Expert system for on-board satellite scheduling and control

An Expert System is described which Rockwell Satellite and Space Electronics Division (S&SED) is developing to dynamically schedule the allocation of on-board satellite resources and activities. This expert system is the Satellite Controller. The resources to be scheduled include power, propellant and recording tape. The activities controlled include scheduling satellite functions such as sensor checkout and operation. The scheduling of these resources and activities is presently a labor intensive and time consuming ground operations task. Developing a schedule requires extensive knowledge of the system and subsystems operations, operational constraints, and satellite design and configuration. This scheduling process requires highly trained experts anywhere from several hours to several weeks to accomplish. The process is done through brute force, that is examining cryptic mnemonic data off line to interpret the health and status of the satellite. Then schedules are formulated either as the result of practical operator experience or heuristics - that is rules of thumb. Orbital operations must become more productive in the future to reduce life cycle costs and decrease dependence on ground control. This reduction is required to increase autonomy and survivability of future systems. The design of future satellites require that the scheduling function be transferred from ground to on board systems

Dupilumab for bullous pemphigoid with intractable pruritus

Bullous pemphigoid (BP) is an autoimmune blistering disorder that predominantly affects the elderly. Treatment regimens typically include topical and systemic immunosuppressive medications. Although effective, systemic corticosteroids are sometimes poorly tolerated in the elderly patient, contributing to the overall morbidity and mortality of BP. Dupilumab is a monoclonal antibody targeting interleukin 4 receptor alpha (IL4R?), approved for the treatment of atopic dermatitis, as well as moderate to severe asthma and chronic rhinosinusitis with nasal polyposis. In recent reports, dupilumab has been successfully used off-label to treat a variety of pruritic disorders, including chronic spontaneous urticaria [1], anal and genital itch [2], allergic contact dermatitis [3], and prurigo nodularis [4, 5]. We report here a case of an elderly patient with refractory BP whose symptoms of pruritus and blistering became well-controlled with the addition of dupilumab to the treatment regimen

Complement protein levels in plasma astrocyte-derived exosomes are abnormal in conversion from mild cognitive impairment to Alzheimer's disease dementia.

IntroductionLevels of complement proteins (CPs) in plasma astrocyte-derived exosomes (ADEs) that are abnormal in Alzheimer's disease (AD) have not been assessed in mild cognitive impairment (MCI).MethodsParticipants (n = 20 per group) had either MCI converting to dementia within 3 years (MCIC), MCI remaining stable over 3 years (MCIS), Alzheimer's disease, or were controls. CPs of ADEs isolated from plasmas by anti-human glutamine aspartate transporter antibody absorption were quantified by ELISAs.ResultsADE levels of C1q and C4b of the classical pathway, factor D and fragment Bb of the alternative pathway, and C5b, C3b, and C5b-C9 of both pathways were significantly higher in patients with MCIC than those with MCIS. ADE levels of inhibitory CPs decay-accelerating factor, CD46, CD59, and type 1 complement receptor were significantly lower in patients with MCIC than those with MCIS.DiscussionADE CPs are components of neurotoxic neuroinflammation that may be predictive biomarkers of MCI conversion to Alzheimer's disease

Policy Audit: Social Protection Policies and Urban Poor LBTs in the Philippines

LGBT discourses worldwide have tended to focus on marriage equality at the expense of other equally pressing but sometimes ‘less sexy’ concerns such as gender-based discrimination and violence, and poverty among sexual minorities. GALANG’s work with lesbians, bisexual women, and trans men (LBTs) living in urban slums indicates that while marriage is of course an important issue, it is hardly foremost in the minds of many Filipino LBTs who are systematically deprived of decent jobs, humane housing conditions, and adequate health care. Today, although Philippine law does not criminalise consensual same-sex acts and the principles of equality and non-discrimination are enshrined in the Constitution, homosexuality is policed by various social institutions, including the nuclear family and the Roman Catholic Church, which often eschew any sexual behaviour that takes place outside the context of marriage and family life. This policy audit seeks to: (1) identify and analyse the sexuality content of the selected social protection policies; (2) voice the concerns and experiences of LBTs living in GALANG’s partner urban poor communities in Quezon City; (3) share and communicate the findings of this audit with an eye towards influencing the conduct of donors and national and sub-national decision-makers, including mainstream activist organisations focusing on sexuality, social justice and feminism; (4) draw cross-cutting policy lessons that can inform future advocacy and policy development; and (5) stimulate others to replicate this analysis in their own settings.DFI

Bridging the Expertise of Advocates and Academics to Identify Reproductive Justice Learning Outcomes

Phenomenon: Reproductive justice (RJ) is defined by women of color advocates as the right to have children, not have children and parent children while maintaining reproductive autonomy. In the United States, physicians have been complicit in multiple historical reproductive injustices, involving coercive sterilization of thousands of people of color, low income, and disabilities. Currently, reproductive injustices continue to occur; however, physicians have no formal RJ medical education to address injustices. The objective of this study was to engage leading advocates within the movement using a Delphi method to identify critical components for such a curriculum. Approach: In 2016, we invited 65 RJ advocates and leaders to participate in an expert panel to design RJ medical education. A 3-round Delphi survey was distributed electronically to identify content for inclusion in an RJ curriculum. In the next 2 survey rounds, experts offered feedback and revisions and rated agreement with including content recommendations in the final curriculum. We calculated descriptive statistics to analyze quantitative data. A team with educational expertise wrote learning outcomes based on expert content recommendations. Findings: Of the 65 RJ advocates and leaders invited, 41 participated on the expert panel of the Delphi survey. In the first survey, the expert panel recommended 58 RJ content areas through open-ended response. Over the next 2 rounds, there was consensus among the panel to include 52 of 58 of these areas in the curriculum. Recommended content fell into 11 broad domains: access, disparities, and structural competency; advocacy; approaches to reproductive healthcare; contemporary law and policy; cultural safety; historical injustices; lesbian, gay, bisexual, transgender, queer/questioning, and intersex health; oppression, power, and bias training; patient care; reproductive health; and RJ definitions. The 97 learning outcomes created from this process represented both unique and existing educational elements. Insights: A collaborative methodology infused with RJ values can bridge experts in advocacy and academics. New learning outcomes identified through this process can enhance medical education; however, it is just as important to consider education in RJ approaches to care as it is knowledge about that care. We must explore the pedagogic process of RJ medical education while considering that expertise in this area may exist outside of the medical community and thus there is a need to partner with RJ advocates. Finally, we expect to use innovative teaching methods to transform medical education and achieve an RJ focus

Assessing Neuronal and Astrocyte Derived Exosomes From Individuals With Mild Traumatic Brain Injury for Markers of Neurodegeneration and Cytotoxic Activity.

Mild traumatic brain injury (mTBI) disproportionately affects military service members and is very difficult to diagnose. To-date, there is currently no blood-based, diagnostic biomarker for mTBI cases with persistent post concussive symptoms. To examine the potential of neuronally-derived (NDE) and astrocytic-derived (ADE) exosome cargo proteins as biomarkers of chronic mTBI in younger adults, we examined plasma exosomes from a prospective longitudinal study of combat-related risk and resilience, marine resiliency study II (MRSII). After return from a combat-deployment participants were interviewed to assess TBI exposure while on deployment. Plasma exosomes from military service members with mTBI (mean age, 21.7 years, n = 19, avg. days since injury 151), and age-matched, controls (deployed service members who did not endorse a deployment-related TBI or a pre-deployment history of TBI; mean age, 21.95 years, n = 20) were precipitated and enriched against a neuronal adhesion protein, L1-CAM, and an astrocyte marker, glutamine aspartate transporter (GLAST) using magnetic beads to immunocapture the proteins and subsequently selected by fluorescent activated cell sorting (FACS). Extracted protein cargo from NDE and ADE preparations were quantified for protein levels implicated in TBI neuropathology by standard ELISAs and on the ultra-sensitive single molecule assay (Simoa) platform. Plasma NDE and ADE levels of Aβ42 were significantly higher while plasma NDE and ADE levels of the postsynaptic protein, neurogranin (NRGN) were significantly lower in participants endorsing mTBI exposure compared to controls with no TBI history. Plasma NDE and ADE levels of Aβ40, total tau, and neurofilament light (NFL), P-T181-tau, P-S396-tau were either undetectable or not significantly different between the two groups. In an effort to understand the pathogenetic potential of NDE and ADE cargo proteins, neuron-like cultures were treated with NDE and ADE preparations from TBI and non-TBI groups. Lastly, we determined that plasma NDE but not ADE cargo proteins from mTBI samples were found to be toxic to neuron-like recipient cells in vitro. These data support the presence of markers of neurodegeneration in NDEs of mTBI and suggest that these NDEs can be used as tools to identify pathogenic mechanisms of TBI

The Roles of Individual Mammalian Argonautes in RNA Interference In Vivo

Argonaute 2 (Ago2) is the only mammalian Ago protein capable of mRNA cleavage. It has been reported that the activity of the short interfering RNA targeting coding sequence (CDS), but not 3′ untranslated region (3′UTR) of an mRNA, is solely dependent on Ago2 in vitro. These studies utilized extremely high doses of siRNAs and overexpressed Ago proteins, as well as were directed at various highly expressed reporter transgenes. Here we report the effect of Ago2 in vivo on targeted knockdown of several endogenous genes by siRNAs, targeting both CDS and 3′UTR. We show that siRNAs targeting CDS lose their activity in the absence of Ago2, whereas both Ago1 and Ago3 proteins contribute to residual 3′UTR-targeted siRNA-mediated knockdown observed in the absence of Ago2 in mouse liver. Our results provide mechanistic insight into two components mediating RNAi under physiological conditions: mRNA cleavage dependent and independent. In addition our results contribute a novel consideration for designing most efficacious siRNA molecules with the preference given to 3′UTR targeting as to harness the activity of several Ago proteins.Alnylam Pharmaceuticals (Firm

Relationships between physiological characteristics and trace metal body burdens of banded garden spiders Argiope trifasciata (Araneae, Araneidae)

Banded garden spiders (Argiope trifasciata) were collected at the Ballona Wetlands, a metal contaminated salt marsh. The relationship between spider body size and individual metal loads was investigated. Biochemical markers were identified in spider fecal material and found to correlate to body metal levels. Body metal dry weight concentrations of Cd, Cr, Cu, Zn and total metals in female A. trifasciata exhibited distinct patterns of spatial and annual variation during 2006 and 2007. Spider body size was homogeneous across sites in both years, while increased Cd and Cr concentrations were sometimes associated with a reduction in spider size, though the influence of Cr was quite minor. Spiders with higher body Cu levels showed a reduction in peak area for hypoxanthine and an un-identified component in fecal material chromatograms. Spatial and annual differences in metal bioaccumulation are likely mediated by variation in site-specific environmental parameters and rainfall, while the negative relationships between body size and metal levels are presumably a consequence of a spider\u27s expenditure of energy for metal tolerance mechanisms vs. foraging and growth. Finally, correlating body metal levels with excreta products constitutes a novel method to non-invasively predict metal levels in spiders

In vivo silencing of alpha-synuclein using naked siRNA

<p>Abstract</p> <p>Background</p> <p>Overexpression of α-synuclein (SNCA) in families with multiplication mutations causes parkinsonism and subsequent dementia, characterized by diffuse Lewy Body disease <it>post-mortem</it>. Genetic variability in <it>SNCA </it>contributes to risk of idiopathic Parkinson's disease (PD), possibly as a result of overexpression. <it>SNCA </it>downregulation is therefore a valid therapeutic target for PD.</p> <p>Results</p> <p>We have identified human and murine-specific siRNA molecules which reduce <it>SNCA in vitro</it>. As a proof of concept, we demonstrate that direct infusion of chemically modified (naked), murine-specific siRNA into the hippocampus significantly reduces <it>SNCA </it>levels. Reduction of <it>SNCA </it>in the hippocampus and cortex persists for a minimum of 1 week post-infusion with recovery nearing control levels by 3 weeks post-infusion.</p> <p>Conclusion</p> <p>We have developed naked gene-specific siRNAs that silence expression of <it>SNCA in vivo</it>. This approach may prove beneficial toward our understanding of the endogenous functional equilibrium of <it>SNCA</it>, its role in disease, and eventually as a therapeutic strategy for α-synucleinopathies resulting from <it>SNCA </it>overexpression.</p