OBJECTIVES/GOALS: This study seeks to culture and characterize mucus-degrading microbes from the microbiome of inflammatory bowel disease (IBD) patients. METHODS/STUDY POPULATION: Stool will be collected from IBD patients and healthy first-degree relatives, then enriched for mucin-degrading microbes through growth on porcine rectal mucin. Dilution plating in both liquid and solid culture formats will be employed to isolate strains capable of growth on mucin. Cultures that are positive for mucin degradation will be identified with 16S rRNA sequencing; unique isolates will be genome sequenced and transcriptionally profiled on simple monosaccharides and mucin in order to identify putative mucin-degrading genes. The abundance of novel enzymes, pathways, and microbes will be compared in healthy and IBD patient populations using existing datasets in the literature. RESULTS/ANTICIPATED RESULTS: We expect to isolate previously uncultured mucin-degrading microbes, which will likely include new strains and possibly new species of bacteria. Through the transcriptomic characterization of mucin-degrading pathways, we will expand the lexicon of known mucin-degrading enzymes and pathways used by bacteria in the human colon. We expect mucin-degrading microbes to be more abundant and active in IBD patients compared to healthy controls. DISCUSSION/SIGNIFICANCE OF IMPACT: There is no cure for IBD and treatment relies heavily on suppressing a patient’s immune system. This research seeks to understand the contribution of the gut microbiota in the pathogenesis of IBD, which may lead to future therapeutic targets.

The Hkakabo Razi region located in northern Myanmar is an Important Bird Area and part of the Eastern Himalayan Biodiversity Hotspot. Within the framework of the World Heritage Convention to enlist the site under criterion (ix) and (x), we conducted a biodiversity assessment for passerine birds using DNA barcoding and other molecular markers. Of the 441 bird species recorded, we chose 16 target species for a comparative phylogeographic study. Genetic analysis was performed for a larger number of species and helped identifying misidentified species. We found phylogeographic structure in all but one of the 16 study species. In 13 species, populations from northern Myanmar were genetically distinctive and local mitochondrial lineages differed from those found in adjacent regions by 3.9–9.9% uncorrected genetic distances (cytochrome-b). Since the genetic distinctiveness of study populations will be corroborated by further differences in morphology and song as in other South-East Asian passerines, many of them will be candidates for taxonomic splits, or in case an older taxon name is not available, for the scientific description of new taxa. Considering the short time frame of our study we predict that a great part of undetected faunal diversity in the Hkakabo Razi region will be discovered.

Background: The interaction between mutations in two or more genes is increasingly recognised as an important contributor to the phenotypic variability in genetic disorders. Co-occurrence of variants in SQSTM1 and TIA1 is reported as a cause of myopathy in 3 prior cases, but limited clinical data were presented. We present detailed clinical features of a family with two siblings having a distal myopathy with rimmed vacuoles (DMRV), and genetic variants in SQSTM1 and TIA1. Methods: Clinicopathologic study of a family with DMRV to describe clinical features, laboratory and neurophysiology studies, neuroimaging, and genetic sequencing. Results: Two siblings with variants in SQSTM1 and TIA1 developed myopathy in their early 60’s, with early involvement of ankle dorsiflexors and finger extensors. A decade after onset, patients remain ambulatory and have not developed cardiac or respiratory complications. MRI of the legs showed selective involvement of adductor magnus, vastus lateralis, and in lower legs the anterior compartment and medial gastrocnemius. Muscle pathology demonstrated rimmed vacuoles, disrupted myofibrillar architecture, and mislocalised TDP43. Two unaffected family members had one genetic variant but not both. Conclusions: We describe a fourth family with co-occurrence of TIA1 and SQSTM1 genetic variants and describe their detailed phenotype. Future study should address the mechanism of the interaction between these two variants.

Background: When measuring young Duchenne Muscular Dystrophy (DMD) patients’ health-related quality of life (HRQoL), parent-proxy reports are heavily relied on. Therefore, it is imperative that the relationship between parent-proxy and child self-report HRQoL is understood. This study examined the level of agreement between children and their parent-proxy rating of the child’s HRQoL. Methods: We used FOR-DMD clinical trial baseline data. HRQoL, measured using the PedsQL inventory, was reported by 178 parent and child (ages 4 to 7 years) dyads. Intracorrelation coefficients (ICC) measured absolute agreement while paired t-tests determined differences in the average HRQoL ratings between groups. Results: The level of agreement between child and parent-proxy ratings of HRQoL was poor for the generic PedsQL scale (ICC: 0.29) and its subscales; and, similarly low for the neuromuscular disease module (ICC:0.16). On average, parents rated their child’s HRQoL as poorer than the children rated themselves in all scales except for psychosocial and school functioning. Conclusions: Child and parent-proxy HRQoL ratings are discordant in this study sample, as occurs in other chronic pediatric diseases. This should be taken into account when interpreting clinical and research HRQoL findings in this population. Future studies should examine reasons for parents’ perception of poorer HRQoL than that reported by their children.

The prediction of solar flares, eruptions, and high energy particle storms is of great societal importance. The data mining approach to forecasting has been shown to be very promising. Benchmark datasets are a key element in the further development of data-driven forecasting. With one or more benchmark data sets established, judicious use of both the data themselves and the selection of prediction algorithms is key to developing a high quality and robust method for the prediction of geo-effective solar activity. We review here briefly the process of generating benchmark datasets and developing prediction algorithms.

The purpose of this paper is to explore a resolution for the Faint Young Sun Paradox that has been mostly rejected by the community, namely the possibility of a somewhat more massive young Sun with a large mass loss rate sustained for two to three billion years. This would make the young Sun bright enough to keep both the terrestrial and Martian oceans from freezing, and thus resolve the paradox. It is found that a large and sustained mass loss is consistent with the well observed spin-down rate of Sun-like stars, and indeed may be required for it. It is concluded that a more massive young Sun must be considered a plausible hypothesis.

There is a need to design intensive cropping systems that can reap multiple benefits from annual forages including animal feed, soil fertility and weed control. Considering pea/oat (Pisum sativum cv. 40–10/Avena sativa cv. Legget) as a standard green manure, this study investigated the productivity, weed competitiveness, utilization and nitrogen (N) benefit from grazed and ungrazed green manures to spring wheat (Triticum aestivum cv. Waskada) and fall rye (Secale cereale cv. Hazlet). A set of 3-year experiments was carried out in Carman, Manitoba, Canada in 2009, and was repeated in 2010 and 2011. Green manures were grazed by 2–3 ewes and 2–5 lambs for 24 h (1111–1667 sheep days per ha). Averaged over experiments pea/oat mix, hairy vetch (Vicia villosa L.) and sweetclover (Melilotus officinalis cv. Norgold) above-ground dry matter (DM) production were 5036, 5032 and 4064 kg ha−1, respectively. Lentil (Lens culinaris cv. Indianhead), a mixture of seven species and soybean (Glycine max cv. Prudence) produced the least amount of DM over 3 years; 3589, 3551, 3174 kg ha−1, respectively. Pea/oat and hairy vetch were the most weed-competitive species and, averaged over 3 years, contained less than 15% weed DM. Utilization of green manures by grazing animals varied little among species across years and ranged from 28 to 86% for individual species and years. When combined across experiments grazing increased N availability to the wheat crop. The grazing effect was significant for wheat DM production, N uptake and grain N, but not significant for yield across experiments. Averaged over 3 years, wheat took up 107 kg N ha−1 from grazed plots versus 98 kg N ha−1 from ungrazed plots. A significant species×management interaction for total (wheat+fall rye) N uptake in 2009 indicated that increasing the proportion of legumes in the green manure increased N benefit from grazing. Fall rye productivity was not affected by grazing. We recommend pea/oat and hairy vetch as two green manure species to enhance the overall system performance to achieve high level of DM production, good weed competition, utilization by sheep and provision of N benefit to the following wheat and fall rye crops.

We investigated a mixed outbreak of Legionnaires' disease (LD) and Pontiac fever (PF) at a military base to identify the outbreak's environmental source as well as known legionellosis risk factors. Base workers with possible legionellosis were interviewed and, if consenting, underwent testing for legionellosis. A retrospective cohort study collected information on occupants of the buildings closest to the outbreak source. We identified 29 confirmed and probable LD and 38 PF cases. All cases were exposed to airborne pathogens from a cooling tower. Occupants of the building closest to the cooling tower were 6·9 [95% confidence interval (CI) 2·2–22·0] and 5·5 (95% CI 2·1–14·5) times more likely to develop LD and PF, respectively, than occupants of the next closest building. Thorough preventive measures and aggressive responses to outbreaks, including searching for PF cases in mixed legionellosis outbreaks, are essential for legionellosis control.

The motivation for our research was to study the correlation between the chirality of filaments and the handedness (S- or Z-shape) of sigmoids. It was assumed that sigmoids would mostly coincide with filaments and that the S-shaped sigmoids would correlate well with filaments of sinistral chirality, which we found that to be at best a very weak relation. Since we had a full solar cycle of filament metadata at hand it was easy to verify the supposedly known hemispheric preference of filament chirality. We discovered that the hemispheric chirality rule was confirmed for the epoch where a thorough manual study had been performed, but that at other phases of the solar cycle the rule seems to disappear and sometimes even reverse.

Williams syndrome is a neurodevelopmental genetic disorder caused by a hemizygous deletion on chromosome 7q11.23, resulting in atypical brain structure and function, including abnormal morphology of the corpus callosum. An influence of handedness on the size of the corpus callosum has been observed in studies of typical individuals, but handedness has not been taken into account in studies of callosal morphology in Williams syndrome. We hypothesized that callosal area is smaller and the size of the splenium and isthmus is reduced in individuals with Williams syndrome compared to healthy controls, and examined age, sex, and handedness effects on corpus callosal area. Structural magnetic resonance imaging scans were obtained on 25 individuals with Williams syndrome (18 right-handed, 7 left-handed) and 25 matched controls. We found that callosal thickness was significantly reduced in the splenium of Williams syndrome individuals compared to controls. We also found novel evidence that the callosal area was smaller in left-handed participants with Williams syndrome than their right-handed counterparts, with opposite findings observed in the control group. This novel finding may be associated with LIM-kinase hemizygosity, a characteristic of Williams syndrome. The findings may have significant clinical implications in future explorations of the Williams syndrome cognitive phenotype.

Agricultural production systems that reduce the use of in-crop herbicides could greatly reduce risks of environmental damage and the development of herbicide-resistant weeds. Few studies have investigated the long-term effects of in-crop herbicide omissions on weed seedbank community size and structure. A crop-rotation study was sampled 10 yr after a strictly annual rotation and an annual/perennial rotation were exposed to different in-crop herbicide omission treatments. In-crop herbicides were applied either in all annual crops (control), omitted from oats only, or omitted from both flax and oats. Seedbank densities were greatest when in-crop herbicides were omitted from flax and oats, and this treatment also reduced crop yield. Shannon-Wiener diversity differed among crops in the annual crop rotation and among herbicide omission treatments in the perennial rotation. Herbicide omissions changed the weed-community structure in flax and in wheat and canola crops in the annual rotation enough to warrant alternate control methods in some treatments. The magnitude of the effects on the seedbank parameters depended largely on the competitive ability of the crop in which herbicides were omitted. No yield response to omitting herbicides in oats indicated that standard weed management practices have reduced weed populations below yield-loss thresholds.

The period doubling renormalization operator was introduced by Feigenbaum and by Coullet and Tresser in the 1970s to study the asymptotic small-scale geometry of the attractor of one-dimensional systems that are at the transition from simple to chaotic dynamics. This geometry turns out not to depend on the choice of the map under rather mild smoothness conditions. The existence of a unique renormalization fixed point that is also hyperbolic among generic smooth-enough maps plays a crucial role in the corresponding renormalization theory. The uniqueness and hyperbolicity of the renormalization fixed point were first shown in the holomorphic context, by means that generalize to other renormalization operators. It was then proved that, in the space of C2+α unimodal maps, for α>0, the period doubling renormalization fixed point is hyperbolic as well. In this paper we study what happens when one approaches from below the minimal smoothness thresholds for the uniqueness and for the hyperbolicity of the period doubling renormalization generic fixed point. Indeed, our main result states that in the space of C2 unimodal maps the analytic fixed point is not hyperbolic and that the same remains true when adding enough smoothness to get a priori bounds. In this smoother class, called C2+∣⋅∣, the failure of hyperbolicity is tamer than in C2. Things get much worse with just a bit less smoothness than C2, as then even the uniqueness is lost and other asymptotic behavior becomes possible. We show that the period doubling renormalization operator acting on the space of C1+Lip unimodal maps has infinite topological entropy.

The prevalence of Cryptosporidium in calves younger than 10 weeks was estimated in a cross-sectional epidemiological study on 100 dairy (n=499) and 50 beef (n=333) farms in East Flanders (Belgium), using a previously evaluated immunofluorescence assay (Merifluor®). The calf prevalence was 37% (95% Probability Interval (PI): 7–70%) in dairy calves and 12% (95% PI: 1–30%) in beef calves. To elucidate the genetic diversity, the Cryptosporidium 18S ribosomal DNA and the 70 kDa heat shock protein gene were targeted. In the majority of the samples C. parvum was present, although C. bovis was also identified, all but one in calves older than 1 month. The porcine-specific C. suis was identified in 1 beef calf. Subtyping of C. parvum positive isolates by sequence analysis of the 60 kDa glycoprotein gene indicated the presence of 4 allele IIa subtypes, along with 1 subtype IIdA22G1. The subtype IIaA15G2R1 was most prevalent, next to subtype IIaA13G2R1 and IIaA16G2R1, and a new subtype IIaA14G2R1. The results of the present study indicate a high prevalence of Cryptosporidium infections in calves in Belgium and confirm that these calves should be considered as a potential zoonotic reservoir for human infections.

The skeletal anatomy of the Early Permian eureptile Thuringothyris mahlendorffae from the Bromacker Quarry, Germany, is redescribed on the basis of several new specimens. The taxon retains some plesiomorphic characters, such as an ectopterygoid and a tabular, but it also possesses low neural spines and nonswollen neural arches, a combination that is unique for early eureptiles. A phylogenetic analysis places Thuringothyris as the sister taxon of Captorhinidae, excluding any potential “protorothyridid” affinities. Implications of this study are that the swollen neural arches of captorhinids and araeosceloids might have evolved independently, that a downturned rostrum occurred only later in captorhinid evolution, and that the European Permian is important to the understanding of the origin of eureptiles.

This paper proves a theorem about bounding orbits of a time dependent dynamical system. The maps that are involved are examples in convex dynamics, by which we mean the dynamics of piecewise isometries where the pieces are convex. The theorem came to the attention of the authors in connection with the problem of digital halftoning. Digital halftoning is a family of printing technologies for getting full-color images from only a few different colors deposited at dots all of the same size. The simplest version consists in obtaining gray-scale images from only black and white dots. A corollary of the theorem is that for error diffusion, one of the methods of digital halftoning, averages of colors of the printed dots converge to averages of the colors taken from the same dots of the actual images. Digital printing is a special case of a much wider class of scheduling problems to which the theorem applies. Convex dynamics has roots in classical areas of mathematics such as symbolic dynamics, Diophantine approximation, and the theory of uniform distributions.

The first dedicated local electrode atom probes (LEAP [a trademark of Imago Scientific Instruments Corporation]) have been built and tested as commercial prototypes. Several key performance parameters have been markedly improved relative to conventional three-dimensional atom probe (3DAP) designs. The Imago LEAP can operate at a sustained data collection rate of 1 million atoms/minute. This is some 600 times faster than the next fastest atom probe and large images can be collected in less than 1 h that otherwise would take many days. The field of view of the Imago LEAP is about 40 times larger than conventional 3DAPs. This makes it possible to analyze regions that are about 100 nm diameter by 100 nm deep containing on the order of 50 to 100 million atoms with this instrument. Several example applications that illustrate the advantages of the LEAP for materials analysis are presented.

Strategies for pesticide use reduction have suffered from limited adoption. The impact of such strategies will be greater if they appeal to farmers with typical demographics and attitudes. A participatory, on-farm study was conducted to assess the potential of Pesticide Free ProductionTM (PFP) [Pesticide Free ProductionTM and PFPTM are registered trademarks of the University of Manitoba.] to be widely implemented on mainstream farms in Manitoba, Canada. PFP is a flexible, simple framework intended to appeal broadly to farmers who may not have adopted other pesticide use reduction initiatives. It may also provide a marketable food product label. This novel crop production system prohibits the use of in-crop pesticides and seed treatments during one crop year, as well as prior use of residual pesticides. Applications of nonresidual pesticides (such as glyphosate) are permitted prior to crop emergence. Synthetic fertilizer use is permitted at any time. The objectives of this study were: (1) to determine if the demographic and attitudinal characteristics of farms and farmers participating in a PFP pilot project varied depending on the level of PFP implementation; and (2) to compare the characteristics of farms and farmers participating in the pilot project with standards representing average farms and farmers in Manitoba. A total of 71 farmers, representing 120 fields and 11 crops, participated in the study. Fields and farmers were categorized into three groups, based on whether or not fields: (1) achieved PFP certification status and (2) were in transition to organic production. There were few demographic differences among groups. Demographic characteristics of participating farmers were typical for Manitoba, with the exception that participating farmers who were not in transition to organic production had higher levels of education than a random sample of Manitoba farmers. Attitudinal orientation (adherence to a conventional versus an alternative agricultural paradigm) of participants who were not in transition to organic production was similar to that of a random sample of Manitoba farmers. Fields and farms on which PFP was implemented were relatively large in the context of Manitoba averages. Participants indicated high satisfaction with certifiable PFP crops and high levels of interest in implementing future PFP. Pesticide free production demonstrates significant potential for broad adoption in this region.