Force sensor using changes in magnetic flux

A force sensor includes a magnetostrictive material and a magnetic field generator positioned in proximity thereto. A magnetic field is induced in and surrounding the magnetostrictive material such that lines of magnetic flux pass through the magnetostrictive material. A sensor positioned in the vicinity of the magnetostrictive material measures changes in one of flux angle and flux density when the magnetostrictive material experiences an applied force that is aligned with the lines of magnetic flux

Design of Novel Antigen-Specific Immunotherapies for the Treatment of Autoimmune Disorders

Autoimmune disorders are a challenging problem for both afflicted patients and pharmaceutical scientists, since they involve one of the most complex biological systems – the immune system. A dysregulation of antigen recognition is at the center of autoimmune disorders, and can occur in a variety of host tissues throughout the body. Further complicating these diseases is the high degree of variability in terms of clinical manifestation. Traditional therapies for autoimmune disorders, such as corticosteroids or immunomodulators, generally focus on symptom suppression or slowing disease progression rather than treating the underlying cause, which is rarely fully understood. New approaches to treatments in which a disease-causing autoantigen is known seek to leverage antigen specificity through the development of antigen-specific immunotherapies (ASIT). In this research, we explore different novel approaches to ASIT focused on chemical conjugation, including the design and development of a new therapeutic class, antigen-drug conjugates (AgDCs). By reversing the paradigm of antibody-drug conjugates (ADCs), AgDCs exploit the directing effect of the autoantigen towards diseased cell populations, coupled with the immunomodulatory effects of a small molecule drug. Soluble Antigen Arrays (SAgAs) focus on disrupting immune recognition at the immunological synapse by conjugating autoantigen on a multivalent polymer support. Polymer-drug conjugates also present a unique opportunity as a depot delivery system with the potential for targeted applications. The strategies presented here carry an overarching goal to increase therapeutic specificity while limiting off-target effects, in an attempt to develop improved treatments with better efficacy and safety profiles for patients

Sex Differences in Adult Cognitive Deficits after Adolescent Nicotine Exposure in Rats

This study was designed to determine whether deficits in adult serial pattern learning caused by adolescent nicotine exposure persist as impairments in asymptotic performance, whether adolescent nicotine exposure differentially retards learning about pattern elements that are inconsistent with “perfect” pattern structure, and whether there are sex differences in rats’ response to adolescent nicotine exposure as assessed by a serial multiple choice task. The current study replicated the results of our initial report (Fountain, Rowan, Kelley, Willey, & Nolley, 2008) using this task by showing that adolescent nicotine exposure (1.0 mg/kg/day nicotine for 35 days) produced a specific cognitive impairment in male rats that persisted into adulthood at least a month after adolescent nicotine exposure ended. In addition, sex differences were observed even in controls, with additional evidence that adolescent nicotine exposure significantly impaired learning relative to same-sex controls for chunk boundary elements in males and for violation elements in females. All nicotine-induced impairments were overcome by additional training so that groups did not differ at asymptote. An examination of the types of errors rats made indicated that adolescent nicotine exposure slowed learning without affecting rats’ cognitive strategy in the task. This data pattern suggests that exposure to nicotine in adolescence may have impaired different aspects of adult stimulus-response discrimination learning processes in males and females, but left abstract rule learning processes relatively spared in both sexes. These effects converge with other findings in the field and reinforce the concern that adolescent nicotine exposure poses an important threat to cognitive capacity in adulthood

Role of soil texture, clay mineralogy, location, and temperature in coarse wood decomposition—a mesocosm experiment

Of all the major pools of terrestrial carbon (C), the dynamics of coarse woody debris (CWD) are the least understood. In contrast to soils and living vegetation, the study of CWD has rarely relied on ex situ methods for elaborating controls on decomposition rates. In this study, we report on a mesocosm incubation experiment examining how clay amount (8%, 16%, and 24% clay), clay type (soil reconstructed with kaolinite vs. montmorillonite), wood placement (on litter layer surface, at the litter layer–soil interface, buried in the mineral soil), and laboratory incubation temperature (10°, 20°, or 30°C) control decomposition rates of highly standardized stakes and blocks of coarse aspen wood. Clay type effect was pronounced, with wood decomposing more quickly in kaolinite- than in montmorillonite-amended soils, perhaps due to a combined effect of moisture and microbial access to the substrate. Clay amount had only very limited effect on wood decomposition, which was a function of contact with the mineral soil (Surface \u3c Interface \u3c Mineral), perhaps due to greater contact with the decomposer community. Temperature effects were significant and dependent on interactions with clay type and wood placement. Effects of temperature on wood decomposition declined as the effects of soil variables increased, suggesting a hierarchy of controls on wood decomposition rates. Both water content and temperature had a strong effect on wood decomposition. Our results highlight that multiple interacting factors likely regulate wood decomposition processes. Multifactorial field experiments are needed to examine the physical, chemical, and biological factors controlling wood decompositio

Immunogenicity and efficacy of alphavirus-derived replicon vaccines for respiratory syncytial virus and human metapneumovirus in nonhuman primates

Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are major causes of illness among children, the elderly, and the immunocompromised. No vaccine has been licensed for protection against either of these viruses. We tested the ability of two Venezuelan equine encephalitis virus-based viral replicon particle (VEE-VRP) vaccines that express the hRSV or hMPV fusion (F) protein to confer protection against hRSV or hMPV in African green monkeys. Animals immunized with VEE-VRP vaccines developed RSV or MPV F-specific antibodies and serum neutralizing activity. Compared to control animals, immunized animals were better able to control viral load in the respiratory mucosa following challenge and had lower levels of viral genome in nasopharyngeal and bronchoalveolar lavage fluids. The high level of immunogenicity and protective efficacy induced by these vaccine candidates in nonhuman primates suggest that they hold promise for further development

Concurrent Performances: Reinforcement By Different Doses Of Intravenous Cocaine In Rhesus Monkeys 1

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96683/1/jeab.1974.22-179.pd

Food- and drug-reinforced responding: Effects of DITA and d -amphetamine

Intravenous pretreatment with DITA (0.1–1.0 mg/kg) decreased the rate of food-reinforced lever pressing in rhesus monkeys. Response rate decreases were dose-dependent but showed the development of tolerance. Self-administration of DITA was initiated and maintained in each of three monkeys when 30 lever presses were required to produce each injection. Maximal response rate during periods of drug availability was maintained by 0.03 mg/kg/injection while higher and lower doses (0.01 and 0.10 mg/kg/injection) maintained lower response rates. Response rate in periods of food availability immediately preceding drug periods was relatively constant across sessions; response rate in periods of food availability immediately following drug periods, however, decreased with increasing amounts of drug self-administered. Replication of initial self-administration doses produced results comparable to original determinations in contrast to the tolerance observed with DITA effects upon food-reinforced responding. DITA was about 3 times less potent than d -amphetamine in maintaining response rates in drug periods and in decreasing the rate of subsequent food-reinforced responding.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46391/1/213_2004_Article_BF00437608.pd

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin