A simulation of the instrument pointing system for the Astro-1 mission

NASA has recently completed a shuttle-borne stellar ultraviolet astronomy mission known as Astro-1. A three axis instrument pointing system (IPS) was employed to accurately point the science instruments. In order to analyze the pointing control system and verify pointing performance, a simulation of the IPS was developed using the multibody dynamics software TREETOPS. The TREETOPS IPS simulation is capable of accurately modeling the multibody IPS system undergoing large angle, nonlinear motion. The simulation is documented and example cases are presented demonstrating disturbance rejection, fine pointing operations, and multiple target pointing and slewing of the IPS

Dogs distinguish human intentional and unintentional action

When dogs interact with humans, they often show appropriate reactions to human intentional action. But it is unclear from these everyday observations whether the dogs simply respond to the action outcomes or whether they are able to discriminate between different categories of actions. Are dogs able to distinguish intentional human actions from unintentional ones, even when the action outcomes are the same? We tested dogs’ ability to discriminate these action categories by adapting the so-called “Unwilling vs. Unable” paradigm. This paradigm compares subjects’ reactions to intentional and unintentional human behaviour. All dogs received three conditions: In the unwilling-condition, an experimenter intentionally withheld a reward from them. In the two unable-conditions, she unintentionally withheld the reward, either because she was clumsy or because she was physically prevented from giving the reward to the dog. Dogs clearly distinguished in their spontaneous behaviour between unwilling- and unable-conditions. This indicates that dogs indeed distinguish intentional actions from unintentional behaviour. We critically discuss our findings with regard to dogs’ understanding of human intentional action.Results - Analysis of waiting - Other behavioural reactions Discussion Methods - Ethical statement - Subjects - Experimental set‑up - Procedure - Codin

Machine learning and DSP algorithms for screening of possible osteoporosis using electronic stethoscopes

Osteoporosis is a prevalent but asymptomatic condition that affects a large population of the elderly, resulting in a high risk of fracture. Several methods have been developed and are available in general hospitals to indirectly assess the bone quality in terms of mineral material level and porosity. In this paper we describe a new method that uses a medical reflex hammer to exert testing stimuli, an electronic stethoscope to acquire impulse responses from tibia, and intelligent signal processing based on artificial neural network machine learning to determine the likelihood of osteoporosis. The proposed method makes decisions from the key components found in the time-frequency domain of impulse responses. Using two common pieces of clinical apparatus, this method might be suitable for the large population screening tests for the early diagnosis of osteoporosis, thus avoiding secondary complications. Following some discussions of the mechanism and procedure, this paper details the techniques of impulse response acquisition using a stethoscope and the subsequent signal processing and statistical machine learning algorithms for decision making. Pilot testing results achieved over 80% in detection sensitivity

Acute Oxygen-Sensing via Mitochondria-Generated Temperature Transients in Rat Carotid Body Type I Cells

The Carotid Bodies (CB) are peripheral chemoreceptors that detect changes in arterial oxygenation and, via afferent inputs to the brainstem, correct the pattern of breathing to restore blood gas homeostasis. Herein, preliminary evidence is presented supporting a novel oxygen-sensing hypothesis which suggests CB Type I cell “hypoxic signaling” may in part be mediated by mitochondria-generated thermal transients in TASK-channel-containing microdomains. Distances were measured between antibody-labeled mitochondria and TASK-potassium channels in primary rat CB Type I cells. Sub-micron distance measurements (TASK-1: 0.33 ± 0.04 µm, n = 47 vs TASK-3: 0.32 ± 0.03 µm, n = 54) provided evidence for CB Type I cell oxygen-sensing microdomains. A temperature-sensitive dye (ERthermAC) indicated that inhibition of mitochondrial activity in isolated cells caused a rapid and reversible inhibition of mitochondrial thermogenesis and thus temperature in these microdomains. Whole-cell perforated-patch current-clamp electrophysiological recordings demonstrated sensitivity of resting membrane potential (Vm) to temperature: lowering bath temperature from 37°C to 24°C induced consistent and reversible depolarizations (Vm at 37°C: -48.4 ± 4.11 mV vs 24°C: -31.0 ± 5.69 mV; n = 5; p \u3c 0.01). These data suggest that hypoxic inhibition of mitochondrial thermogenesis may play an important role in oxygen chemotransduction in the CB. A reduction in temperature within cellular microdomains will inhibit plasma membrane ion channels, influence the balance of cellular phosphorylation–dephosphorylation, and may extend the half-life of reactive oxygen species. The characterization of a thermosensory chemotransduction mechanism, that may also be used by other oxygen-sensitive cell types and may impact multiple other chemotransduction mechanisms is critical if we are to fully understand how the CBs, and potentially other oxygen-sensitive cells, respond to hypoxia

Placental Leucine Aminopeptidase- and Aminopeptidase A- Deficient Mice Offer Insight concerning the Mechanisms Underlying Preterm Labor and Preeclampsia

Preeclampsia and preterm delivery are important potential complications in pregnancy and represent the leading causes for maternal and perinatal morbidity and mortality. The mechanisms underlying both diseases remain unknown, thus available treatments (beta2-stimulants and magnesium sulfate) are essentially symptomatic. Both molecules have molecular weights less than 5–8 kDa, cross the placental barrier, and thus exert their effects on the fetus. The fetus produces peptides that are highly vasoactive and uterotonic and increase in response to maternal stress and with continued development. Fetal peptides are also small molecules that inevitably leak across into the maternal circulation. Aminopeptidases such as placental leucine aminopeptidase (P-LAP) and aminopeptidase A (APA) are large molecules that do not cross the placental barrier. We have shown that APA acts as an antihypertensive agent in the pregnant spontaneously hypertensive rat by degrading vasoactive peptides and as a result returns the animal to a normotensive state. P-LAP also acts as an antiuterotonic agent by degrading uterotonic peptides and thus prolongs gestation in the pregnant mouse. Given the ever increasing worldwide incidences of preeclampsia and preterm labor, it is imperative that new agents be developed to safely prolong gestation. We believe that the use of aminopeptidases hold promise in this regard

Ethanol and Opioids Do Not Act Synergistically To Depress Excitation in Carotid Body Type I Cells

The combination of opioids and ethanol can synergistically depress breathing and the acute ventilatory response to hypoxia. Multiple studies have shown that the underlying mechanisms for this may involve calcium channel inhibition in central neurons. But we have previously identified opioid receptors in the carotid bodies and shown that their activation inhibits calcium influx into the chemosensitive cells. Given that the carotid bodies contribute to the drive to breathe and underpin the acute hypoxic ventilatory response, we hypothesized that ethanol and opioids may act synergistically in these peripheral sensory organs to further inhibit calcium influx and therefore inhibit ventilation. Methods Carotid bodies were removed from 56 Sprague–Dawley rats (1021 days old) and then enzymatically dissociated to allow calcium imaging of isolated chemosensitive type I cells. Cells were stimulated with high K+ in the presence and absence of the µ-opioid agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) (10 µM), a maximal sublethal concentration of ethanol (3 g L-1, 65.1 mM) or a combination of both. Results DAMGO alone significantly inhibited Ca2+ influx but this effect was not potentiated by the high concentration of ethanol. Conclusion These results indicate for the first time that while opioids may suppress breathing via an action at the level of the carotid bodies, ethanol is unlikely to potentiate inhibition via this pathway. Thus, the synergistic effects of ethanol and opioids on ventilatory parameters are likely mediated by central rather than peripheral actions

Detection of osteoporosis from percussion responses using an electronic stethoscope and machine learning

Osteoporosis is an asymptomatic bone condition that affects a large proportion of the elderly population around the world, resulting in increased bone fragility and increased risk of fracture. Previous studies had shown that the vibroacoustic response of bone can indicate the quality of the bone condition. Therefore, the aim of the authors' project is to develop a new method to exploit this phenomenon to improve detection of osteoporosis in individuals. In this paper a method is described that uses a reflex hammer to exert testing stimuli on a patient's tibia and an electronic stethoscope to acquire the impulse responses. The signals are processed as mel frequency cepstrum coefficients and passed through an artificial neural network to determine the likelihood of osteoporosis from the tibia's impulse responses. Following some discussions of the mechanism and procedure, this paper details the signal acquisition using the stethoscope and the subsequent signal processing and the statistical machine learning algorithm. Pilot testing with 12 patients achieved over 80% sensitivity with a false positive rate below 30% and accuracies in the region of 70%. An extended dataset of 110 patients achieved an error rate of 30% with some room for improvement in the algorithm. By using common clinical apparatus and strategic machine learning, this method might be suitable as a large population screening test for the early diagnosis of osteoporosis, thus avoiding secondary complications

Multigenerational analysis of sex-specific phenotypic differences at midgestation caused by abnormal folate metabolism

The exposure to adverse environmental conditions (e.g., poor nutrition) may lead to increased disease risk in an individual and their descendants. In some cases, the results may be sexually dimorphic. A range of phenotypes has been associated with deficiency in or defective metabolism of the vitamin folate. However, the molecular mechanism linking folate metabolism to development is still not well defined nor is it clear whether phenotypes are sex-specific. The enzyme methionine synthase reductase (MTRR) is required for the progression of folate metabolism and the utilization of methyl groups from the folate cycle. Previously, we showed that the hypomorphic Mtrrgt mutation in mice results in metabolic disruption, epigenetic instability, and a wide spectrum of developmental phenotypes (e.g., growth defects, congenital malformations) at midgestation that appear in subsequent wildtype generations. This transgenerational effect only occurs through the maternal lineage. Here, we explore whether the phenotypes that result from either intrinsic or ancestral Mtrr deficiency are sexually dimorphic. We found that no sexual dimorphism is apparent in either situation when the phenotypes were broadly or specifically defined. However, when we focused on the group of phenotypically normal conceptuses derived from maternal grandparental Mtrr deficiency, we observed an apparent increase in placental efficiency in each subsequent generation leading to F4 generation female embryos that weigh more than controls. These data suggest that ancestral abnormal folate metabolism may lead to male grandprogeny that are less able to adapt or female grandprogeny that are programmed to become more sensitive to folate availability in subsequent generations.The following support was given: a Centre for Trophoblast Research (CTR) studentship to N.P., a Royal Society Newton International Fellowship to J.R., a Newnham College (Cambridge) studentship to K.M, and a Wellcome Trust 4-year PhD studentship in Developmental Mechanisms to G.E.T.B. This work was funded by a CTR Next Generation Fellowship, a Lister Research Prize, and an Isaac Newton Trust/Wellcome Trust ISSF/University of Cambridge joint research grant (to E.D.W.)

Chimpanzees prepare for alternative possible outcomes

When facing uncertainty, humans often build mental models of alternative outcomes. Considering diverging scenarios allows agents to respond adaptively to different actual worlds by developing contingency plans (covering one's bases). In a pre-registered experiment, we tested whether chimpanzees (Pan troglodytes) prepare for two mutually exclusive possibilities. Chimpanzees could access two pieces of food, but only if they successfully protected them from a human competitor. In one condition, chimpanzees could be certain about which piece of food the human experimenter would attempt to steal. In a second condition, either one of the food rewards was a potential target of the competitor. We found that chimpanzees were significantly more likely to protect both pieces of food in the second relative to the first condition, raising the possibility that chimpanzees represent and prepare effectively for different possible worlds.PostprintPeer reviewe