An Intensive Archaeological Survey of Potential Cooling Ponds for Pen Branch and Four Mile Creek, Savannah River Plant, Aiken and Barnwell Counties, South Carolina

https://scholarcommons.sc.edu/archanth_books/1189/thumbnail.jp

A Novel Interdisciplinary Course in Gerontechnology for Disseminating Computational Thinking

While specialized knowledge and skills are the hallmark of modern society, the size and complexity of contemporary problems often require cooperative effort to analyze and solve. Therefore, experiences with skills, methodologies, and tools for effective interdisciplinary collaboration and structured problem solving are vital for preparing students for future academic and professional success. Meanwhile, computational systems have permeated much of modern professional and personal life, making computational thinking an essential skill for members of modern society. However, formal training in these techniques is primarily limited to students within computer science, mathematics, management of information systems, and engineering. At Iowa State University, we have designed and offered an experimental course to develop undergraduate students’ abilities for interdisciplinary teamwork and to disseminate computational thinking skills to a broader range of students. This novel course was jointly designed and instructed by faculty from the Computer Science Department, Gerontology Program, and Graphic Design Program to incorporate diverse faculty expertise and pedagogical approaches. Students were required to interview real users to identify real-life problems, gather requirements, and assess candidate solutions, which necessitated communication both within the group and with technologically-disinclined users. In-class presentations and wiki-based project websites provided regular practice at disseminating domain expertise to larger interdisciplinary audiences. Workshops, group-based mentoring, peer learning, and guided discovery allowed non-CS majors to learn much more about computer programs and tools, and grading criteria held students individually accountable within their disciplines but also emphasized group collaboration

\u27It Could be Worse ... Lot\u27s Worse!\u27 Why Health-Related Quality of Life is Better in Older Compared with Younger Individuals with Heart Failure

Background: health-related quality of life (HRQOL) is markedly impaired in patients with heart failure (HF). Despite worse prognosis and physical status, older patients have better HRQOL than younger patients. Objective: to determine reasons for differences in HRQOL in older compared with younger HF patients. Methods: a mixed methods approach was used. HRQOL was assessed using the Minnesota Living with HF Questionnaire and compared among HF patients (n = 603) in four age groups (≤53, 54–62, 63–70 and ≥71 years). Socio-demographic/clinical and psychological factors related to HRQOL were determined in four groups using multiple regressions. Patients (n = 20) described their views of HRQOL during semi-structured interviews. Results: HRQOL was worse in the youngest group, and best in the two oldest groups. The youngest group reported higher levels of depression and anxiety than the oldest group. Anxiety, depression and functional capacity predicted HRQOL in all age groups. Qualitatively, patients in all age groups acknowledged the negative impact of HF on HRQOL; nonetheless older patients reported that their HRQOL exceeded their expectations for their age. Younger patients bemoaned the loss of activities and roles, and reported their HRQOL as poor. Conclusions: better HRQOL among older HF patients is the result, in part, of better psychosocial status. The major factor driving better HRQOL among older patients is a change with advancing age in expectations about what constitutes good HRQOL

Identification of Symptom Clusters among Patients with Heart Failure: An International Observational Study

BACKGROUND: Virtually all patients with heart failure experience multiple symptoms simultaneously, yet clinicians and researchers usually consider symptoms in isolation. Recognizing and responding early to escalating symptoms is essential to preventing hospitalizations in heart failure, yet patients have considerable difficulty recognizing symptoms. Identification of symptom clusters could improve symptom recognition, but cultural differences may be present that must be considered. OBJECTIVES: To identify and compare symptom clusters in heart failure patients from the United States, Europe and Asia. DESIGN: Cross-sectional, observational study. SETTINGS: In- and out-patient settings in three regions of the world: Asia (i.e., China and Taiwan); Europe (i.e., the Netherlands and Sweden); and the United States. PARTICIPANTS: A total of 720 patients with confirmed heart failure. Propensity scoring using New York Heart Association Classification was used to match participants from each of the three regions. METHODS: Symptoms were identified using the Minnesota Living with Heart Failure Questionnaire. To identify symptom clusters we used cluster analysis with the hierarchical cluster agglomerative approach. We used the Euclidean distance to measure the similarity of variables. Proximity between groups of variables was measured using Ward\u27s method. The resulting clusters were displayed with dendrograms, which show the proximity of variables to each other on the basis of semi-partial R-squared scores. RESULTS: There was a core group of symptoms that formed two comparable clusters across the countries. Dyspnea, difficulty in walking or climbing, fatigue/increased need to rest, and fatigue/low energy were grouped into a cluster, which was labeled as a physical capacity symptom cluster. Worrying, feeling depressed, and cognitive problems were grouped into a cluster, which was labeled as an emotional/cognitive symptom cluster. The symptoms of edema and trouble sleeping were variable among the countries and fell into different clusters. CONCLUSION: Despite the diversity in cultures studied, we found that symptoms clustered similarly among the cultural groups. Identification of similar symptoms clusters among patients with heart failure may improve symptom recognition in both patients and healthcare providers

AntiJen: a quantitative immunology database integrating functional, thermodynamic, kinetic, biophysical, and cellular data

AntiJen is a database system focused on the integration of kinetic, thermodynamic, functional, and cellular data within the context of immunology and vaccinology. Compared to its progenitor JenPep, the interface has been completely rewritten and redesigned and now offers a wider variety of search methods, including a nucleotide and a peptide BLAST search. In terms of data archived, AntiJen has a richer and more complete breadth, depth, and scope, and this has seen the database increase to over 31,000 entries. AntiJen provides the most complete and up-to-date dataset of its kind. While AntiJen v2.0 retains a focus on both T cell and B cell epitopes, its greatest novelty is the archiving of continuous quantitative data on a variety of immunological molecular interactions. This includes thermodynamic and kinetic measures of peptide binding to TAP and the Major Histocompatibility Complex (MHC), peptide-MHC complexes binding to T cell receptors, antibodies binding to protein antigens and general immunological protein-protein interactions. The database also contains quantitative specificity data from position-specific peptide libraries and biophysical data, in the form of diffusion co-efficients and cell surface copy numbers, on MHCs and other immunological molecules. The uses of AntiJen include the design of vaccines and diagnostics, such as tetramers, and other laboratory reagents, as well as helping parameterize the bioinformatic or mathematical in silico modeling of the immune system. The database is accessible from the URL:

Leptin is a four-helix bundle: secondary structure by NMR

AbstractLeptin is a signaling protein that in its mutant forms has been associated with obesity and Type II diabetes. The lack of sequence similarity has precluded analogies based on structural resemblance to known systems. Backbone NMR signals for mouse leptin (13C/15N -labeled) have been assigned and its secondary structure reveals it to be a four-helix bundle cytokine. Helix lengths and disulfide pattern are in agreement with leptin as a member of the short-helix cytokine family. A three-dimensional model was built verifying the mechanical consistency of the identified elements with a short-helix cytokine core

Adaptive changes in HIV-1 subtype C proteins during early infection are driven by changes in HLA-associated immune pressure

It is unresolved whether recently transmitted human immunodeficiency viruses (HIV) have genetic features that specifically favour their transmissibility. To identify potential "transmission signatures", we compared 20 full-length HIV-1 subtype C genomes from primary infections, with 66 sampled from ethnically and geographically matched individuals with chronic infections. Controlling for recombination and phylogenetic relatedness, we identified 39 sites at which amino acid frequency spectra differed significantly between groups. These sites were predominantly located within Env, Pol and Gag (14/39, 9/39 and 6/39 respectively) and were significantly clustered (33/39) within known immunoreactive peptides. Within 6 months of infection, we detected reversion-to-consensus mutations at 14 sites and potential CTL escape mutations at seven. Here we provide evidence that frequent reversion mutations probably allows the virus to recover replicative fitness which, together with immune escape driven by the HLA alleles of the new hosts, differentiate sequences from chronic infections from those sampled shortly after transmission

Moving biochemistry and molecular biology courses online in times of disruption: Recommended practices and resources ‐ a collaboration with the faculty community and ASBMB

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163423/2/bmb21354_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163423/1/bmb21354.pd

Anti-inflammatory activity and neutrophil reductions mediated by the JAK1/JAK3 inhibitor, CP-690,550, in rat adjuvant-induced arthritis

<p>Abstract</p> <p>Background</p> <p>The Janus kinase (JAK) family of tyrosine kinases includes JAK1, JAK2, JAK3 and TYK2, and is required for signaling through Type I and Type II cytokine receptors. CP-690,550 is a potent and selective JAK inhibitor currently in clinical trials for rheumatoid arthritis (RA) and other autoimmune disease indications. In RA trials, dose-dependent decreases in neutrophil counts (PBNC) were observed with CP-690,550 treatment. These studies were undertaken to better understand the relationship between JAK selectivity and PBNC decreases observed with CP-690,550 treatment.</p> <p>Methods</p> <p>Potency and selectivity of CP-690,550 for mouse, rat and human JAKs was evaluated in a panel of <it>in vitro </it>assays. The effect of CP-690,550 on granulopoiesis from progenitor cells was also assessed <it>in vitro </it>using colony forming assays. <it>In vivo </it>the potency of orally administered CP-690,550 on arthritis (paw edema), plasma cytokines, PBNC and bone marrow differentials were evaluated in the rat adjuvant-induced arthritis (AIA) model.</p> <p>Results</p> <p>CP-690,550 potently inhibited signaling through JAK1 and JAK3 with 5-100 fold selectivity over JAK2 in cellular assays, despite inhibiting all four JAK isoforms with nM potency in <it>in vitro </it>enzyme assays. Dose-dependent inhibition of paw edema was observed <it>in vivo </it>with CP-690,550 treatment. Plasma cytokines (IL-6 and IL-17), PBNC, and bone marrow myeloid progenitor cells were elevated in the context of AIA disease. At efficacious exposures, CP-690,550 returned all of these parameters to pre-disease levels. The plasma concentration of CP-690,550 at efficacious doses was above the <it>in vitro </it>whole blood IC50 of JAK1 and JAK3 inhibition, but not that of JAK2.</p> <p>Conclusion</p> <p>Results from this investigation suggest that CP-690,550 is a potent inhibitor of JAK1 and JAK3 with potentially reduced cellular potency for JAK2. In rat AIA, as in the case of human RA, PBNC were decreased at efficacious exposures of CP-690,550. Inflammatory end points were similarly reduced, as judged by attenuation of paw edema and cytokines IL-6 and IL-17. Plasma concentration at these exposures was consistent with inhibition of JAK1 and JAK3 but not JAK2. Decreases in PBNC following CP-690,550 treatment may thus be related to attenuation of inflammation and are likely not due to suppression of granulopoiesis through JAK2 inhibition.</p

A One Health overview, facilitating advances in comparative medicine and translational research.

Table of contentsA1 One health advances and successes in comparative medicine and translational researchCheryl StroudA2 Dendritic cell-targeted gorilla adenoviral vector for cancer vaccination for canine melanomaIgor Dmitriev, Elena Kashentseva, Jeffrey N. Bryan, David T. CurielA3 Viroimmunotherapy for malignant melanoma in the companion dog modelJeffrey N. Bryan, David Curiel, Igor Dmitriev, Elena Kashentseva, Hans Rindt, Carol Reinero, Carolyn J. HenryA4 Of mice and men (and dogs!): development of a commercially licensed xenogeneic DNA vaccine for companion animals with malignant melanomaPhilip J. BergmanA5 Successful immunotherapy with a recombinant HER2-expressing Listeria monocytogenes in dogs with spontaneous osteosarcoma paves the way for advances in pediatric osteosarcomaNicola J. Mason, Josephine S. Gnanandarajah, Julie B. Engiles, Falon Gray, Danielle Laughlin, Anita Gaurnier-Hausser, Anu Wallecha, Margie Huebner, Yvonne PatersonA6 Human clinical development of ADXS-HER2Daniel O'ConnorA7 Leveraging use of data for both human and veterinary benefitLaura S. TremlA8 Biologic replacement of the knee: innovations and early clinical resultsJames P. StannardA9 Mizzou BioJoint Center: a translational success storyJames L. CookA10 University and industry translational partnership: from the lab to commercializationMarc JacobsA11 Beyond docking: an evolutionarily guided OneHealth approach to drug discoveryGerald J. Wyckoff, Lee Likins, Ubadah Sabbagh, Andrew SkaffA12 Challenges and opportunities for data applications in animal health: from precision medicine to precision husbandryAmado S. GuloyA13 A cloud-based programmable platform for healthHarlen D. HaysA14 Comparative oncology: One Health in actionAmy K. LeBlancA15 Companion animal diseases bridge the translational gap for human neurodegenerative diseaseJoan R. Coates, Martin L. Katz, Leslie A. Lyons, Gayle C. Johnson, Gary S. Johnson, Dennis P. O'BrienA16 Duchenne muscular dystrophy gene therapyDongsheng DuanA17 Polycystic kidney disease: cellular mechanisms to emerging therapiesJames P. CalvetA18 The domestic cat as a large animal model for polycystic kidney diseaseLeslie A. Lyons, Barbara GandolfiA19 The support of basic and clinical research by the Polycystic Kidney Disease FoundationDavid A. BaronA20 Using naturally occurring large animal models of human disease to enable clinical translation: treatment of arthritis using autologous stromal vascular fraction in dogsMark L. WeissA21 Regulatory requirements regarding clinical use of human cells, tissues, and tissue-based productsDebra A. WebsterA22 Regenerative medicine approaches to Type 1 diabetes treatmentFrancis N. KaranuA23 The zoobiquity of canine diabetes mellitus, man's best friend is a friend indeed-islet transplantationEdward J. RobbA24 One Medicine: a development model for cellular therapy of diabetesRobert J. Harman