Essence, Essence, and Essence

I argue that three different notions of essence—temporal, definitional, and modal—are all distinct notions, and are all philosophically useful. After defining the different notions, I discuss the philosophical problems each addresses

Protein-DNA Recognition Models for the Homeodomain and C2H2 Zinc Finger Transcription Factor Families

Transcription factors: TFs) play a central role in the gene regulatory network of each cell. They can stimulate or inhibit transcription of their target genes by binding to short, degenerate DNA sequence motifs. The goal of this research is to build improved models of TF binding site recognition. This can facilitate the determination of regulatory networks and also allow for the prediction of binding site motifs based only on the TF protein sequence. Recent technological advances have rapidly expanded the amount of quantitative TF binding data available. PBMs: Protein Binding Microarrays) have recently been implemented in a format that allows all 10mers to be assayed in parallel. There is now PBM data available for hundreds of transcription factors. Another fairly recent technique for determining the binding preference of a TF is an in vivo bacterial one-hybrid assay: B1H). In this approach a TF is expressed in E. coli where it can be used to select strong binding sites from a library of randomized sites located upstream of a weak promoter, driving expression of a selectable gene. When coupled with high throughput sequencing and a newly developed analysis method, quantitative binding data can be obtained. In the last few years, the binding specificities of hundreds of TFs have been determined using B1H. The two largest eukaryotic transcription factor families are the zf-C2H2 and homeodomain TF families. Newly available PBM and B1H specificity models were used to develop recognition models for these two families, with the goal of being able to predict the binding specific of a TF from its protein sequence. We developed a feature selection method based on adjusted mutual information that automatically recovers nearly all of the known key residues for the homeodomain and zf-C2H2 families. Using those features we find that, for both families, random forest: RF) and support vector machine: SVM) based recognition models outperform the nearest neighbor method, which has previously been considered the best method

Age Effects on Iron-Based Pipes in Water Distribution Systems

Pipes in water distribution systems may change as they age. The accumulation of corrosion byproducts and suspended particles on the inside wall of aged pipes can increase pipe roughness and reduce pipe diameter. To quantify the hydraulic effects of irregular accumulation on the pipe walls, eleven aged pipes ranging in diameter from 0.020-m (0.75-in) to 0.100-m (4-in) and with varying degrees of turberculation were located and subjected to laboratory testing. The laboratory test results were used to determine a relationship between pipe diameter reduction and Hazen-Williams C. This relationship, combined with a manipulation of the Hazen-Williams equation, provided a simple and direct method for correcting the diameters of aged pipes in distribution models. Using EPANET 2, the importance of correcting pipe diameters when modeling water distribution systems containing aged pipes was investigated. Correcting the pipe diameters in the sample network reduced the modeled water age by up to 10% and changed the pattern of fluctuating water age that occurred as waters with different sources moved through the pipe network. In addition, two of the aforementioned aged pipes with diameters of 0.025-m (1-in) and 0.050-m (2-in) were modeled using Reynolds-Averaged Navier-Stokes (RANS) turbulence modeling. Flow was computed at Reynolds numbers ranging from 6700 to 31,000 using three turbulence models including a 4-equation v2-f model, and 2-equation realizable k-e; and k-ω models. In comparing the RANS results to the laboratory testing, the v2-f model was found to be most accurate, producing Darcy-Weisbach friction factors from 5% higher to 15% lower than laboratory-obtained values. The capability of RANS modeling to provide a detailed characterization of the flow in aged pipes was demonstrated. Large eddy simulation (LES) was also performed on a single 0.050-m (2-in) pipe at a Reynolds number of 6800. The Darcy-Weisbach friction factor calculated using LES was 20% less than obtained from experimental tests. Roughness elements smaller than the grid scale and deficiencies in the subgrid-scale model at modeling the complex three-dimensional flow structures due to the irregular pipe boundary were identified as likely sources of error. Even so, the utility of LES for describing complex flows was established

B cells at the interface of innate and adaptive immunity in systemic lupus erythematosus: requirements for the activation of autoreactive B cells in autoimmune disease

Systemic autoimmune disease is characterized by loss of immunologic tolerance to a restricted set of self-nuclear antigens. These macromolecular complexes can be grouped into two categories: DNA-containing autoantigens such as chromatin, and RNA containing autoantigens such as Smith antigen (Sm) and related ribonucleoprotein complexes. Elucidating the mechanism for selective targeting of these molecules in systemic lupus erythematosus (SLE) may provide clues to the etiology of disease. We hypothesized that Toll-like receptors (TLRs), germline-encoded pattern-recognition receptors of the innate immune system, could dictate target antigen specificity in SLE. Using genetic ablation of various TLRs in murine models of SLE, we have demonstrated that TLRs are critical for directing the autoimmune response against canonical nuclear autoantigens.In the absence of TLR9, a receptor for CpG sequence motifs in DNA, the generation of autoantibodies to DNA-containing antigens was specifically inhibited. Other autoantibodies specific for RNA-containing antigens were maintained or even increased in TLR9-deficient autoimmune mice. We then investigated whether TLR3, a receptor for double-stranded RNA, or TLR7, a receptor for single-stranded RNA, were required for the generation of autoantibodies to RNA-containing antigens. While TLR3 did not appear to affect autoantibody production, the absence of TLR7 led to a reduction in anti-ribonucleoprotein antibodies. Genetic deletion of these receptors also had dramatic, but opposing, effects on disease progression. TLR9-deficient mice developed exacerbated disease and systemic inflammation with accelerated mortality, while TLR7-deficient mice had ameliorated clinical disease and decreased immune activation. A critical component of disease pathogenesis in these mice appeared to be the activation of type I interferon-producing plasmacytoid dendritic cells (pDCs), which was increased in the absence of TLR9, but decreased in the absence of TLR7.Further studies on the mechanism of autoantibody production and pDC activation revealed that TLR9 expression within B cells was required for anti-DNA antibody production, and that circulating serum factors generated in the absence of TLR9 could induce interferon production by pDCs. We have also shown that costimulation by CD4+ helper T cells contributes to autoantibody production in SLE. Integration of innate and adaptive activation signals is thus central to B cell autoantibody production and clinical disease progression in SLE

Mix Design for a Concrete Canoe

Each year the American Society of Civil Engineers sponsors a concrete canoe competition. This paper details the work performed by Ryan Christensen for the 2006 concrete canoe competition. His primary focus was on formulating a concrete mix to be used for the Utah State University canoe. Basic information regarding the building and design of concrete canoes is also presented. Finally, general competition results for 2006 are presented for the Utah State University canoe team

Phytoplankton Community and Algal Toxicity at a Recurring Bloom in Sullivan Bay, Kabetogama Lake, Minnesota, USA

Kabetogama Lake in Voyageurs National Park, Minnesota, USA suffers from recurring late summer algal blooms that often contain toxin-producing cyanobacteria. Previous research identified the toxin microcystin in blooms, but we wanted to better understand how the algal and cyanobacterial community changed throughout an open water season and how changes in community structure were related to toxin production. Therefore, we sampled one recurring bloom location throughout the entire open water season. The uniqueness of this study is the absence of urban and agricultural nutrient sources, the remote location, and the collection of samples before any visible blooms were present. Through quantitative polymerase chain reaction (qPCR), we discovered that toxin-forming cyanobacteria were present before visible blooms and toxins not previously detected in this region (anatoxin-a and saxitoxin) were present, indicating that sampling for additional toxins and sampling earlier in the season may be necessary to assess ecosystems and human health risk

The acute effects of various types of stretching (static, dynamic, ballistic, and no stretch) of the iliopsoas on 40-yard sprint times in non-athletes

The purpose of this study was to determine the effect of static, ballistic, dynamic, and no stretching immediately prior to a 40-yard sprint in college students. There were 35 healthy subjects (22 male and 13 female) between the ages of 24 and 37 (Mean = 26.46 yrs, SD = 2.99 yrs) who participated. The experiment consisted of running 4, 40-yard sprint trials immediately following 1 of 4 different stretching protocols. Prior to each 40- yard sprint trial, a 5-minute warm up was performed at 3.5 mph on a treadmill. Each subject received each of the four techniques in a randomized order and ran a baseline sprint prior to each stretching protocol. In each protocol, subjects received one of four stretching techniques: ballistic, dynamic, static, no stretch and immediately ran a timed 40-yard sprint post stretch. The trials were completed within a 2 week time period allowing 48-72 hours between each trial. In the no stretch condition, subjects improved significantly from pre to post sprint times (

The Effect of Training on Novice Raters When Performing Radiographic Measurement of Humeral Retroversion: a Follow-up Study

Background and Purpose: Humeral retroversion angle (HRVA) is the angle between the proximal humeral axis and the distal humeral axis. HRVA is significantly higher in the dominant shoulder for individuals that partake in increased overhead activities. CT scans are recognized as the gold standard for measuring HRVA, although current literature is investigating the use of radiographs to measure HRVA as a more cost-effective method. The purpose of this study was to determine if there is a training effect in the ability to measure HRVA on radiographs as determined by physical therapy students. Methods: Four second-year Doctor of Physical Therapy students measured HRVA on 35 shoulder radiographs on two separate occasions. Two of the students received training (trained group) from an experienced HRVA investigator which included written and verbal instruction on how to obtain HRVA measurements. Training also included HRVA measurement practice sessions with feedback from the experienced HRVA investigator prior to data collection. The other two students (untrained group) were provided only written instructions on how to obtain HRVA measurements. The experienced HRVA investigator served as the gold standard. Results: There was minimal difference in the HRVA measurements between the trained and untrained groups with the individuals in both groups demonstrating excellent intra-rater reliability. The intra-rater reliability was 0.89 and 0.87 for the trained group members and 0.89 and 0.89 for the untrained group members, respectively. In addition, the inter-rater reliability between the trained and untrained groups in comparison to the experienced clinician was also minimal. The combined inter-rater reliability for the trained group was 0.82 and untrained group was 0.80. Conclusion: Novice physical therapy students can accurately measure HRVA on radiographs with written instruction and no other formal training. This demonstrates the potential to further incorporate radiographic information into clinical practice. This supports the APTA’s Vision 2020 for physical therapists to become autonomous practitioners and expand the physical therapy scope of practice