We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.

One major limitation of microbial community marker gene sequencing is that it does not provide direct information on the functional composition of sampled communities. Here, we present PICRUSt2 (https://github.com/picrust/picrust2), which expands the capabilities of the original PICRUSt method1 to predict the functional potential of a community based on marker gene sequencing profiles. This updated method and implementation includes several improvements over the previous algorithm: an expanded database of gene families and reference genomes, a new approach now compatible with any OTU-picking or denoising algorithm, and novel phenotype predictions. Upon evaluation, PICRUSt2 was more accurate than PICRUSt1 and other current approaches overall. PICRUSt2 is also now more flexible and allows the addition of custom reference databases. We highlight these improvements and also important caveats regarding the use of predicted metagenomes, which are related to the inherent challenges of analyzing metagenome data in general.

This guideline for the investigation and initial treatment of atypical hemolytic uremic syndrome (HUS) is intended to offer an approach based on opinion, as evidence is lacking. It builds on the current ability to identify the etiology of specific diagnostic sub-groups of HUS. HUS in children is mostly due to infection, enterohemorrhagic Escherichia coli (EHEC), Shigella dysenteriae type 1 in some geographic regions, and invasive Streptococcus pneumoniae. These sub-groups are relatively straightforward to diagnose. Their management, which is outside the remit of this guideline, is related to control of infection where that is necessary and supportive measures for the anemia and acute renal failure. A thorough investigation of the remainder of childhood HUS cases, commonly referred to as "atypical" HUS, will reveal a risk factor for the syndrome in approximately 60% of cases. Disorders of complement regulation are, numerically, the most important. The outcome for children with atypical HUS is poor, and, because of the rarity of these disorders, clinical experience is scanty. Some cases of complement dysfunction appear to respond to plasma therapy. The therapeutic part of this guideline is the consensus of the contributing authors and is based on limited information from uncontrolled studies. The guideline proposes urgent and empirical plasmapheresis replacement with whole plasma fraction for the first month after diagnosis. This should only be undertaken in specialized pediatric nephrology centers where appropriate medical and nursing skills are available. The guideline includes defined terminology and audit points so that the early clinical effectiveness of the strategy can be evaluated.

A land surface scheme that may be run with or without a tiled representation of subgrid heterogeneity and includes an implicit atmospheric coupling scheme is described. Simulated average surface air temperatures and diurnal temperature ranges in a GCM using this surface model are compared with climatology. Surface tiling is not found to give a clear improvement in the simulated climate but offers more flexibility in the representation of heterogeneous land surface processes. Using the same meteorological forcing in offline simulations using versions of the surface model with and without tiling, the tiled model gives slightly lower winter temperatures at high latitudes and higher summer temperatures at midlatitudes. When the surface model is coupled to a GCM, reduced evaporation in the tiled version leads to changes in cloud cover and radiation at the surface that enhance these differences.

A spatially intensive survey in 1989 of 52 sites in the Red River drainage in southwest Oklahoma and surveys in all years from 1978 to 1987 on four sites in the drainage provided evidence that construction of Altus Dam on the North Fork of the Red River caused major changes in fish community structure in the river above the dam. Pre‐impoundment data on the fish communities were scanty, but the inferences they allowed were similar to those obtained by comparing fish assemblages in the North Fork above the dam with assemblages elsewhere in the drainage, particularly along Salt Fork, which had similar habitat characteristics. Twenty‐five species were collected in the North Fork above Altus Dam, compared to 33 in the Salt Fork and 34 in the North Fork below the dam. The speckled chub Macrhybopsis (formerly Hybopsis) aestivalis and the chub shiner Notropis potteri were absent in the North Fork above Altus Dam but fairly common in similar streams elsewhere in the area. The plains minnow Hybognathus placitus and the Red River shiner Notropis bairdi were among the most common fish species found in southwest Oklahoma, but were not collected above Altus Dam in the 1989 survey and were collected only intermittently and in small numbers in the long‐term survey. We speculate that these two species have repeatedly been extirpated and have been reestablished as bait‐bucket introductions since the dam was closed. Upstream of the reservoir, the sand shiner Notropis stramineus and the emerald shiner Notropis atherinoides replaced the plains minnow and the Red River shiner as dominant species, and several reservoir species were more common. Significant negative association at two long‐term sites suggested that the sand shiner and Red River shiner were filling similar niches.