Hybrid Differential Dynamic Programming Algorithm for Low-Thrust Trajectory Design Using Exact High-Order Transition Maps

Optimal orbital trajectories are obtained through the solution of highly nonlinear large-scale problems. In the case of low-thrust propulsion applications, the spacecraft benefits from high specific impulses and, hence, greater payload mass. However, these missions require a high count of orbital revolutions and, therefore, display augmented sensitivity to many disturbances. Solutions to such problems can be tackled via a discrete approach, using optimal feedback control laws. Historically, differential dynamic programming (DDP) has shown outstanding results in tackling these problems. A state of the art software that implements a variation of DDP has been developed by Whiffen (2006) and it is used by NASA’s DAWN mission. One of the latest techniques implemented to deal with these discrete constrained optimizations is the Hybrid Differential Dynamic Programming (HDDP) algorithm, introduced by Lantoine and Russell (2012). This method complements the reliability and efficiency of classic nonlinear programming techniques with the robustness to poor initial guesses and the reduced computational effort of DDP. The key feature of the algorithm is the exploitation of a second order state transition matrix procedure to propagate the needed partials, decoupling the dynamics from the optimization. In doing so, it renders the integration of dynamical equations suitable for parallelization. Together with the possibility to treat constrained problems, this represents the greatest improvement of classic DDP. Nevertheless, the major limitation of this approach is the high computational cost to evaluate the required state transition matrices. Analytical derivatives, when available, have shown a significant reduction in the computational cost and time for HDDP application. This work applies differential algebra (DA) to HDDP to cope with this limitation. DA is introduced to obtain state transition matrices as polynomial maps. These maps come directly from the integration of the dynamics of the system, removing the dedicated algorithmic step and reducing its computational cost. Moreover, by operating on polynomial maps, all the solutions of local optimization problems are treated through differential algebraic techniques. This approach allows users to deal with higher order expansions of the cost, without modifying the algorithm. From the examples provided, it emerges that increasing the order of the expansions does not yield a better convergence rate. Additionally, it causes numerical instability of the algorithm to arise, as well as a noticeable increase on computational time due to the number of polynomial coefficients that ought to be computed

A CTNNA3 compound heterozygous deletion implicates a role for \u3b1T-catenin in susceptibility to autism spectrum disorder.

Autism spectrum disorder (ASD) is a highly heritable, neurodevelopmental condition showing extreme genetic heterogeneity. While it is well established that rare genetic variation, both de novo and inherited, plays an important role in ASD risk, recent studies also support a rare recessive contribution. METHODS: We identified a compound heterozygous deletion intersecting the CTNNA3 gene, encoding \u3b1T-catenin, in a proband with ASD and moderate intellectual disability. The deletion breakpoints were mapped at base-pair resolution, and segregation analysis was performed. We compared the frequency of CTNNA3 exonic deletions in 2,147 ASD cases from the Autism Genome Project (AGP) study versus the frequency in 6,639 controls. Western blot analysis was performed to get a quantitative characterisation of Ctnna3 expression during early brain development in mouse. RESULTS: The CTNNA3 compound heterozygous deletion includes a coding exon, leading to a putative frameshift and premature stop codon. Segregation analysis in the family showed that the unaffected sister is heterozygote for the deletion, having only inherited the paternal deletion. While the frequency of CTNNA3 exonic deletions is not significantly different between ASD cases and controls, no homozygous or compound heterozygous exonic deletions were found in a sample of over 6,000 controls. Expression analysis of Ctnna3 in the mouse cortex and hippocampus (P0-P90) provided support for its role in the early stage of brain development. CONCLUSION: The finding of a rare compound heterozygous CTNNA3 exonic deletion segregating with ASD, the absence of CTNNA3 homozygous exonic deletions in controls and the high expression of Ctnna3 in both brain areas analysed implicate CTNNA3 in ASD susceptibility

ELMOD3-SH2D6 gene fusion as a possible co-star actor in autism spectrum disorder scenario

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by high heritability. It is known that genetic factors contribute to ASD pathogenesis. In particular, copy number variants (CNVs) are involved in ASD susceptibility and can affect gene expression regulation. 2p11.2 microdeletions encompassing ELMOD3, CAPG and SH2D6 genes have been described in four unrelated ASD families. The present study revealed that this microdeletion is responsible for the production of a chimeric transcript generated from the fusion between ELMOD3 and SH2D6. The identified transcript showed significantly higher expression levels in subjects carrying the deletion compared to control subjects, suggesting that it is not subjected to nonsense-mediated decay and might encode for a chimeric protein. In conclusion, this study suggests the possible involvement of this gene fusion, together with the other previously identified variants, in ASD

Comparison of Protein- or Amino Acid-Based Supplements in the Rehabilitation of Men with Severe Obesity: A Randomized Controlled Pilot Study

Background: Weight loss is associated with a reduction in all body compartments, including muscle mass (MM), and this effect produces a decrease in function and muscle strength. Our objective was to assess the impact of protein or amino acid supplements on MM loss in middle-aged men (age 35 kg/m2) during weight loss. Materials and Methods: We conducted a single-site randomized controlled trial (Clinicaltrials.gov NCT05143398) with 40 in-patient male subjects with severe obesity. Participants underwent an intervention program consisting of a low-calorie balanced diet and structured physical activity. They were randomly assigned to 4-week treatment groups: (1) control (CTR, N = 10), (2) protein (P, N = 10), (3) branched-chain amino acid (BCAA, N = 10), and (4) essential amino acid mixture with tricarboxylic acid cycle intermediates (PD-E07, N = 10) supplementation. Results: Following 4 weeks of intervention, all groups showed similar reductions in body weight compared to baseline. When examining the delta values, a notable increase in muscle mass (MM) was observed in the PD-E07 intervention group [MM (kg): 2.84 ± 3.57; MM (%): 3.63 ± 3.14], in contrast to the CTR group [MM (kg): −2.46 ± 3.04; MM (%): −0.47 ± 2.28], with a statistical significance of p = 0.045 and p = 0.023, respectively. However, the MM values for the P group [MM (kg): −2.75 ± 5.98, p = 0.734; MM (%): −0.44 ± 4.02, p = 0.990] and the BCAA group [MM (kg): −1 ± 3.3, p = 0.734; MM (%): 0.34 ± 2.85, p = 0.956] did not exhibit a statistically significant difference when compared to the CTR group. Conclusions: Amino acid-based supplements may effectively mitigate the loss of MM typically observed during weight reduction. Further validation through large-scale studies is necessary

Prevention of cardiovascular disease. screening for magnesium deficiency

Magnesium is an essential mineral naturally present in the human body, where it acts as cofactor in several enzymatic reactions. Magnesium is a key cardiovascular regulator, which maintains electrical, metabolic, and vascular homeostasis. Moreover, magnesium participates in inflammation and oxidative processes. In fact, magnesium deficiency is involved in the pathophysiology of arterial hypertension, diabetes mellitus, dyslipidemia, metabolic syndrome, endothelial dysfunction, coronary artery disease, cardiac arrhythmias, and sudden cardiac death. In consideration of the great public-health impact of cardiovascular disease, the recognition of the negative effects of magnesium deficiency suggests the possible role of hypomagnesaemia as cardiovascular risk factor and the use of serum magnesium level for the screening and prevention of cardiovascular risk factors and cardiovascular diseases. Moreover, it might help with the identification of new therapeutical strategies for the management of cardiovascular disease through magnesium supplementation

Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment

Peer reviewedPublisher PD

Aminoglycoside antibiotics and autism: a speculative hypothesis

BACKGROUND: Recently, it has been suspected that there is a relationship between therapy with some antibiotics and the onset of autism; but even more curious, some children benefited transiently from a subsequent treatment with a different antibiotic. Here, we speculate how aminoglycoside antibiotics might be associated with autism. PRESENTATION: We hypothesize that aminoglycoside antibiotics could a) trigger the autism syndrome in susceptible infants by causing the stop codon readthrough, i.e., a misreading of the genetic code of a hypothetical critical gene, and/or b) improve autism symptoms by correcting the premature stop codon mutation in a hypothetical polymorphic gene linked to autism. TESTING: Investigate, retrospectively, whether a link exists between aminoglycoside use (which is not extensive in children) and the onset of autism symptoms (hypothesis "a"), or between amino glycoside use and improvement of these symptoms (hypothesis "b"). Whereas a prospective study to test hypothesis "a" is not ethically justifiable, a study could be designed to test hypothesis "b". IMPLICATIONS: It should be stressed that at this stage no direct evidence supports our speculative hypothesis and that its main purpose is to initiate development of new ideas that, eventually, would improve our understanding of the pathobiology of autism

Homozygosity for a missense mutation in the 67 kDa isoform of glutamate decarboxylase in a family with autosomal recessive spastic cerebral palsy: parallels with Stiff-Person Syndrome and other movement disorders

Background Cerebral palsy (CP) is an heterogeneous group of neurological disorders of movement and/or posture, with an estimated incidence of 1 in 1000 live births. Non-progressive forms of symmetrical, spastic CP have been identified, which show a Mendelian autosomal recessive pattern of inheritance. We recently described the mapping of a recessive spastic CP locus to a 5 cM chromosomal region located at 2q24-31.1, in rare consanguineous families. Methods Here we present data that refine this locus to a 0.5 cM region, flanked by the microsatellite markers D2S2345 and D2S326. The minimal region contains the candidate gene GAD1, which encodes a glutamate decarboxylase isoform (GAD67), involved in conversion of the amino acid and excitatory neurotransmitter glutamate to the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Results A novel amino acid mis-sense mutation in GAD67 was detected, which segregated with CP in affected individuals. Conclusions This result is interesting because auto-antibodies to GAD67 and the more widely studied GAD65 homologue encoded by the GAD2 gene, are described in patients with Stiff-Person Syndrome (SPS), epilepsy, cerebellar ataxia and Batten disease. Further investigation seems merited of the possibility that variation in the GAD1 sequence, potentially affecting glutamate/GABA ratios, may underlie this form of spastic CP, given the presence of anti-GAD antibodies in SPS and the recognised excitotoxicity of glutamate in various contexts