Cultural analysis case study : implementaiton of acquisition reform within the Department of Defense

Thesis (M.S.)--Massachusetts Institute of Technology, Sloan School of Management, 1997.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Includes bibliographical references (leaves 102-103).by Donna R. Doane.M.S

A Sensitive Membrane-Targeted Biosensor for Monitoring Changes in Intracellular Chloride in Neuronal Processes

Background: Regulation of chloride gradients is a major mechanism by which excitability is regulated in neurons. Disruption of these gradients is implicated in various diseases, including cystic fibrosis, neuropathic pain and epilepsy. Relatively few studies have addressed chloride regulation in neuronal processes because probes capable of detecting changes in small compartments over a physiological range are limited. Methodology/Principal Findings: In this study, a palmitoylation sequence was added to a variant of the yellow fluorescent protein previously described as a sensitive chloride indicator (YFPQS) to target the protein to the plasma membrane (mbYFPQS) of cultured midbrain neurons. The reporter partitions to the cytoplasmic face of the cellular membranes, including the plasma membrane throughout the neurons and fluorescence is stable over 30-40 min of repeated excitation showing less than 10% decrease in mbYFPQS fluorescence compared to baseline. The mbYFPQS has similar chloride sensitivity (k 50 = 41 mM) but has a shifted pKa compared to the unpalmitoylated YFPQS variant (cytYFPQS) that remains in the cytoplasm when expressed in midbrain neurons. Changes in mbYFPQS fluorescence were induced by the GABA A agonist muscimol and were similar in the soma and processes of the midbrain neurons. Amphetamine also increased mbYFPQS fluorescence in a subpopulation of cultured midbrain neurons that was reversed by the selective dopamine transporter (DAT) inhibitor, GBR12909, indicating that mbYFPQS is sensitive enough to detect endogenous DAT activity in midbrain dopamine (DA) neurons. Conclusions/Significance: The mbYFPQS biosensor is a sensitive tool to study modulation of intracellular chloride levels in neuronal processes and is particularly advantageous for simultaneous whole-cell patch clamp and live-cell imaging experiments. © 2012 Watts et al

New Horizons: Long-Range Kuiper Belt Targets Observed by the Hubble Space Telescope

We report on Hubble Space Telescope (HST) observations of three Kuiper Belt Objects (KBOs), discovered in our dedicated ground-based search campaign, that are candidates for long-range observations from the New Horizons spacecraft: 2011 JY31, 2011 HZ102, and 2013 LU35. Astrometry with HST enables both current and future critical accuracy improvements for orbit precision, required for possible New Horizons observations, beyond what can be obtained from the ground. Photometric colors of all three objects are red, typical of the Cold Classical dynamical population within which they reside; they are also the faintest KBOs to have had their colors measured. None are observed to be binary with HST above separations of ~0.02 arcsec (~700 km at 44 AU) and {\Delta}m less than or equal to 0.5.Comment: Pages: 11, Figures: 2, Tables: 3, Icarus, available online May 2014 (http://dx.doi.org/10.1016/j.icarus.2014.04.014

Amphetamine Modulates Excitatory Neurotransmission through Endocytosis of the Glutamate Transporter EAAT3 in Dopamine Neurons

SummaryAmphetamines modify the brain and alter behavior through mechanisms generally attributed to their ability to regulate extracellular dopamine concentrations. However, the actions of amphetamine are also linked to adaptations in glutamatergic signaling. We report here that when amphetamine enters dopamine neurons through the dopamine transporter, it stimulates endocytosis of an excitatory amino acid transporter, EAAT3, in dopamine neurons. Consistent with this decrease in surface EAAT3, amphetamine potentiates excitatory synaptic responses in dopamine neurons. We also show that the process of internalization is dynamin- and Rho-mediated and requires a unique sequence in the cytosolic C terminus of EAAT3. Introduction of a peptide based on this motif into dopamine neurons blocks the effects of amphetamine on EAAT3 internalization and its action on excitatory responses. These data indicate that the internalization of EAAT3 triggered by amphetamine increases glutamatergic signaling and thus contributes to the effects of amphetamine on neurotransmission

Early-life adversity programs long-term cytokine and microglia expression within the HPA axis in female Japanese quail

This work was funded by the Biotechnology and Biological Sciences Research Council (BBSRC grant no. BB/L002264/1 to K.A.S., C.Z. and S.D.H.), a David Phillips Research Fellowship (K.A.S.) and an EASTBIO BBSRC Doctoral Training Programme studentship (grant no. BB/J01446X/1 to D.J.W., supervisors K.A.S., S.D.H.). Data are available from Mendeley (Walker, 2019): http://dx.doi.org/10.17632/ 6r7d2pg2zk.1Stress exposure during prenatal and postnatal development can have persistent and often dysfunctional effects on several physiological systems, including immune function, affecting the ability to combat infection. The neuroimmune response is inextricably linked to the action of the hypothalamic–pituitary–adrenal (HPA) axis. Cytokines released from neuroimmune cells, including microglia, activate the HPA axis, while glucocorticoids in turn regulate cytokine release from microglia. Because of the close links between these two physiological systems, coupled with potential for persistent changes to HPA axis activity following developmental stress, components of the neuroimmune system could be targets for developmental programming. However, little is known of any programming effects of developmental stress on neuroimmune function. We investigated whether developmental stress exposure via elevated prenatal corticosterone (CORT) or postnatal unpredictable food availability had long-term effects on pro- (IL-1β) and anti-inflammatory (IL-10) cytokine and microglia-dependent gene (CSF1R) expression within HPA axis tissues in a precocial bird, the Japanese quail (Coturnix japonica). Following postnatal stress, we observed increased IL-1β expression in the pituitary gland, reduced IL-10 expression in the amygdala and hypothalamus, and reduced CSF1R expression within the hypothalamus and pituitary gland. Postnatal stress disrupted the ratio of IL-1β:IL-10 expression within the hippocampus and hypothalamus. Prenatal stress only increased IL-1β expression in the pituitary gland. We found no evidence for interactive or cumulative effects across life stages on basal cytokine and glia expression in adulthood. We show that postnatal stress may have a larger impact than elevated prenatal CORT on basal immunity in HPA-axis-specific brain regions, with changes in cytokine homeostasis and microglia abundance. These results provide evidence for postnatal programming of a pro-inflammatory neuroimmune phenotype at the expense of reduced microglia, which could have implications for central nervous system health and subsequent neuroimmune responses.Publisher PDFPeer reviewe

Newcomer families' experiences with programs and services to support early childhood development in Canada: A scoping review

It can be difficult for families with young children to navigate early childhood development supports. In particular, newcomer families often encounter additional barriers and require resources, programs, and services that are tailored to their unique assets, experiences, and needs. We conducted a scoping review of the literature published between 2000 and 2019 to explore what is known about newcomer families’ experiences with programs and services to support early childhood development in Canada. We searched 12 databases, screened 2390 articles, and included 34 articles for synthesis and analysis. Three common and connected themes were identified: 1) effective intercultural understanding, responsiveness, and communication are critical to ensuring full access to meaningful programs and services; 2) some newcomer families face systemic barriers exacerbated by their immigration status, and; 3) feelings and perceptions of families and service providers, as well as social supports, networks, and relationships influence how programs and services are accessed and experienced. Our review identifies the requirement for additional, participatory research that centres the voices and perspectives of newcomer children and their families and the need to expand that research to less populated and rural areas of the country to inform meaningful and culturally relevant policies, programs, and services for newcomer families to support their children’s well-being

Brain differences between persistent and remitted attention deficit hyperactivity disorder

Previous resting state studies examining the brain basis of attention deficit hyperactivity disorder have not distinguished between patients who persist versus those who remit from the diagnosis as adults. To characterize the neurobiological differences and similarities of persistence and remittance, we performed resting state functional magnetic resonance imaging in individuals who had been longitudinally and uniformly characterized as having or not having attention deficit hyperactivity disorder in childhood and again in adulthood (16 years after baseline assessment). Intrinsic functional brain organization was measured in patients who had a persistent diagnosis in childhood and adulthood (n = 13), in patients who met diagnosis in childhood but not in adulthood (n = 22), and in control participants who never had attention deficit hyperactivity disorder (n = 17). A positive functional correlation between posterior cingulate and medial prefrontal cortices, major components of the default-mode network, was reduced only in patients whose diagnosis persisted into adulthood. A negative functional correlation between medial and dorsolateral prefrontal cortices was reduced in both persistent and remitted patients. The neurobiological dissociation between the persistence and remittance of attention deficit hyperactivity disorder may provide a framework for the relation between the clinical diagnosis, which indicates the need for treatment, and additional deficits that are common, such as executive dysfunctions.McGovern Institute for Brain Research at MIT (Poitras Center for Affective Disorders Research)Massachusetts General Hospital (Paediatric Psychopharmacology Council Fund

Photometry of Kuiper belt object (486958) Arrokoth from New Horizons LORRI

On January 1st 2019, the New Horizons spacecraft flew by the classical Kuiper belt object (486958) Arrokoth (provisionally designated 2014 MU69), possibly the most primitive object ever explored by a spacecraft. The I/F of Arrokoth is analyzed and fit with a photometric function that is a linear combination of the Lommel-Seeliger (lunar) and Lambert photometric functions. Arrokoth has a geometric albedo of p_v = 0.21_(−0.04)^(+0.05) at a wavelength of 550 nm and ≈0.24 at 610 nm. Arrokoth's geometric albedo is greater than the median but consistent with a distribution of cold classical Kuiper belt objects whose geometric albedos were determined by fitting a thermal model to radiometric observations. Thus, Arrokoth's geometric albedo adds to the orbital and spectral evidence that it is a cold classical Kuiper belt object. Maps of the normal reflectance and hemispherical albedo of Arrokoth are presented. The normal reflectance of Arrokoth's surface varies with location, ranging from ≈0.10–0.40 at 610 nm with an approximately Gaussian distribution. Both Arrokoth's extrema dark and extrema bright surfaces are correlated to topographic depressions. Arrokoth has a bilobate shape and the two lobes have similar normal reflectance distributions: both are approximately Gaussian, peak at ≈0.25 at 610 nm, and range from ≈0.10–0.40, which is consistent with co-formation and co-evolution of the two lobes. The hemispherical albedo of Arrokoth varies substantially with both incidence angle and location, the average hemispherical albedo at 610 nm is 0.063 ± 0.015. The Bond albedo of Arrokoth at 610 nm is 0.062 ± 0.015