Common Frog (Rana Temporaria) Populations in Ireland

Ponds are an ephemeral feature of the landscape but their large-scale loss can have profound implications for biodiversity and the persistence of amphibian populations. We quantified rates of pond loss throughout Ireland over a period of approximately 125 yr. Environmental parameters and perceived risk factors associated with the current occurrence and density of the Common Frog, Rana temporaria, were also analyzed. The numbers of farmland ponds declined by 54% between 1887–1913 and 2005–11, with most ponds and the greatest losses
in the East, coincident with agricultural intensification and human habitation. The decline of pond numbers was significant but, at approximately 0.5% per annum, was substantially less than losses recorded in other European countries. Losses were coincident with major changes to the agricultural landscape including extensive land drainage. However, losses of pond and natural wetland habitats throughout Ireland may have been partially or wholly mitigated by a synchronous expansion of artificial field margin ditches associated with drainage projects during the mid-20th Century. The ecology of the Common Frog in Ireland was similar to its ecology elsewhere and it appears largely unaffected by pollution and disturbance. Consequently, the conservation status of the frog in Ireland was judged ‘‘favorable’’ and should remain so for the foreseeable future.

On the Complexity of Universal Leader Election

Electing a leader is a fundamental task in distributed computing. In its implicit version, only the leader must know who is the elected leader. This paper focuses on studying the message and time complexity of randomized implicit leader election in synchronous distributed networks. Surprisingly, the most "obvious" complexity bounds have not been proven for randomized algorithms. The "obvious" lower bounds of O(m) messages (m is the number of edges in the network) and O(D) time (D is the network diameter) are non-trivial to show for randomized (Monte Carlo) algorithms. (Recent results that show that even O(n) (n is the number of nodes in the network) is not a lower bound on the messages in complete networks, make the above bounds somewhat less obvious). To the best of our knowledge, these basic lower bounds have not been established even for deterministic algorithms (except for the limited case of comparison algorithms, where it was also required that some nodes may not wake up spontaneously, and that D and n were not known).

We establish these fundamental lower bounds in this paper for the general case, even for randomized Monte Carlo algorithms. Our lower bounds are universal in the sense that they hold for all universal algorithms (such algorithms should work for all graphs), apply to every D, m, and n, and hold even if D, m, and n are known, all the nodes wake up simultaneously, and the algorithms can make anyuse of node's identities. To show that these bounds are tight, we present an O(m) messages algorithm. An O(D) time algorithm is known. A slight adaptation of our lower bound technique gives rise to an O(m) message lower bound for randomized broadcast algorithms.

An interesting fundamental problem is whether both upper bounds (messages and time) can be reached simultaneously in the randomized setting for all graphs. (The answer is known to be negative in the deterministic setting). We answer this problem partially by presenting a randomized algorithm that matches both complexities in some cases. This already separates (for some cases) randomized algorithms from deterministic ones. As first steps towards the general case, we present several universal leader election algorithms with bounds that trade-off messages versus time. We view our results as a step towards understanding the complexity of universal leader election in distributed networks.

Active use of DFIG based Wind Farms for Transient Stability Improvement during Grid Disturbances

The doubly-fed induction generator (DFIG) now represents the dominant technology in wind turbine design. One consequence of this is limited damping and inertial response during transient grid disturbances. A dasiadecoupledpsila strategy is therefore proposed to operate the DFIG grid-side converter (GSC) as a static synchronous compensator (STATCOM) during a fault, supporting the local voltage, while the DFIG operates as a fixed-speed induction generator (FSIG) providing an inertial response. The modeling aspects of the decoupled control strategy, the selection of protection control settings, the significance of the fault location and operation at sub- and super-synchronous speeds are analyzed in detail. In addition, a case study is developed to validate the proposed strategy under different wind penetrations levels. The simulations show that suitable configuration of the decoupled strategy can be deployed to improve system voltage stability and inertial response for a range of scenarios, especially at high wind penetration. The conclusions are placed in context of the practical limitations of the technology employed and the system conditions.

Measurement-based Method for Wind Farm Power System Oscillation Monitoring

The global increase in the penetration of renewable energy is pushing electrical power systems into uncharted territory, especially in terms of transient and dynamic stability. In particular, the greater penetration of wind generation in European power networks is, at times, displacing a significant capacity of conventional synchronous generation with fixed-speed induction generation and now more commonly, doubly-fed induction generators. The impact of such changes in the generation mix requires careful monitoring to assess the impact on transient and dynamic stability. This paper presents a measurement based method for the early detection of power system oscillations, with attention to mode damping, in order to raise alarms and develop strategies to actively improve power system dynamic stability and security. A method is developed based on wavelet transform and support vector data description (SVDD) to detect oscillation modes in wind farm output power, which may excite dynamic instabilities in the wider system. The wavelet transform is used as a filter to identify oscillations in different frequency bands, while SVDD is used to extract dominant features from different scales and generate an assessment boundary according to the extracted features. Poorly damped oscillations of a large magnitude or that are resonant can be alarmed to the system operator, to reduce the risk of system instability. Method evaluation is exemplified used real data from a chosen wind farm.

Patterns of synchrony in natterjack toad breeding activity and reproductive success at local and regional scales

Empirical studies of the spatiotemporal dynamics of populations are required to better understand natural fluctuations in abundance and reproductive success, and to better target conservation and monitoring programmes. In particular, spatial synchrony in amphibian populations remains little studied. We used data from a comprehensive three year study of natterjack toad Bufo calamita populations breeding at 36 ponds to assess whether there was spatial synchrony in the toad breeding activity (start and length of breeding season, total number of egg strings) and reproductive success (premetamorphic survival and production of metamorphs). We defined a novel approach to assess the importance of short-term synchrony at both local and regional scales. The approach employs similarity indices and quantifies the interaction between the temporal and spatial components of populations using mixed effects models. There was no synchrony in the toad breeding activity and reproductive success at the local scale, suggesting that populations function as individual clusters independent of each other. Regional synchrony was apparent in the commencement and duration of the breeding season and in the number of egg strings laid (indicative of female population size). Regional synchrony in both rainfall and temperature are likely to explain the patterns observed (e.g. Moran effect). There was no evidence supporting regional synchrony in reproductive success, most likely due to spatial variability in the environmental conditions at the breeding ponds, and to differences in local population fitness (e.g. fecundity). The small scale asynchronous dynamics and regional synchronous dynamics in the number of breeding females indicate that it is best to monitor several populations within a subset of regions. Importantly, variations in the toad breeding activity and reproductive success are not synchronous, and it is thus important to consider them both when assessing the conservation status of pond-breeding amphibians. © 2012 The Authors. Ecography © 2012 Nordic Society Oikos.

Sublinear Bounds for Randomized Leader Election

This paper concerns randomized leader election in synchronous distributed networks. A distributed leader election algorithm is presented for complete n-node networks that runs in O(1) rounds and (with high probability) takes only O(n-vlog3/2n) messages to elect a unique leader (with high probability). This algorithm is then extended to solve leader election on any connected non-bipartiten-node graph G in O(t(G)) time and O(t(G)n-vlog3/2n) messages, where t(G) is the mixing time of a random walk on G. The above result implies highly efficient (sublinear running time and messages) leader election algorithms for networks with small mixing times, such as expanders and hypercubes. In contrast, previous leader election algorithms had at least linear message complexity even in complete graphs. Moreover, super-linear message lower bounds are known for time-efficientdeterministic leader election algorithms. Finally, an almost-tight lower bound is presented for randomized leader election, showing that O(n-v) messages are needed for any O(1) time leader election algorithm which succeeds with high probability. It is also shown that O(n 1/3) messages are needed by any leader election algorithm that succeeds with high probability, regardless of the number of the rounds. We view our results as a step towards understanding the randomized complexity of leader election in distributed networks.

Load Balanced Scalable Byzantine Agreement through Quorum Building, with Full Information

We address the problem of designing distributed algorithms for large scale networks that are robust to Byzantine faults. We consider a message passing, full information model: the adversary is malicious, controls a constant fraction of processors, and can view all messages in a round before sending out its own messages for that round. Furthermore, each bad processor may send an unlimited number of messages. The only constraint on the adversary is that it must choose its corrupt processors at the start, without knowledge of the processors’ private random bits.

A good quorum is a set of O(logn) processors, which contains a majority of good processors. In this paper, we give a synchronous algorithm which uses polylogarithmic time and Õ(vn) bits of communication per processor to bring all processors to agreement on a collection of n good quorums, solving Byzantine agreement as well. The collection is balanced in that no processor is in more than O(logn) quorums. This yields the first solution to Byzantine agreement which is both scalable and load-balanced in the full information model.

The technique which involves going from situation where slightly more than 1/2 fraction of processors are good and and agree on a short string with a constant fraction of random bits to a situation where all good processors agree on n good quorums can be done in a fully asynchronous model as well, providing an approach for extending the Byzantine agreement result to this model.

Sublinear bounds for randomized leader election

This paper concerns randomized leader election in synchronous distributed networks. A distributed leader election algorithm is presented for complete n-node networks that runs in O(1) rounds and (with high probability) uses only O(√ √nlog^3/2n) messages to elect a unique leader (with high probability). When considering the "explicit" variant of leader election where eventually every node knows the identity of the leader, our algorithm yields the asymptotically optimal bounds of O(1) rounds and O(. n) messages. This algorithm is then extended to one solving leader election on any connected non-bipartite n-node graph G in O(τ(. G)) time and O(τ(G)n√log^3/2n) messages, where τ(. G) is the mixing time of a random walk on G. The above result implies highly efficient (sublinear running time and messages) leader election algorithms for networks with small mixing times, such as expanders and hypercubes. In contrast, previous leader election algorithms had at least linear message complexity even in complete graphs. Moreover, super-linear message lower bounds are known for time-efficient deterministic leader election algorithms. Finally, we present an almost matching lower bound for randomized leader election, showing that Ω(n) messages are needed for any leader election algorithm that succeeds with probability at least 1/. e+. ε, for any small constant ε. >. 0. We view our results as a step towards understanding the randomized complexity of leader election in distributed networks.

Variance-Constrained Capacity of the Molecular Timing Channel with Synchronization Error

Molecular communication is set to play an important role in the design of complex biological and chemical systems. An important class of molecular communication systems is based on the timing channel, where information is encoded in the delay of the transmitted molecule - a synchronous approach. At present, a widely used modeling assumption is the perfect synchronization between the transmitter and the receiver. Unfortunately, this assumption is unlikely to hold in most practical molecular systems. To remedy this, we introduce a clock into the model - leading to the molecular timing channel with synchronization error. To quantify the behavior of this new system, we derive upper and lower bounds on the variance-constrained capacity, which we view as the step between the mean-delay and the peak-delay constrained capacity. By numerically evaluating our bounds, we obtain a key practical insight: the drift velocity of the clock links does not need to be significantly larger than the drift velocity of the information link, in order to achieve the variance-constrained capacity with perfect synchronization.

Neolithic settlement at the woodland’s edge: palynological data and timber architecture in Orkney, Scotland

It has often been assumed that the islands of Orkney were essentially treeless throughout much of the Holocene, with any ‘scrub’ woodland having been destroyed by Neolithic farming communities by around 3500 cal. BC. This apparently open, hyper-oceanic environment would presumably have provided quite marginal conditions for human settlement, yet Neolithic communities flourished and the islands contain some of the most spectacular remains of this period in north-west Europe. The study of new Orcadian pollen sequences, in conjunction with the synthesis of existing data, indicates that the timing of woodland decline was not synchronous across the archipelago, beginning in the Mesolithic, and that in some areas woodland persisted into the Bronze Age. There is also evidence to suggest that woodland communities in Orkney were more diverse, and therefore that a wider range of resources was available to Neolithic people, than has previously been assumed. Recent archaeological investigations have revealed evidence for timber buildings at early Neolithic settlement sites, suggesting that the predominance of stone architecture in Neolithic Orkney may not have been due to a lack of timber as has been supposed. Rather than simply reflecting adaptation to resource constraints, the reasons behind the shift from timber to stone construction are more complex and encompass social, cultural and environmental factors.

Transatlantic distribution of the Alaskan White River Ash

Volcanic ash layers preserved within the geologic record represent precise time markers that correlate disparate depositional environments and enable the investigation of synchronous and/or asynchronous behaviors in Earth system and archaeological sciences. However, it is generally assumed that only exceptionally powerful events, such as supereruptions (≥450 km3 of ejecta as dense-rock equivalent; recurrence interval of ∼105 yr), distribute ash broadly enough to have an impact on human society, or allow us to address geologic, climatic, and cultural questions on an intercontinental scale. Here we use geochemical, age, and morphological evidence to show that the Alaskan White River Ash (eastern lobe; A.D. 833–850) correlates to the “AD860B” ash (A.D. 846–848) found in Greenland and northern Europe. These occurrences represent the distribution of an ash over 7000 km, linking marine, terrestrial, and ice-core records. Our results indicate that tephra from more moderate-size eruptions, with recurrence intervals of ∼100 yr, can have substantially greater distributions than previously thought, with direct implications for volcanic dispersal studies, correlation of widely distributed proxy records, and volcanic hazard assessment.

The latest LGM culmination of the Garda Glacier (Italian Alps) and the onset of glacial termination. Age of glacial collapse and vegetation chronosequence

In the deglacial sequence of the largest end moraine system of the Italian Alps, we focused on the latest culmination of the Last Glacial Maximum, before a sudden downwasting of the piedmontane lobe occupying the modern lake basin. We obtained a robust chronology for this culmination and for the subsequent deglacial history by cross-radiocarbon dating of a proximal fluvioglacial plain and of a deglacial continuous lake sedimentation. We used reworked dinocysts to locate sources of glacial abrasion and to mark the input of glacial meltwater until depletion. The palynological record from postglacial lake sediments provided the first vegetation chronosequence directly reacting to the early Lateglacial withdrawal so far documented in the Alps.

Glacier collapse occurred soon after 17.46 +/- 0.2 ka cal BP, which is, the Manerba advance culmination. Basin deglaciation of several overdeepened foreland piedmont lakes on southern and northern sides of the Alps appears to be synchronous at millennial scale and near-synchronous with large-scale glacial retreat at global scale. The pioneering succession shows a first afforestation step at a median modeled age of 64 years after deglaciation, while rapid tree growth lagged 7 centuries. Between 16.4 +/- 0.16 and 15.5 +/- 0.16 ka cal BP, a regressive phase interrupted forest growth marking a Lateglacial phase of continental-dry climate predating GI-1. This event, spanning the most advanced phases of North-Atlantic H1, is consistently radiocarbon-framed at three deglacial lake records so far investigated on the Italian side of the Alps. Relationships with the Gschnitz stadial from the Alpine record of Lateglacial advances are discussed

Small Signal Stability Performance of Power System during High Penetration of Wind Generation

The small signal stability of interconnected power systems is one of the important aspects that need to be investigated since the oscillations caused by this kind of instability have caused many incidents. With the increasing penetration of wind power in the power system, particularly doubly fed induction generator (DFIG), the impact on the power system small signal stability performance should be fully investigated. Because the DFIG wind turbine integration is through a fast action converter and associated control, it does not inherently participate in the electromechanical small signal oscillation. However, it influences the small signal stability by impacting active power flow paths in the network and replacing synchronous generators that have power system stabilizer (PSS). In this paper, the IEEE 39 bus test system has been used in the analysis. Furthermore, four study cases and several operation scenarios have been conducted and analysed. The selective eigenvalue Arnoldi/lanczos's method is used to obtain the system eigenvalue in the range of frequency from 0.2 Hz to 2 Hz which is related to electromechanical oscillations. Results show that the integration of DFIG wind turbines in a system during several study cases and operation scenarios give different influence on small signal stability performance.

Biological control of the fish louse in a rainbow trout fishery

Novel egg-laying boards were found to be effective in the biological control of the freshwater fish louse Argulus foliaceus in a 12.9 ha rainbow trout Oncorhynchus mykiss fishery which had a high prevalence and intensity of infection of juvenile parasites in the early spring of 1999. Approximately 228 000d during an extensive 14 week period of egg laying which peaked in June 1999. In contrast, only 1566 clutches were harvested in 2000, when egg laying activity showed a bi-modal distribution, peaking in May and again in July and August. iaceus on rainbow trout in consecutive years was 2.9 : 1 and 2.1 : 1. Estimates of the size of the female A. foliaceus population based on egg-laying activity in 1999 exceeded that derived from measurements of prevalence and intensity of infection, whereas in 2000, this was more in balance. A minimum temperature of 10 degree C was identified for egg laying, which occurred continuously from May to October in a broadly synchronous manner.. Copyright 2002 The Fisheries Society of the British Isles