Kinetic Mechanism for Single stranded DNA binding and Translocation by S. cerevisiae Isw2

The chromatin remodeling complex Isw2 from S. cerevisiae (yIsw2) mobilizes nucleosomes through an ATP-dependent reaction that is coupled to the translocation of the helicase domain of the enzyme along intranucleosomal DNA. In this study we demonstrate that yIsw2 is capable of translocating along single-stranded DNA in a reaction that is coupled to ATP hydrolysis. We propose that single-stranded DNA translocation by yIsw2 occurs through a series of repeating uniform steps with an overall macroscopic processivity of P = (0.90 ± 0.02), corresponding to an average translocation distance of (20 ± 2) nucleotides before dissociation. This processivity corresponds well to the processivity of nucleosome sliding by yIsw2 thus arguing that single-stranded DNA translocation or tracking may be fundamental to the double-stranded DNA translocation required for effective nucleosome mobilization. Furthermore, we find evidence that a slow initiation process, following DNA binding, may be required to make yIsw2 competent for DNA translocation. We also provide evidence that this slow initiation process may correspond to the second step of a two-step DNA binding mechanism by yIsw2 and a quantitative description of the kinetics of this DNA binding mechanism

Drive-by scour monitoring of railway bridges using a wavelet-based approach

This paper numerically investigates the feasibility of using bogie acceleration measurements from a passing train to detect the presence of bridge scour. The Continuous Wavelet Transform is used to process the simulated acceleration measurements for a number of train passages over a scoured bridge, with scour represented as a local reduction in stiffness at a given pier. Average Wavelet coefficients are calculated for a batch of train runs passing over the same bridge. A scour indicator is developed as the difference in average coefficients between batches from the healthy bridge and when the bridge is damaged by scour. The method is assessed using a blind test, whereby one author simulated trains passing over a bridge in various states of health. The remaining authors were provided only with the train accelerations and had to predict the state of scour without any prior knowledge. This scour indicator performed quite well in the blind test for normal vehicle operating conditions

Dental Students’ Perceived Value of Peer‐Mentoring Clinical Leadership Experiences

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153637/1/jddj002203372016803tb06086x.pd

Management of bovine tuberculosis in Michigan wildlife: Current status and near term prospects

Surveillance and control activities for bovine tuberculosis (bTB) in free-ranging Michigan white-tailed deer (Odocoileus virginianus) have now been underway for over a decade. Significant progress has been made, lowering apparent prevalence in deer in the core area by >60%, primarily via reduction of deer densities through hunting, and restrictions on public feeding and baiting of deer. These broad strategies of the Michigan Department of Natural Resources (MDNR), implemented with the cooperation of Michigan deer hunters, halved the deer population in the bTB endemic area. However, as hunters see fewer deer, their willingness to sustain aggressive harvests has waned, and public resentment of control measures has grown. During the past four years, apparent prevalence in core area deer has held approximately steady just below 2%. After bottoming out in 2004 at an estimated 10–12 deer/km2, deer numbers have since rebounded by ∼30%. Public compliance with baiting and feeding restrictions has been variable. In general, hunters in the core area do not perceive bTB as a problem, in spite of 13 years of MDNR outreach. To date, MDNR has expended more than US$23 million on TB-related activities. Of late, a substantial portion of that funding has been diverted to support other programs which have suffered from budget shortfalls. Livestock herd breakdowns continue to occur sporadically, averaging 3–4 per year 2005 to present. In total, 46 cattle and 4 captive deer herds have been diagnosed bTB positive statewide, the majority yielding only 1 positive animal. Five cattle herds were twice infected, one thrice. Michigan Department of Agriculture (MDA) policy emphasis has shifted towards obtaining producer support for wildlife risk mitigation and farm biosecurity. Funding has proven a limiting factor, with the majority of the US$63 million spent to date devoted to whole herd testing. Nevertheless, some initiatives justify cautious optimism. Promising research to support eventual vaccination of wild deer continues. Some hunters and landowners have begun to recognize the costs of high deer densities and supplemental feeding. A peninsula-wide ban on baiting and feeding was enacted. Some cattle producers, recognizing their precarious circumstances, have begun work to change long-held prevailing opinions among their peers about farm biosecurity. Yet formidable challenges remain, and evidence suggests that eradication of bTB, if it can be achieved, will take decades, and will require greater public and political resolve than has been demonstrated thus far

Ultrasound-triggered antibiotic release from PEEK clips to prevent spinal fusion infection: Initial evaluations.

Despite aggressive peri-operative antibiotic treatments, up to 10% of patients undergoing instrumented spinal surgery develop an infection. Like most implant-associated infections, spinal infections persist through colonization and biofilm formation on spinal instrumentation, which can include metal screws and rods for fixation and an intervertebral cage commonly comprised of polyether ether ketone (PEEK). We have designed a PEEK antibiotic reservoir that would clip to the metal fixation rod and that would achieve slow antibiotic release over several days, followed by a bolus release of antibiotics triggered by ultrasound (US) rupture of a reservoir membrane. We have found using human physiological fluid (synovial fluid), that higher levels (100–500 μg) of vancomycin are required to achieve a marked reduction in adherent bacteria vs. that seen in the common bacterial medium, trypticase soy broth. To achieve these levels of release, we applied a polylactic acid coating to a porous PEEK puck, which exhibited both slow and US-triggered release. This design was further refined to a one-hole or two-hole cylindrical PEEK reservoir that can clip onto a spinal rod for clinical use. Short-term release of high levels of antibiotic (340 ± 168 μg), followed by US-triggered release was measured (7420 ± 2992 μg at 48 h). These levels are sufficient to prevent adhesion of Staphylococcus aureus to implant materials. This study demonstrates the feasibility of an US-mediated antibiotic delivery device, which could be a potent weapon against spinal surgical site infection. Statement of Significance: Spinal surgical sites are prone to bacterial colonization, due to presence of instrumentation, long surgical times, and the surgical creation of a dead space (≥5 cm 3 ) that is filled with wound exudate. Accordingly, it is critical that new approaches are developed to prevent bacterial colonization of spinal implants, especially as neither bulk release systems nor controlled release systems are available for the spine. This new device uses non-invasive ultrasound (US) to trigger bulk release of supra-therapeutic doses of antibiotics from materials commonly used in existing surgical implants. Thus, our new delivery system satisfies this critical need to eradicate surviving bacteria, prevent resistance, and markedly lower spinal infection rates

An Optimal Linear Time Algorithm for Quasi-Monotonic Segmentation

Monotonicity is a simple yet significant qualitative characteristic. We consider the problem of segmenting a sequence in up to K segments. We want segments to be as monotonic as possible and to alternate signs. We propose a quality metric for this problem using the l_inf norm, and we present an optimal linear time algorithm based on novel formalism. Moreover, given a precomputation in time O(n log n) consisting of a labeling of all extrema, we compute any optimal segmentation in constant time. We compare experimentally its performance to two piecewise linear segmentation heuristics (top-down and bottom-up). We show that our algorithm is faster and more accurate. Applications include pattern recognition and qualitative modeling.Comment: This is the extended version of our ICDM'05 paper (arXiv:cs/0702142

Trial-by-Trial Adjustments of Cognitive Control Following Errors and Response Conflict are Altered in Pediatric Obsessive Compulsive Disorder

Background: Impairments of cognitive control have been theorized to drive the repetitive thoughts and behaviors of obsessive compulsive disorder (OCD) from early in the course of illness. However, it remains unclear whether altered trial-by-trial adjustments of cognitive control characterize young patients. To test this hypothesis, we determined whether trial-by-trial adjustments of cognitive control are altered in children with OCD, relative to healthy controls. Methods: Forty-eight patients with pediatric OCD and 48 healthy youth performed the Multi-Source Interference Task. Two types of trial-by-trial adjustments of cognitive control were examined: post-error slowing (i.e., slower responses after errors than after correct trials) and post-conflict adaptation (i.e., faster responses in high-conflict incongruent trials that are preceded by other high-conflict incongruent trials, relative to low-conflict congruent trials). Results: While healthy youth exhibited both post-error slowing and post-conflict adaptation, patients with pediatric OCD failed to exhibit either of these effects. Further analyses revealed that patients with low symptom severity showed a reversal of the post-conflict adaptation effect, whereas patients with high symptom severity did not show any post-conflict adaptation. Conclusion: Two types of trial-by-trial adjustments of cognitive control are altered in pediatric OCD. These abnormalities may serve as early markers of the illness

How do lizard niches conserve, diverge or converge? Further exploration of saurian evolutionary ecology

Background: Environmental conditions on Earth are repeated in non-random patterns that often coincide with species from different regions and time periods having consistent combinations of morphological, physiological and behavioral traits. Observation of repeated trait combinations among species confronting similar environmental conditions suggest that adaptive trait combinations are constrained by functional tradeoffs within or across niche dimensions. In an earlier study, we assembled a high-resolution database of functional traits for 134 lizard species to explore ecological diversification in relation to five fundamental niche dimensions. Here we expand and further examine multivariate relationships in that dataset to assess the relative influence of niche dimensions on the distribution of species in 6-dimensional niche space and how these may deviate from distributions generated from null models. We then analyzed a dataset with lower functional-trait resolution for 1023 lizard species that was compiled from our dataset and a published database, representing most of the extant families and environmental conditions occupied by lizards globally. Ordinations from multivariate analysis were compared with null models to assess how ecological and historical factors have resulted in the conservation, divergence or convergence of lizard niches. Results: Lizard species clustered within a functional niche volume influenced mostly by functional traits associated with diet, activity, and habitat/substrate. Consistent patterns of trait combinations within and among niche dimensions yielded 24 functional groups that occupied a total niche space significantly smaller than plausible spaces projected by null models. Null model tests indicated that several functional groups are strongly constrained by phylogeny, such as nocturnality in the Gekkota and the secondarily acquired sit-and-wait foraging strategy in Iguania. Most of the widely distributed and species-rich families contained multiple functional groups thereby contributing to high incidence of niche convergence. Conclusions: Comparison of empirical patterns with those generated by null models suggests that ecological filters promote limited sets of trait combinations, especially where similar conditions occur, reflecting both niche convergence and conservatism. Widespread patterns of niche convergence following ancestral niche diversification support the idea that lizard niches are defined by trait-function relationships and interactions with environment that are, to some degree, predictable and independent of phylogeny.Fil: Pelegrin, Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Diversidad y Ecología Animal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto de Diversidad y Ecología Animal; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; ArgentinaFil: Winemiller, Kirk Owen. Texas A&M University; Estados UnidosFil: Vitt, Laurie J.. University Of Oklahoma; Estados UnidosFil: Fitzgerald, Daniel B.. United States Geological Survey; Estados UnidosFil: Pianka, Eric R. University of Texas at Austin; Estados Unido

Genetic Variants of Milk Proteins - Relevance to Milk Composition and Cheese Production.

End of Project ReportObjectives: (i) to develop rapid screening procedures for the determination of milk protein polymorphism (genetic variants) (ii) to determine the frequency distribution of milk protein genetic variants in a large population of Irish Holstein-Friesians and to determine if there was an association between κ-casein variant and milk yield and composition in this group of animals, and (iii) to make Cheddar and low-moisture part-skim Mozzarella cheese from different κ-casein genetic variant milks and to assess any effect on cheese yield, composition and functional characteristics. Conclusions:Analysis of 6,007 individual Irish Holstein-Friesian milks showed that the phenotype distribution of the κ-casein BB variant was very low at 1.98% compared to 53.07% for κ-casein AA and 44.95% for κ-casein AB. While no statistically significant associations were observed between κ-casein variant and milk yield and composition, κ-casein BB variant milks had superior rennet coagulation properties to that of the AA or AB variants. Generally, κ-casein variant had little effect on compositional attributes of cheese apart from FDM (fat in dry matter) which was significantly higher in cheeses from κ-casein BB milk than in those from κ-casein AA milk. Generally, κ-casein variant had no significant effects on either primary or secondary proteolysis, or on the sensory and/or textural characteristics of Cheddar or Mozzarella cheese throughout ripening; or on the functional characteristics (e.g. flow and stretch) of baked Mozzarella on storage for 90 days at 4°C. However, κ-casein BB variant milk gave significantly higher actual, and moisture adjusted yields of Cheddar and Mozzarella cheese than either κ-casein AB or AA variant milks. For example, the moisture adjusted Cheddar yield from κ-casein BB milk was 8.2% higher than from κ-casein AA milk. In the case of Mozzarella, the moisture adjusted yield was 12% higher. Based on the results, it is estimated that the actual yield of cheese in a plant producing 20,000 tonnes per year from κ-casein AA milk would increase to approximately 21,180 tonnes of Cheddar, or 21,780 tonnes of Mozzarella if made from κ-casein BB milk. Where κ-casein AB milk is used instead of κ-casein BB milk, the estimated yield of Mozzarella would increase to 21,580 tonnes.Department of Agriculture, Food and the Marin