705 research outputs found
Analytical comparison of transient and steady state visual evoked cortical potentials
To better describe the linear-dynamic properties of the human visual-cortical response system, transient and steady state Visual Evoked Response Potentials (VERP) were observed. The stimulus presentation device provided both the evoking stimulus (flickering or pulsing lights) and a video task display. The steady state stimulus was modulated by a complex, ten frequency, sum-of-sines, wave. The transient VERP was the time-locked average of the EEG to a series of narrow light pulses (pulse width of 10 msec). The Fourier transform of the averaged pulses had properties that approximate band limited white noise, i.e., a flat spectrum over the frequency region spanned by the 10 summed sines. The Fourier transform of both the steady state and the transient evoked potentials resulted in transfer that are equivalent and therefore comparable. To investigate the effects of task loading on evoked potentials, a grammatical reasoning task was provided. Results support the relevancy of continued application of a systems engineering approach for describing neurosensory functioning
Packaging, deployment, and panel design concepts for a truss-stiffened 7-panel precision deployable reflector with feed boom
A concept is presented for achieving a remotely deployable truss-stiffened reflector consisting of seven integrated sandwich panels that form the reflective surface, and an integrated feed boom. The concept has potential for meeting aperture size and surface precision requirements for some high-frequency microwave remote sensing applications. The packaged reflector/feed boom configuration is a self-contained unit that can be conveniently attached to a spacecraft bus. The package has a cylindrical envelope compatible with typical launch vehicle shrouds. Dynamic behavior of a deployed configuration having a 216-inch focal length and consisting of 80-inch-diameter, two-inch-thick panels is examined through finite-element analysis. Results show that the feed boom and spacecraft bus can have a large impact on the fundamental frequency of the deployed configuration. Two candidate rib-stiffened sandwich panel configurations for this application are described, and analytical results for panel mass and stiffness are presented. Results show that the addition of only a few rib stiffeners, if sufficiently deep, can efficiently improve sandwich panel stiffness
Parenting the Premature Infant: Potential Iatrogenesis from the Neonatal Intensive Care Experience
(1) Developmental outcomes of premature infants are associated with the quality of the home environment and the level of parenting skills the family possesses. Successful development of the parenting role may be negatively influenced by the Neonatal Intensive Care Unit (NICU) environment and nursing practices. Identification of interventions that promote the development of parenting skills in the NICU can potentially improve developmental outcomes for premature infants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73814/1/j.1524-475X.1996.00046.x.pd
Simultaneous targeted exchange of two nucleotides by single-stranded oligonucleotides clusters within a region of about fourteen nucleotides
Sex differences in the effect of chronic delivery of the buprenorphine analogue BU08028 on heroin relapse and choice in a rat model of opioid maintenance
Background and Purpose: Maintenance treatment with opioid agonists (buprenorphine, methadone) decreases opioid use and relapse. We recently modelled maintenance treatment in rats and found that chronic delivery of buprenorphine or the μ opioid receptor partial agonist TRV130 decreased relapse to oxycodone seeking and taking. Here, we tested the buprenorphine analogue BU08028 on different heroin relapse-related measures and heroin versus food choice. Experimental Approach: For relapse assessment, we trained male and female rats to self-administer heroin (6 h·day−1, 14 days) in Context A and then implanted osmotic minipumps containing BU08028 (0, 0.03 or 0.1 mg·kg−1·d−1). Effects of chronic BU08028 delivery were tested on (1) incubation of heroin-seeking in a non-drug Context B, (2) extinction responding reinforced by heroin-associated discrete cues in Context B, (3) reinstatement of heroin-seeking induced by re-exposure to Context A and (4) re-acquisition of heroin self-administration in Context A. For choice assessment, we tested the effect of chronic BU08028 delivery on heroin versus food choice. Key Results: Chronic BU08028 delivery decreased incubation of heroin seeking. Unexpectedly, BU08028 increased re-acquisition of heroin self-administration selectively in females. Chronic BU08028 had minimal effects on context-induced reinstatement and heroin versus food choice in both sexes. Finally, exploratory post hoc analyses suggest that BU08028 decreased extinction responding selectively in males. Conclusions and Implications: Chronic BU08028 delivery had both beneficial and detrimental, sex-dependent, effects on different triggers of heroin relapse and minimal effects on heroin choice in both sexes. Results suggest that BU08028 would not be an effective opioid maintenance treatment in humans.</p
Proteomic Analysis Identifies NDUFS1 and ATP5O as Novel Markers for Survival Outcome in Prostate Cancer
Simple Summary Due to the heterogeneity of prostate cancer (PCa), it is still difficult to provide risk stratification. Metabolic changes in PCa tissue have been described during tumor progression at genetic and transcriptomic level, but these have not yet clearly contributed to improved diagnosis and therapy. The aim of our study was to identify novel markers for aggressive prostate cancer in a proteomics-derived dataset by immunohistochemical analysis and correlation with transcriptomic data. Here, we provide potential new markers-NDUFS1 and ATP5O-for risk stratification in PCa. Additionally, we reveal for the first time a concordant increase of NDUFS1/ATP5O of mRNA expression in transcriptomic datasets and at protein level. We aimed to identify novel markers for aggressive prostate cancer in a STAT3-low proteomics-derived dataset of mitochondrial proteins by immunohistochemical analysis and correlation with transcriptomic data and biochemical recurrence in a STAT3 independent PCa cohort. Formalin-fixed paraffin-embedded tissue (FFPE) sample selection for proteomic analysis and tissue-microarray (TMA) generation was conducted from a cohort of PCa patients. Retrospective data analysis was performed with the same cohort. 153 proteins differentially expressed between STAT3-low and STAT3-high samples were identified. Out of these, 46 proteins were associated with mitochondrial processes including oxidative phosphorylation (OXPHOS), and 45 proteins were upregulated, including NDUFS1/ATP5O. In a STAT3 independent PCa cohort, high expression of NDUFS1/ATP5O was confirmed by immunocytochemistry (IHC) and was significantly associated with earlier biochemical recurrence (BCR). mRNA expression levels for these two genes were significantly higher in intra-epithelial neoplasia and in PCa compared to benign prostate glands. NDUFS1/ATP5O levels are increased both at the mRNA and protein level in aggressive PCa. Our results provide evidence that NDUFS1/ATP5O could be used to identify high-risk PCa patients
Serotonin 5-HT2A receptors underlie increased motor behaviors induced in dopamine-depleted rats by intrastriatal 5-HT2A/2C agonism
ABSTRACT Gene expression studies have suggested that dopamine (DA) depletion increases the sensitivity of striatal direct pathway neurons to the effects of serotonin (5-HT) via the 5-HT 2 receptor. The present study examined the possible influence(s) of 5-HT 2A or 5-HT 2C receptor-mediated signaling locally within the striatum on motor behavior triggered by 5-HT 2 receptor agonism in the neonatal DA-depleted rat. Male Sprague-Dawley rats were treated with 6-hydroxydopamine (6-OHDA; 60 g in 5 l per lateral ventricle) on postnatal day 3 to achieve near-total DA depletion bilaterally. Sixty days later, sham-operated (saline-injected) or 6-OHDA-treated rats were challenged with the 5-HT 2A/2C agonist DOI [(Ï®)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane] or saline either by systemic treatment or bilateral intrastriatal infusion. Motor behavior was quantified for 60 min after agonist injection using computerized activity monitors. Systemic DOI treatment (0.2 or 2.0 mg/kg i.p.) was more effective in inducing motor activity in the DA-depleted group compared with intact controls. Intrastriatal DOI infusion (1.0 or 10.0 g/side) also produced a significant rise in motor activity in the DA-depleted group during the 30-to 60-min period of behavioral analysis but did not influence behavior in intact animals. The effects of intrastriatal DOI infusion were blocked by intrastriatal coinfusion of the 5-HT 2 antagonist ketanserin (1. A loss of dopamine (DA) transmission to the rodent striatum during early postnatal development results in a compensatory increase in serotonin (5-HT) innervation to the dorsal striatum Several studies indicate that 5-HT 2A receptors are positioned to mediate the influences of enhanced 5-HT signaling in the DA-depleted striatum. First, 5-HT release agents and 5-HT 2 receptor agonists gain potency in inducing striatal preprotachykinin (PPT; encodes substance P and neurokini
Kindlin-3 maintains marginal zone B cells but confines follicular B cell activation and differentiation
Integrin-mediated interactions between hematopoietic cells and their microenvironment are important for the development and function of immune cells. Here, the role of the integrin adaptor Kindlin-3 in B cell homeostasis is studied. Comparing the individual steps of B cell development in B cell-specific Kindlin-3 or alpha4 integrin knockout mice, we found in both conditions a phenotype of reduced late immature, mature, and recirculating B cells in the bone marrow. In the spleen, constitutive B cell-specific Kindlin-3 knockout caused a loss of marginal zone B cells and an unexpected expansion of follicular B cells. Alpha4 integrin deficiency did not induce this phenotype. In Kindlin-3 knockout B cells VLA-4 as well as LFA-1-mediated adhesion was abrogated, and short-term homing of these cells in vivo was redirected to the spleen. Upon inducible Kindlin-3 knockout, marginal zone B cells were lost due to defective retention within 2 weeks, while follicular B cell numbers were unaltered. Kindlin-3 deficient follicular B cells displayed higher IgD, CD40, CD44, CXCR5, and EBI2 levels, and elevated PI3K signaling upon CXCR5 stimulation. They also showed transcriptional signatures of spontaneous follicular B cell activation. This activation manifested in scattered germinal centers in situ, early plasmablasts differentiation, and signs of IgG class switch
- …