Handling Qualities and Trajectory Requirements for Terminal Lunar Landing, as Determined from Analog Simulation

Trajectory requirements for terminal lunar landing from analog simulation of spacecraf

Microwave Assisted Synthesis of Py-Im Polyamides

Microwave synthesis was utilized to rapidly build Py-Im polyamides in high yields and purity using Boc-protection chemistry on Kaiser oxime resin. A representative polyamide targeting the 5′-WGWWCW-3′ (W = A or T) subset of the consensus Androgen and Glucocorticoid Response Elements was synthesized in 56% yield after 20 linear steps and HPLC purification. It was confirmed by Mosher amide derivatization of the polyamide that a chiral α-amino acid does not racemize after several additional coupling steps

Social complexity in bees is not sufficient to explain lack of reversions to solitary living over long time scales

BackgroundThe major lineages of eusocial insects, the ants, termites, stingless bees, honeybees and vespid wasps, all have ancient origins (> or = 65 mya) with no reversions to solitary behaviour. This has prompted the notion of a 'point of no return' whereby the evolutionary elaboration and integration of behavioural, genetic and morphological traits over a very long period of time leads to a situation where reversion to solitary living is no longer an evolutionary option.ResultsWe show that in another group of social insects, the allodapine bees, there was a single origin of sociality > 40 mya. We also provide data on the biology of a key allodapine species, Halterapis nigrinervis, showing that it is truly social. H. nigrinervis was thought to be the only allodapine that was not social, and our findings therefore indicate that there have been no losses of sociality among extant allodapine clades. Allodapine colony sizes rarely exceed 10 females per nest and all females in virtually all species are capable of nesting and reproducing independently, so these bees clearly do not fit the 'point of no return' concept.ConclusionWe argue that allodapine sociality has been maintained by ecological constraints and the benefits of alloparental care, as opposed to behavioural, genetic or morphological constraints to independent living. Allodapine brood are highly vulnerable to predation because they are progressively reared in an open nest (not in sealed brood cells), which provides potentially large benefits for alloparental care and incentives for reproductives to tolerate potential alloparents. We argue that similar vulnerabilities may also help explain the lack of reversions to solitary living in other taxa with ancient social origins.Luke B. Chenoweth, Simon M. Tierney, Jaclyn A. Smith, Steven J.B. Cooper and Michael P. Schwar

The importance of a plume of tidally-mixed water to the biological oceanography of the Gulf of Maine

During the warmer months of the year the eastern Gulf of Maine features a plume of cold water which extends from the tidally well-mixed area adjacent to Grand Manan Island at the mouth of the Bay of Fundy southwest along the Maine coast to well beyond Penobscot Bay. Near Grand Manan Island the plume waters are cold (ca. 10°C), nearly vertically isothermal and carry high concentrations of dissolved inorganic nutrients. The analysis of temperature-salinity diagrams and hydrographic vertical section plots indicate that the deeper waters in Jordan Basin, of slope water origin, upwell and contribute a significant fraction of the high nutrient concentrations. The plume waters become increasingly stratified as they flow to the southwest which leads to a phytoplankton bloom downstream. Nitrate concentrations within the euphotic zone of the plume decrease approximately linearly (ca. 194 mg-at NO3-N · m−2) along a distance of about 130 km travelled after its exit from the Grand Manan area (ca 7.5 days transit time). Cross frontal mixing and tidal flushing along the south and north sides of the plume could account for ca. 18% of this decrease. Total chlorophyll concentrations increase nearly linearly with distance along the first 80 km and then decrease in the following 50 km, presumably the result of phytoplankton being grazed by zooplankton which apparently propagate in response to the increasing chlorophyll levels. Over the distance of increasing chlorophyll concentrations (80 km) the nitrate decrease, corrected for physical losses laterally, would support a new . primary production of 1.46 gm C m−2 d−1. Our analyses suggest that as much as 44% of the new nitrate which enters the Gulf of Maine at depth through the Northeast Channel upwells in the eastern Gulf becoming part of the plume, and hence this feature appears to be very important to the nutrient budget and general biological oceanography of the inner Gulf of Maine

Modulation of NF-κB-dependent gene transcription using programmable DNA minor groove binders

Nuclear factor κB (NF-κB) is a transcription factor that regulates various aspects of immune response, cell death, and differentiation as well as cancer. In this study we introduce the Py-Im polyamide 1 that binds preferentially to the sequences 5′-WGGWWW-3′ and 5′GGGWWW-3′. The compound is capable of binding to κB sites and reducing the expression of various NF-κB–driven genes including IL6 and IL8 by qRT-PCR. Chromatin immunoprecipitation experiments demonstrate a reduction of p65 occupancy within the proximal promoters of those genes. Genome-wide expression analysis by RNA-seq compares the DNA-binding polyamide with the well-characterized NF-κB inhibitor PS1145, identifies overlaps and differences in affected gene groups, and shows that both affect comparable numbers of TNF-α–inducible genes. Inhibition of NF-κB DNA binding via direct displacement of the transcription factor is a potential alternative to the existing antagonists

The Sydney Multisite Intervention of LaughterBosses and ElderClowns (SMILE) study: Cluster randomised trial of humour therapy in nursing homes

Objectives: To determine whether humour therapy reduces depression (primary outcome), agitation and behavioural disturbances and improves social engagement and quality-of-life in nursing home residents. Design: The Sydney Multisite Intervention of LaughterBosses and ElderClowns study was a singleblind cluster randomised controlled trial of humour therapy. Setting: 35 Sydney nursing homes. Participants: All eligible residents within geographically defined areas within each nursing home were invited to participate. Intervention: Professional 'ElderClowns' provided 9-12 weekly humour therapy sessions, augmented by resident engagement by trained staff 'LaughterBosses'. Controls received usual care. Measurements: Depression scores on the Cornell Scale for Depression in Dementia, agitation scores on the Cohen-Mansfield Agitation Inventory, behavioural disturbance scores on the Neuropsychiatric Inventory, social engagement scores on the withdrawal subscale of Multidimensional Observation Scale for Elderly Subjects, and self-rated and proxy-rated quality-of-life scores on a health-related quality-of-life tool for dementia, the DEMQOL. All outcomes were measured at the participant level by researchers blind to group assignment. Randomisation: Sites were stratified by size and level of care then assigned to group using a random number generator. Results: Seventeen nursing homes (189 residents) received the intervention and 18 homes (209 residents) received usual care. Groups did not differ significantly over time on the primary outcome of depression, or on behavioural disturbances other than agitation, social engagement and quality of life. The secondary outcome of agitation was significantly reduced in the intervention group compared with controls over 26 weeks (time by group interaction adjusted for covariates: p=0.011). The mean difference in change from baseline to 26 weeks in Blom-transformed agitation scores after adjustment for covariates was 0.17 (95% CI 0.004 to 0.34, p=0.045). Conclusions: Humour therapy did not significantly reduce depression but significantly reduced agitation

Executive Functioning: Relationship with High School Student Role Performance

BACKGROUND. Student role performance for academic success in secondary education is under represented in the occupational therapy literature, despite the persistently high dropout rate in the United States (Stillwell & Sable, 2013). Executive dysfunction is one of many possible contributors to difficulties in the classroom (Dirette & Kolak, 2004) and is a better indicator of school performance than IQ (Diamond, 2012). This research examined executive functioning of both alternative and traditional high school students to determine if there is a relationship between executive function and academic success as measured by cumulative grade point average. METHOD. 132 high school students from three different school settings were given the Behavioral Rating Inventory of Executive Function-Self Report (BRIEF-SR). The Global Executive Composite (GEC) and individual subscale scores were compared to GPA. RESULTS. No significant difference in GEC scores was found among settings. Subscale scores for “inhibition” and “task completion” were significantly different in the alternative school setting. A weak negative correlation was seen between the GEC and GPA. However, academically unsuccessful students scored statistically lower on the GEC. CONCLUSION. Global executive dysfunction was not predicted by setting but was seen in academically unsuccessful students

Expanding the Repertoire of Natural Product-Inspired Ring Pairs for Molecular Recognition of DNA

A furan amino acid, inspired by the recently discovered proximicin natural products, was incorporated into the scaffold of a DNA-binding hairpin polyamide. While unpaired oligomers of 2,4-disubstituted furan amino acids show poor DNA-binding activity, furan (Fn) carboxamides paired with N-methylpyrrole (Py) and N-methylimidazole (Im) rings demonstrate excellent stabilization of duplex DNA as well as discrimination of noncognate sequences, consistent with function as a Py mimic according to the Py/Im polyamide pairing rules

Potentially Inappropriate Prescribing in Australian Nursing Home Residents with Advanced Dementia: A Substudy of the IDEAL Study

© 2018, Mary Ann Liebert, Inc. Background: Prescribing medications for nursing home residents with advanced dementia should focus on optimizing function and comfort, reducing unnecessary harms and aligning care goals with a palliative approach. Objective: The aim of the study was to estimate the proportion of Australian nursing home residents with advanced dementia receiving potentially inappropriate medications, and identify those most commonly prescribed and factors associated with their use. Design: Data were collected through retrospective audit of medication charts. Setting/Subjects: Two hundred eighteen nursing home residents with advanced dementia from 20 nursing homes participated in a cluster-randomized controlled trial of case conferencing (the IDEAL Study) from June 2013 to December 2014. Measurements: Inappropriate drug use was defined as medications classified as "never appropriate" by the Palliative Excellence in Alzheimer Care Efforts (PEACE) program criteria. Generalized linear mixed models were used to identify variables predicting use of "never" appropriate medications. Results: Over a quarter (n = 65, 30%) of residents received at least one medication classed as "never" appropriate, the most common being lipid-lowering agents (n = 38, 17.4%), antiplatelet agents (n = 18, 8.3%), and acetylcholinesterase inhibitors (n = 16, 7.3%). Residents who had been at the nursing home for ≤10 months (odds ratio [OR] 5.60, 95% confidence interval [CI] 1.74-18.06) and 11-21 months (OR 5.41, 95% CI 1.67-17.75) had significantly greater odds of receiving a never appropriate medication compared with residents who had been at the nursing home for >5 years. Conclusions: Use of potentially inappropriate medications in Australian nursing home residents with advanced dementia is common. A greater understanding of the rationale that underpins prescribing of medications is required

Economic Backwardness and Social Tension

We propose that relative economic backwardness contributes to the build-up of social tension and non-violent and violent conflict. We test our hypothesis using data on organized mass movements and armed civil conflict. The findings show that greater economic backwardness is consistently linked to a higher probability of onset of violent and especially non-violent forms of civil unrest. We provide evidence that the relationship is causal in instrumental variables estimations using new instruments, including mailing speeds and telegram charges around 1900. The magnitude of the effect of backwardness on social tension increases in the two-stage least-squares estimations