Precision slew/settle technologies for flexible spacecraft

Many spacecraft missions in the next decade will require both a high degree of agility and precision pointing. Agility includes both rotational maneuvering for retargeting and translational motion for orbit adjustment and threat avoidance. The major challenge associated with such missions is the need for control over a wide range of amplitudes and frequencies, ranging from tens of degrees at less than 1 Hz to a few micron radians at hundreds of Hz. TRW's internally funded Precision Control of Agile Spacecraft (PCAS) project is concerned with developing and validating in hardware the tools necessary to successfully complete the combined agile maneuvering/precision pointing missions. Development has been undertaken on a number of fronts for quietly slewing flexible structures. Various methods for designing slew torque profiles have been investigated. Prime candidates for slew/settle scenarios include Inverse Dynamics and Parameterized Function Space. Joint work with Processor Bayo at the University of California, Santa Barbara and Professor Flashner at the University of Southern California has led to promising torque profile design methods. Active and passive vibration suppression techniques also play a key role for rapid slew/settle mission scenarios. Active members with local control loops and passive members with high loss factor viscoelastic material have been selected for hardware verification. Progress in each of these areas produces large gains in the quiet slewing of flexible spacecraft. The main thrust of the effort to date has been the development of a modular testbed for hardware validation of the precision control concepts. The testbed is a slewing eighteen foot long flexible truss. Active and passive members can be interchanged with the baseline aluminum members to augment the inherent damping in the system. For precision control the active members utilize control laws running on a high speed digital structural control processor. Tip and midspan motions of the truss are determined using optical sensors while accelerometers can be used to monitor the motions of other points of interest. Preliminary results indicate that a mix of technologies produces the greatest benefit. For example, shaping the torque profile produces large improvements in slew/settle performance, but without added damping settling times may still be excessive. With the introduction of moderate amounts of damping, slew/settle performance is vastly improved. On the other hand, introducing damping without shaping the torque profile may not yield the desired level of performance

Vitamin D Inhibits Human Immunodeficiency Virus Type 1 and Mycobacterium tuberculosis Infection in Macrophages through the Induction of Autophagy

Low vitamin D levels in human immunodeficiency virus type-1 (HIV) infected persons are associated with more rapid disease progression and increased risk for Mycobacterium tuberculosis infection. We have previously shown that 1α,25-dihydroxycholecalciferol (1,25D3), the active form of vitamin D, inhibits HIV replication in human macrophages through the induction of autophagy. In this study, we report that physiological concentrations of 1,25D3 induce the production of the human cathelicidin microbial peptide (CAMP) and autophagic flux in HIV and M. tuberculosis co-infected human macrophages which inhibits mycobacterial growth and the replication of HIV. Using RNA interference for Beclin-1 and the autophagy-related 5 homologue, combined with the chemical inhibitors of autophagic flux, bafilomycin A1, an inhibitor of autophagosome-lysosome fusion and subsequent acidification, and SID 26681509 an inhibitor of the lysosome hydrolase cathepsin L, we show that the 1,25D3-mediated inhibition of HIV replication and mycobacterial growth during single infection or dual infection is dependent not only upon the induction of autophagy, but also through phagosomal maturation. Moreover, through the use of RNA interference for CAMP, we demonstrate that cathelicidin is essential for the 1,25D3 induced autophagic flux and inhibition of HIV replication and mycobacterial growth. The present findings provide a biological explanation for the benefits and importance of vitamin D sufficiency in HIV and M. tuberculosis-infected persons, and provide new insights into novel approaches to prevent and treat HIV infection and related opportunistic infections

e‐Mental health care for people living with dementia: A lesson on digital equality from COVID‐19

The urgent need to mitigate the mental health consequences for vulnerable groups under pandemic conditions is clear.1 People living with dementia (PLwD) are among the most disadvantaged. The majority of PLwD are older persons with chronic conditions with increased mortality risk, in addition to risks of infection associated with cognitive impairment, which causes difficulties in following personal hygiene instructions.2, 3 The "stay‐at‐home" and visitation restrictions measures save lives, but at a cost to the mental health of PLwD and their carers: when "non‐essential" activities such as psychosocial interventions are cut,4 negative consequences such as loneliness, depression, worsened cognition, agitation, and carer burden3 are logical outcomes, and people are left to their own devices to handle the likely long‐term damage to their mental health

Selective cell death of latently HIV-infected CD4+ T cells mediated by autosis inducing nanopeptides.

Despite significant advances in the treatment of human immunodeficiency virus type-1 (HIV) infection, antiretroviral therapy only suppresses viral replication but is unable to eliminate infection. Thus, discontinuation of antiretrovirals results in viral reactivation and disease progression. A major reservoir of HIV latent infection resides in resting central memory CD4+ T cells (TCM) that escape clearance by current therapeutic regimens and will require novel strategies for elimination. Here, we evaluated the therapeutic potential of autophagy-inducing peptides, Tat-Beclin 1 and Tat-vFLIP-α2, which can induce a novel Na+/K+-ATPase dependent form of cell death (autosis), to kill latently HIV-infected TCM while preventing virologic rebound. In this study, we encapsulated autophagy inducing peptides into biodegradable lipid-coated hybrid PLGA (poly lactic-co-glycolic acid) nanoparticles for controlled intracellular delivery. A single dose of nanopeptides was found to eliminate latent HIV infection in an in vitro primary model of HIV latency and ex vivo using resting CD4+ T cells obtained from peripheral blood mononuclear cells of HIV-infected patients on antiretroviral with fully suppressed virus for greater than 12 months. Notably, increased LC3B lipidation, SQSTM1/p62 degradation and Na+/K+-ATPase activity characteristic of autosis, were detected in nanopeptide treated latently HIV-infected cells compared to untreated uninfected or infected cells. Nanopeptide-induced cell death could be reversed by knockdown of autophagy proteins, ATG5 and ATG7, and inhibition or knockdown of Na+/K+-ATPase. Importantly, viral rebound was not detected following the induction of the Na+/K+-ATPase dependent form of cell death induced by the Tat-Beclin 1 and Tat-vFLIP-α2 nanopeptides. These findings provide a novel strategy to eradicate HIV latently infected resting memory CD4+ T cells, the major reservoir of HIV latency, through the induction of Na+/K+-ATPase dependent autophagy, while preventing reactivation of virus and new infection of uninfected bystander cells

Who knows who we are? Questioning DNA analysis in disaster victim identification

The use of DNA analysis as a mode of identification of disaster victims has become increasingly predominant to other, traditional, methods of identification in recent years. Scientific advances of the technological processes, high-profile use in identification efforts across the globe (such as after 9/11 or in the Asian Tsunami of 2004), and its inclusion in popular media, have led to its popular adoption as one of the primary modes of identification in disaster scenarios, and to the expectation of its use in all cases by the lay public and media. It is increasingly argued to be integral to post-disaster management. However, depending on the circumstances, location, and type of disaster, this technology may not be appropriate, and its use may instead conflict with socio-political and cultural norms and structures of power. Using examples primarily from Cambodia and Iraq this article will explore what these conflicts may be, and in doing so, question the expanding assumption that DNA analysis is a universally appropriate intervention in disaster victim identification. It will argue instead that its use may be a result of a desire for the political and social capital that this highly prestigious technological intervention offers rather than a solely humanitarian intervention on behalf of survivors and the dead

Disruption of pre-mRNA splicing in vivo results in reorganization of splicing factors

We have examined the functional significance of the organization of pre-mRNA splicing factors in a speckled distribution in the mammalian cell nucleus. Upon microinjection into living cells of oligonucleotides or antibodies that inhibit pre-mRNA splicing in vitro, we observed major changes in the organization of splicing factors in vivo. Interchromatin granule clusters became uniform in shape, decreased in number, and increased in both size and content of splicing factors, as measured by immunofluorescence. These changes were transient and the organization of splicing factors returned to their normal distribution by 24 h following microinjection. Microinjection of these oligonucleotides or antibodies also resulted in a reduction of transcription in vivo, but the oligonucleotides did not inhibit transcription in vitro. Control oligonucleotides did not disrupt splicing or transcription in vivo. We propose that the reorganization of splicing factors we observed is the result of the inhibition of splicing in vivo

Separate processing of texture and form in the ventral stream : evidence from fMRI and visual agnosia.

Real-life visual object recognition requires the processing of more than just geometric (shape, size, and orientation) properties. Surface properties such as color and texture are equally important, particularly for providing information about the material properties of objects. Recent neuroimaging research suggests that geometric and surface properties are dealt with separately, within the lateral occipital cortex (LOC) and the collateral sulcus (CoS), respectively. Here we compared objects that either differed in aspect ratio or in surface texture only, keeping all other visual properties constant. Results on brain-intact participants confirmed that surface texture activates an area in the posterior CoS, quite distinct from the area activated by shape within LOC. We also tested two patients with visual object agnosia, one of whom (DF) performed well on the texture task but at chance on the shape task, while the other (MS) showed the converse pattern. This behavioral double dissociation was matched by a parallel neuroimaging dissociation, with activation in CoS but not LOC in patient DF, and activation in LOC but not CoS in patient MS. These data provide presumptive evidence that the areas respectively activated by shape and texture play a causally necessary role in the perceptual discrimination of these features

Control structural interaction testbed: A model for multiple flexible body verification

Conventional end-to-end ground tests for verification of control system performance become increasingly complicated with the development of large, multiple flexible body spacecraft structures. The expense of accurately reproducing the on-orbit dynamic environment and the attendant difficulties in reducing and accounting for ground test effects limits the value of these tests. TRW has developed a building block approach whereby a combination of analysis, simulation, and test has replaced end-to-end performance verification by ground test. Tests are performed at the component, subsystem, and system level on engineering testbeds. These tests are aimed at authenticating models to be used in end-to-end performance verification simulations: component and subassembly engineering tests and analyses establish models and critical parameters, unit level engineering and acceptance tests refine models, and subsystem level tests confirm the models' overall behavior. The Precision Control of Agile Spacecraft (PCAS) project has developed a control structural interaction testbed with a multibody flexible structure to investigate new methods of precision control. This testbed is a model for TRW's approach to verifying control system performance. This approach has several advantages: (1) no allocation for test measurement errors is required, increasing flight hardware design allocations; (2) the approach permits greater latitude in investigating off-nominal conditions and parametric sensitivities; and (3) the simulation approach is cost effective, because the investment is in understanding the root behavior of the flight hardware and not in the ground test equipment and environment

Properties of Ridges in Elastic Membranes

When a thin elastic sheet is confined to a region much smaller than its size the morphology of the resulting crumpled membrane is a network of straight ridges or folds that meet at sharp vertices. A virial theorem predicts the ratio of the total bending and stretching energies of a ridge. Small strains and curvatures persist far away from the ridge. We discuss several kinds of perturbations that distinguish a ridge in a crumpled sheet from an isolated ridge studied earlier (A. E. Lobkovsky, Phys. Rev. E. 53 3750 (1996)). Linear response as well as buckling properties are investigated. We find that quite generally, the energy of a ridge can change by no more than a finite fraction before it buckles.Comment: 13 pages, RevTeX, acknowledgement adde

Group experiences of cognitive stimulation therapy (CST) in Tanzania: a qualitative study

BACKGROUND: Tanzania is a low-income country in which medication for dementia is largely unavailable. Cognitive Stimulation Therapy (CST) is a group-based psychological treatment for people with dementia (PwD), shown to improve cognition and quality of life (QoL). It has previously been culturally adapted and piloted in Tanzania, shown to produce similar outcomes. UK research into CST suggests processes inherent to the group nature are key to its success. This study sought to identify group processes within CST in Tanzania and understand their impact on CST principles and outcomes. METHODS: Data collection took place in rural Hai District, through qualitative semi-structured interviews. Sixteen PwD and four facilitators were recruited through convenience sampling and interviewed about their experiences of CST. Interviews were audio-recorded, translated, transcribed and analysed by thematic analysis. RESULTS: Two main themes emerged: 'Positive group experiences' and 'Negative group experiences'. From this, a number of group processes were identified, such as helping behaviours and feeling understood by the group. Positive processes supported CST principles and participant improvement. Facilitators were influential over group dynamics. The group processes identified impacted CST principles and treatment outcomes. CONCLUSIONS: This is the first study on group mechanisms of CST in Tanzania. It provides deeper insight into participants' experiences of CST, thus identifying specific processes underlying the quantitatively measured positive outcomes of CST in Tanzania by previous studies. It also reveals further cultural barriers to implementation, enabling amendments for optimization of treatment efficacy