MicroRNA-132 is a physiological regulator of hematopoietic stem cell function and B-cell development

MicroRNAs are a class of small non-coding RNAs that negatively regulate gene expression. Several microRNAs have been implicated in altering hematopoietic cell fate decisions. Importantly, deregulation of many microRNAs can lead to deleterious consequences in the hematopoietic system, including the onset of cancer, autoimmunity, or a failure to respond effectively to infection. As such, microRNAs fine-tune the balance between normal hematopoietic output and pathologic consequences. In this work, we explore the role of two microRNAs, miR-132 and miR-125b, in regulating hematopoietic stem cell (HSC) function and B cell development. In particular, we uncover the role of miR-132 in maintaining the appropriate balance between self-renewal, differentiation, and survival in aging HSCs by buffering the expression of a critical transcription factor, FOXO3. By maintain this balance, miR-132 may play a critical role in preventing aging-associated hematopoietic conditions such as autoimmune disease and cancer. We also find that miR-132 plays a critical role in B cell development by targeting a key transcription factor, Sox4, that is responsible for the differentiation of pro-B cells into pre-B cells. We find that miR-132 regulates B cell apoptosis, and by delivering miR-132 to mice that are predisposed to developing B cell cancers, we can inhibit the formation of these cancers and improve the survival of these mice. In addition to miR-132, we uncovered the role of another critical microRNA, miR-125b, that potentiates hematopoietic stem cell function. We found that enforced expression of miR-125b causes an aggressive myeloid leukemia by downregulation of its target Lin28a. Importantly, miR-125b also plays a critical role in inhibiting the formation of pro-B cells. Thus, we have discovered two microRNAs with important roles in regulating normal hematopoiesis, and whose dregulation can lead to deleterious consequences such as cancer in the aging hematopoietic system. Both miR-132 and miR-125b may therefore be targeted for therapeutics to inhibit age-related immune diseases associated with the loss of HSC function and cancer progression.

Episodic variations in stream water chemistry associated with acid rainfall and run-off and the effect on aquatic ecosystem, with particular reference to fish populations in N.W. England

This is the episodic variations in stream water chemistry associated with acid rainfall and run-off and the effect on aquatic ecosystems, with particular reference to fish populations in North West England produced by the North West Water Authority in 1985. This report looks at the biological, physical and chemical information collected over a five year period from over 100 sites on upland streams in the North West Region of which drained rocks of low buffering capacity. In both Lake District and South Pennine sites striking differences were found between the composition of invertebrate communities inhabiting acid-stressed and less acid-stressed streams. Electric fishing surveys showed that acidic streams (geometric mean pH <5.5) generally had abnormally low densities of salmonids ( < 0 .2m2) and that 0+ fish were very few or absent. The latter indicates recruitment failure. Salmon were more sensitive than trout to low pH.

Male-infant-male interactions in Tibetan macaques

Event-sampling and scans were used for collecting data on male-infant-male triadic interactions, and their effects on member spacing respectively in a group of Macaca thibetana at Mt. Emei in 1989. The group was partially provisioned by human visitors in seasons other than winter, and could be observed closely. In addition, a stable linear male-hierarchy among five males existed for two years since the end of 1987, providing a good social condition for this topic. The triadic interactions were specific to the birth season, and recognized as three types being on a continuum functionally changing from passive ''agonistic buffering'' (4.8%) to active spatial cohesion, which resulted in a significant decline of intermale distances. Positive correlations were documented between the triad initiation rate and the number of females in consort with the males in the mating season (MS), and between the triad reception rate and the number of infants in proximity to the males in the MS when maternal care was significantly reduced. Thus the male's mating effort and kin/sexual selection may deeply be involved in the triad of this species. Considering that the two triad-species, M. sylvanus and M. thibetana, had different levels of paternity, but shared similar foraging conditions, and showed similar intensities of male-infant caretaking, the triad was very likely a byproduct of male-infant caretaking, which was probably shaped to compensate heavy maternal investment to young offspring in harsh conditions. Accordingly, the long-term arguments about the triad in M. sylvanus can be united to a model of the way in which ''male-infant caretaking'' hypothesis works ultimately, and ''regulating social relations'' hypothesis does proximately.

The night purging of a two-storey atrium building

We examine the fluid mechanics of night purging in a two-storey naturally ventilated atrium building. We develop a mathematical model of a simplified atrium building and focus on the rate at which warm air purges from each storey and the atrium by displacement ventilation into a still cool night environment of a constant temperature. To develop a first insight into how the geometry of the building influences the rate at which warm air purges from each storey via the atrium we neglect heat exchange with the fabric (so there is no thermal buffering) and furthermore assume that the warm air layers in each storey and the atrium are of uniform temperature. The plumes of warm air that rise from the storeys into the atrium, causing the atrium to fill with warm air, have a very strong influence on the night purge. Modelling these as axisymmetric turbulent plumes, we identify three forms of purging behaviour. Each purge is characterised by five key times identified in the progression of the night purge and physical rationale for these differing behaviours is given. An interface velocity deficit and volumetric purge deficit are introduced as measures of the efficiency of a night purge. © 2010 Elsevier Ltd.

A low latency optical top of rack switch for data centre networks with minimized processor energy load

We propose a low latency optical data center top of rack switch using recirculation buffering and a hybrid MZ/SOA switch architecture to reduce the network power dissipated on future optically connected server chips by 53%. © OSA 2014.

高速缓存优化的并行连接算法

由于嵌套循环连接操作过程中存在较大的高速缓存缺失,严重影响了连接查询的性能。提出了一种基于缓冲的高速缓存参数无关的嵌套循环并行连接算法。通过高速缓存参数无关和缓冲技术,提高了连接算法的空间局部性和时间局部性。理论分析和实验结果表明,高速缓存优化后的串行连接算法的性能是原来的2倍,其并行算法效果近似线性加速比。

Transfer and transport of phosphorus and silica in the turbidity maximum zone of the Changjiang estuary

The concentration of suspended particulate matter (SPM), sedimentation flux, and various forms of phosphorus and silica in turbidity maximum zone (TMZ) in the Changjiang (Yangtze) estuary was studied. Based on the budget of P and Si, their mass balances in the TMZ were calculated. Results show that the variation in concentration of dissolved inorganic silicon (DISi) was mainly controlled by seawater dilution, while that of dissolved inorganic phosphor-us (DIP) was considerably affected by the buffering of suspended matter and sediment. Our experiments showed that the sedimentation fluxes of SPM and particulate inorganic phosphorus (PIP), total particulate phosphorus (TPP), particulate inorganic silicon (PISi), and biological silicon (BSi) in the TMZ were 238.4 g m(-2) d(-1) and 28.3, 43.1, 79.0, 63.0 mg m(-2) d(-1), respectively. In addition, a simple method to estimate the ratio of resuspension of sediment in the TMZ was established, with which the rate in surface and bottom waters of the TMZ accounted for 55.7 and 66.1% of the total SPM, respectively, indicating that the sediment resuspension in the TMZ influenced significantly the mass balances of P and Si. Particulate adsorbed P (60.8%) and 35.5% of total particulate P discharged from the river were filtered and then deposited in the TMZ. The input flux of PIP from the river mouth was 55.9% of that of DIP, being important as biologically available P, while that of PISi was only 3.5% of DISi, showing that particulate adsorbed Si was much less important than particulate adsorbed P. (c) 2008 Elsevier Ltd. All rights reserved.

滚石机理及滚石灾害评价研究

Rockfall is a geological evolution process involving detachment of blocks or boulders from a slope face, then their free falls, bouncing, rolling or sliding, and finally deposition near the toe of the slope. Many facts indicate that the rockfall can cause hazards to peoples, and it can be regarded as a geological hazard. A rockfall event may only involve a boulder or rock, and also several ones. When there are peoples, buildings, or other man-made establishments within the scope of rockfall trajectory, losses will be possibly induced in tenns of human lives or damages to these facilities. Researches into mechanism, kinematics, dynamics, hazard assessment, risk analysis, and mitigation measures of rockfalls are extremely necessary and important. Occurrence of rockfall is controlled by a lot of conditions, mainly including topographical, geomorphic, geological ones and triggering factors. The rockfall especially in mountainous areas, has different origins, and occurs to be frequent, unexpected, uncertain, in groups, periodic and sectional. The characterization and classification of the rockfalls not only increase knowledge about rockfall mechanism, but also can instruct mitigation of the hazards. In addition, stability of potential rockfalls have various sensitivity to different triggering factors and changes of geometrical conditions. Through theoretical analyses, laboratory experiments and field tests, the author presents some back-analysis methods for friction coefficients of sliding and rolling, and restitution coefficients. The used input data can be obtained economically and accurately in the field. Through deep studies on hazard assessment methods and analysis of factors influencing rockfall hazard, this paper presents a new assessment methodology consisting of preliminary assessment and detailed one. From the application in a 430 km long stretch of the Highway, which is located between Paksho and Nyingtri in Tibet, the methodology can be applicable for the rockfall hazard assessment in complex and difficult terrains. In addition, risk analyses along the stretch are conducted by computing the probability of encountering rockfalls and life losses resulting from rockfall impacts. Rockfall hazards may be mitigated by avoiding hazardous areas, clearness of dangerous rocks, reinforcement, obstructing the rockfalls, leading the rockfalls, warning and monitoring for rockfalls, etc. Seen from present remedial level of rockfall hazards, different mitigation measures, economical and effective buffering units, monitoring tecliniques and consciousness of environmental protection for rockfall mitigations should be further developed.

Reliable Interconnection Networks for Parallel Computers

This technical report describes a new protocol, the Unique Token Protocol, for reliable message communication. This protocol eliminates the need for end-to-end acknowledgments and minimizes the communication effort when no dynamic errors occur. Various properties of end-to-end protocols are presented. The unique token protocol solves the associated problems. It eliminates source buffering by maintaining in the network at least two copies of a message. A token is used to decide if a message was delivered to the destination exactly once. This technical report also presents a possible implementation of the protocol in a worm-hole routed, 3-D mesh network.

Using Warp to Control Network Contention in Mermera

Parallel computing on a network of workstations can saturate the communication network, leading to excessive message delays and consequently poor application performance. We examine empirically the consequences of integrating a flow control protocol, called Warp control [Par93], into Mermera, a software shared memory system that supports parallel computing on distributed systems [HS93]. For an asynchronous iterative program that solves a system of linear equations, our measurements show that Warp succeeds in stabilizing the network's behavior even under high levels of contention. As a result, the application achieves a higher effective communication throughput, and a reduced completion time. In some cases, however, Warp control does not achieve the performance attainable by fixed size buffering when using a statically optimal buffer size. Our use of Warp to regulate the allocation of network bandwidth emphasizes the possibility for integrating it with the allocation of other resources, such as CPU cycles and disk bandwidth, so as to optimize overall system throughput, and enable fully-shared execution of parallel programs.

dPAM: A Distributed Prefetching Protocol for Scalable Asynchronous Multicast in P2P Systems

We leverage the buffering capabilities of end-systems to achieve scalable, asynchronous delivery of streams in a peer-to-peer environment. Unlike existing cache-and-relay schemes, we propose a distributed prefetching protocol where peers prefetch and store portions of the streaming media ahead of their playout time, thus not only turning themselves to possible sources for other peers but their prefetched data can allow them to overcome the departure of their source-peer. This stands in sharp contrast to existing cache-and-relay schemes where the departure of the source-peer forces its peer children to go the original server, thus disrupting their service and increasing server and network load. Through mathematical analysis and simulations, we show the effectiveness of maintaining such asynchronous multicasts from several source-peers to other children peers, and the efficacy of prefetching in the face of peer departures. We confirm the scalability of our dPAM protocol as it is shown to significantly reduce server load.

GreedyDual-Join: Locality-Aware Buffer Management for Approximate Join Processing Over Data Streams

We investigate adaptive buffer management techniques for approximate evaluation of sliding window joins over multiple data streams. In many applications, data stream processing systems have limited memory or have to deal with very high speed data streams. In both cases, computing the exact results of joins between these streams may not be feasible, mainly because the buffers used to compute the joins contain much smaller number of tuples than the tuples contained in the sliding windows. Therefore, a stream buffer management policy is needed in that case. We show that the buffer replacement policy is an important determinant of the quality of the produced results. To that end, we propose GreedyDual-Join (GDJ) an adaptive and locality-aware buffering technique for managing these buffers. GDJ exploits the temporal correlations (at both long and short time scales), which we found to be prevalent in many real data streams. We note that our algorithm is readily applicable to multiple data streams and multiple joins and requires almost no additional system resources. We report results of an experimental study using both synthetic and real-world data sets. Our results demonstrate the superiority and flexibility of our approach when contrasted to other recently proposed techniques.

Fundamental studies of sourdoughs fermented with Weissella cibaria and Lactobacillus plantarum: influence on baking characteristics, sensory profiles and in vitro starch digestibility of gluten-free breads

The application of sourdough can improve texture, structure, nutritional value, staling rate and shelf life of wheat and gluten-free breads. These quality improvements are associated with the formation of organic acids, exopolysaccharides (EPS), aroma or antifungal compounds. Initially, the suitability of two lactic acid bacteria strains to serve as sourdough starters for buckwheat, oat, quinoa, sorghum and flours was investigated. Wheat flour was chosen as a reference. The obligate heterofermentative lactic acid bacterium (LAB) Weissella cibaria MG1 (Wc) formed the EPS dextran (a α-1,6-glucan) from sucrose in situ with a molecular size of 106 to 107 kDa. EPS formation in all breads was analysed using size exclusion chromatography and highest amounts were formed in buckwheat (4 g/ kg) and quinoa sourdough (3 g/ kg). The facultative heterofermentative Lactobacillus plantarum FST1.7 (Lp) was identified as strong acidifier and was chosen due to its ubiquitous presence in gluten-free as well as wheat sourdoughs (Vogelmann et al. 2009). Both Wc and Lp, showed highest total titratable acids in buckwheat (16.8 ml; 26.0 ml), teff (16.2 ml; 24.5 ml) and quinoa sourdoughs (26.4 ml; 35.3 ml) correlating with higher amounts of fermentable sugars and higher buffering capacities. Sourdough incorporation reduced the crumb hardness after five days of storage in buckwheat (Wc -111%), teff (Wc -39%) and wheat (Wc -206%; Lp -118%) sourdough breads. The rate of staling (N/ day) was reduced in buckwheat (Ctrl 8 N; Wc 3 N; Lp 6 N), teff (Ctrl 13 N; Wc 9 N; Lp 10 N) and wheat (Ctrl 5 N; Wc 1 N; Lp 2 N) sourdough breads. Bread dough softening upon Wc and Lp sourdough incorporation accounted for increased crumb porosity in buckwheat (+10.4%; +4.7), teff (+8.1%; +8.3%) and wheat sourdough breads (+8.7%; +6.4%). Weissella cibaria MG1 sourdough improved the aroma quality of wheat bread but had no impact on aroma of gluten-free breads. Microbial shelf life however, was not prolonged in any of the breads regardless of the starter culture used. Due to the high prevalence of insulin-dependent diabetes mellitus particular amongst coeliac patients, glycaemic control is of great (Berti et al. 2004). The in vitro starch digestibility of gluten-free breads with and without sourdough addition was analysed to predict the GI (pGI). Sourdough can decrease starch hydrolysis in vitro, due to formation of resistant starch and organic acids. Predicted GI of gluten-free control breads were significantly lower than for the reference white wheat bread (GI=100). Starch granule size was investigated with scanning electron microscopy and was significantly smaller in quinoa flour (<2 μm). This resulted in higher enzymatic susceptibility and hence higher pGI for quinoa bread (95). Lowest hydrolysis indexes for sorghum and teff control breads (72 and 74, respectively) correlate with higher gelatinisation peak temperatures (69°C and 71°C, respectively). Levels of resistant starch were not increased by addition of Weissella cibaria MG1 (weak acidifier) or Lactobacillus plantarum FST1.7 (strong acidifier). The pGI was significantly decreased for both wheat sourdough breads (Wc 85; Lp 76). Lactic acid can promote starch interactions with gluten hence decreasing starch susceptibility (Östman et al. 2002). For most gluten-free breads, the pGI was increased upon sourdough addition. Only sorghum and teff Lp sourdough breads (69 and 68, respectively) had significantly decreased pGI. Results suggest that the increase of starch hydrolysis in gluten-free breads was related to mechanism other than presence of organic acids and formation of resistant starch.

Health in the medieval world: Regionality and the bioarchaeology of Ireland and Britain

This study assesses regional health patterns in early medieval Ireland and Britain by analysing and interpreting palaeopathological indicators of stress. This was achieved by incorporating the results of demographic and palaeopathological study into the specific historical contexts. Although relatively small islands, both are home to unique and diverse cultural, physical, and political landscapes, which could potentially affect the general health of the population in different ways. To accurately answer the research question, a bioarchaeological survey of six regions within both islands was carried out, specifically analysing and comparing the demographic profile and general health trends within each region with one another. Results from the analysis have demonstrated statistically significant differences within and between the islands. Inferring that even the more subtle differences observed within the cultural, physical, and political landscapes, such as in the case of Ireland and Britain, can and do affect general health trends. The health of early medieval Ireland and Britain appears to be significantly affected by the physical landscape, specifically a north/south divide. The most northerly regions, Scotland South and Ireland North, manifested higher levels of stress indicators when compared to the more southerly positioned regions. Although it can only be hypothesised what factors within these regions are causing, enhancing or buffering stress, the study has established the potential and necessity for regional work to be continued when interpreting the historical past of these two islands.

Potential impacts of leakage from deep CO2 geosequestration on overlying freshwater aquifers.

Carbon Capture and Storage may use deep saline aquifers for CO(2) sequestration, but small CO(2) leakage could pose a risk to overlying fresh groundwater. We performed laboratory incubations of CO(2) infiltration under oxidizing conditions for >300 days on samples from four freshwater aquifers to 1) understand how CO(2) leakage affects freshwater quality; 2) develop selection criteria for deep sequestration sites based on inorganic metal contamination caused by CO(2) leaks to shallow aquifers; and 3) identify geochemical signatures for early detection criteria. After exposure to CO(2), water pH declines of 1-2 units were apparent in all aquifer samples. CO(2) caused concentrations of the alkali and alkaline earths and manganese, cobalt, nickel, and iron to increase by more than 2 orders of magnitude. Potentially dangerous uranium and barium increased throughout the entire experiment in some samples. Solid-phase metal mobility, carbonate buffering capacity, and redox state in the shallow overlying aquifers influence the impact of CO(2) leakage and should be considered when selecting deep geosequestration sites. Manganese, iron, calcium, and pH could be used as geochemical markers of a CO(2) leak, as their concentrations increase within 2 weeks of exposure to CO(2).