Comparison of brain–computer interface decoding algorithms in open-loop and closed-loop control

Neuroprosthetic devices such as a computer cursor can be controlled by the activity of cortical neurons when an appropriate algorithm is used to decode motor intention. Algorithms which have been proposed for this purpose range from the simple population vector algorithm (PVA) and optimal linear estimator (OLE) to various versions of Bayesian decoders. Although Bayesian decoders typically provide the most accurate off-line reconstructions, it is not known which model assumptions in these algorithms are critical for improving decoding performance. Furthermore, it is not necessarily true that improvements (or deficits) in off-line reconstruction will translate into improvements (or deficits) in on-line control, as the subject might compensate for the specifics of the decoder in use at the time. Here we show that by comparing the performance of nine decoders, assumptions about uniformly distributed preferred directions and the way the cursor trajectories are smoothed have the most impact on decoder performance in off-line reconstruction, while assumptions about tuning curve linearity and spike count variance play relatively minor roles. In on-line control, subjects compensate for directional biases caused by non-uniformly distributed preferred directions, leaving cursor smoothing differences as the largest single algorithmic difference driving decoder performance.     

Oxime esters as selective,covalent inhibitors of the serine hydrolase retinoblastoma-binding protein 9 (RBBP9)

We recently described a fluorescence polarization platform for competitive activity-based protein profiling (fluopol-ABPP) that enables high-throughput inhibitor screening for enzymes with poorly characterized biochemical activity. Here, we report the discovery of a class of oxime ester inhibitors for the unannotated serine hydrolase RBBP9 from a full-deck (200,000+ compound) fluopol-ABPP screen conducted in collaboration with the Molecular Libraries Screening Center Network (MLSCN). We show that these compounds covalently inhibit RBBP9 by modifying enzyme’s active site serine nucleophile and, based on competitive ABPP in cell and tissue proteomes, are selective for RBBP9 relative to other mammalian serine hydrolases.     

Febrile response and decrease in circulating lymphocytes following acute infection of white-tailed deer fawns with either a BVDV1 or a BVDV2 strain

Although commonly associated with infection in cattle, bovine viral diarrhea viruses (BVDV) also replicate in many domestic and wildlife species, including cervids. Bovine viral diarrhea viruses have been isolated from a number of cervids, including mule deer (Odocoileus hemionus), European roe deer (Capreolus capreolus), red deer (Cervus elaphus), white-tailed deer (Odocoileus virginianus), and mouse deer (Tragulus javanicus), but little information is available regarding clinical presentation and progression of infection in these species. In preliminary studies of experimental infection of deer with BVDV, researchers noted seroconversion but no clinical signs. In this study, we infected white-tailed deer fawns that were negative for BVDV and for antibodies against BVDV, with either a type 1 or a type 2 BVDV that had been isolated from white-tailed deer. Fawns were monitored for changes in basal temperature, circulating lymphocytes, and platelets. The clinical progression following inoculation in these fawns was similar to that seen with BVDV infections in cattle and included fever and depletion of circulating lymphocytes. Because free-ranging cervid populations are frequently in contact with domestic cattle in the United States, possible transfer of BVDV between cattle and cervids has significant implications for proposed BVDV control programs.     

Separation and enrichment of neural stem cells using segregation in an expanded bed

An expanded bed system has been developed for a novel application in which the separation and enrichment of neural stem cells from a sample containing a mixture of stem and progenitor cells is achieved based on the difference in the sizes of the aggregates of these types of cells. Inert Sephadex beads and flocculated yeast cells were used as experimental controls and references. The characteristics of the separation of neural stem cell aggregates based on size are similar to those achieved with flocculated yeast where cell-to-cell aggregation controls the pattern of size separation different from those of inert Sephadex beads.     

Increasing isolation reduces predator:prey species richness ratios in aquatic food webs

The number of species that live in a habitat typically declines as that habitat becomes more isolated. However, the influence of habitat isolation on patterns of food web structure, in particular the ratio of predator to prey species richness, is less well understood. We placed aquatic mesocosms at varying distances from ponds that acted as sources of potential colonists; then we examined how isolation affected the ratio of predator:prey species richness in the communities that assembled. In the final sampling, a total of 21 species (12 prey and 9 predators) of insects, crustaceans, and amphibians had colonized the mesocosms. We found that total species richness, as well as the richness of predators and prey, declined with increasing isolation. However, predator richness declined more rapidly than prey richness with increasing isolation, which lead to decreasing predator:prey ratios. This result conflicts with prior demonstrations of invariant predator:prey ratios in freshwater communities.     

Borna disease virus matrix protein is an integral component of the viral ribonucleoprotein complex that does not interfere with polymerase activity

We have recently shown that the matrix protein M of Borna disease virus (BDV) copurifies with the affinity-purified nucleoprotein (N) from BDV-infected cells, suggesting that M is an integral component of the viral ribonucleoprotein complex (RNP). However, further studies were hampered by the lack of appropriate tools. Here we generated an M-specific rabbit polyclonal antiserum to investigate the intracellular distribution of M as well as its colocalization with other viral proteins in BDV-infected cells. Immunofluorescence analysis revealed that M is located both in the cytoplasm and in nuclear punctate structures typical for BDV infection. Colocalization studies indicated an association of M with nucleocapsid proteins in these nuclear punctate structures. In situ hybridization analysis revealed that M also colocalizes with the viral genome, implying that M associates directly with viral RNPs. Biochemical studies demonstrated that M binds specifically to the phosphoprotein P but not to N. Binding of M to P involves the N terminus of P and is independent of the ability of P to oligomerize. Surprisingly, despite P-M complex formation, BDV polymerase activity was not inhibited but rather slightly elevated by M, as revealed in a minireplicon assay. Thus, unlike M proteins of other negative-strand RNA viruses, BDV-M seems to be an integral component of the RNPs without interfering with the viral polymerase activity. We propose that this unique feature of BDV-M is a prerequisite for the establishment of BDV persistence.     

Oligonucleotide fingerprint identification for microarray-based pathogen diagnostic assays

MOTIVATION: Advances in DNA microarray technology and computational methods have unlocked new opportunities to identify 'DNA fingerprints', i.e. oligonucleotide sequences that uniquely identify a specific genome. We present an integrated approach for the computational identification of DNA fingerprints for design of microarray-based pathogen diagnostic assays. We provide a quantifiable definition of a DNA fingerprint stated both from a computational as well as an experimental point of view, and the analytical proof that all in silico fingerprints satisfying the stated definition are found using our approach. RESULTS: The presented computational approach is implemented in an integrated high-performance computing (HPC) software tool for oligonucleotide fingerprint identification termed TOFI. We employed TOFI to identify in silico DNA fingerprints for several bacteria and plasmid sequences, which were then experimentally evaluated as potential probes for microarray-based diagnostic assays. Results and analysis of approximately 150 in silico DNA fingerprints for Yersinia pestis and 250 fingerprints for Francisella tularensis are presented. AVAILABILITY: The implemented algorithm is available upon request.     

Exotic grasses and nitrate enrichment alter soil carbon cycling along an urban–rural tropical forest gradient

Urban areas are expanding rapidly in tropical regions, with potential to alter ecosystem dynamics. In particular, exotic grasses and atmospheric nitrogen (N) deposition simultaneously affect tropical urbanized landscapes, with unknown effects on properties like soil carbon (C) storage. We hypothesized that (H1) soil nitrate (NO₃^?) is elevated nearer to the urban core, reflecting N deposition gradients. (H2) Exotic grasslands have elevated soil NO₃^? and decreased soil C relative to secondary forests, with higher N promoting decomposer activity. (H3) Exotic grasslands have greater seasonality in soil NO₃^? vs. secondary forests, due to higher sensitivity of grassland soil moisture to rainfall. We predicted that NO₃^? would be positively related to dissolved organic C (DOC) production via changes in decomposer activity. We measured six paired grassland/secondary forest sites along a tropical urban‐to‐rural gradient during the three dominant seasons (hurricane, dry, and early wet). We found that (1) soil NO₃^? was generally elevated nearer to the urban core, with particularly clear spatial trends for grasslands. (2) Exotic grasslands had lower soil C than secondary forests, which was related to elevated decomposer enzyme activities and soil respiration. Unexpectedly, soil NO₃^? was negatively related to enzyme activities, and was lower in grasslands than forests. (3) Grasslands had greater soil NO₃^? seasonality vs. forests, but this was not strongly linked to shifts in soil moisture or DOC. Our results suggest that exotic grasses in tropical regions are likely to drastically reduce soil C storage, but that N deposition may have an opposite effect via suppression of enzyme activities. However, soil NO₃^? accumulation here was higher in urban forests than grasslands, potentially related to of aboveground N interception. Net urban effects on C storage across tropical landscapes will likely vary depending on the mosaic of grass cover, rates of N deposition, and responses by local decomposer communities.