Wind tunnel tests of Space Shuttle external tank insulation material in the aerothermal tunnel at elevated (1440 deg F) total temperatures

Tests of the space shuttle external tank foam insulation were conducted in the von Karman Gas Dynamics Facility Tunnel C. For these tests, Tunnel C was run at Mach 4 with a total temperature of 1440 F and a total pressure which varied from 30-100 psia. Cold wall heating rates were changed by varying the test article support wedge angle and by adding and removing a shock generator or a cylindrical protuberance. Selected results are presented to illustrate the test techniques and typical data obtained

Titanocene anticancer complexes and their binding mode of action to human serum albumin: a computational study

Due to the pivotal role played by human serum albumin (HSA) in the transport and cytotoxicity of titanocene complexes, a docking study has been performed on a selected set of titanocene complexes to aid in the current understanding of the potential mode of action of these titanocenes upon binding HSA. Analysis of the docking results has revealed potential binding at the known drug binding sites in HSA and has provided some explanation for the specificity and subsequent cytotoxicity of these titanocenes. Additionally, a new alternative binding site for these titanocenes has been postulated

Wind tunnel tests of space shuttle solid rocket booster insulation material in the aerothermal tunnel c

Wind tunnel tests of the space shuttle Solid Rocket Booster Insulation were conducted in the von Karman Gas Dynamics Facility Tunnel C. For these tests, Tunnel C was run at Mach 4 with a total temperature of 1100-1440 and a total pressure of 100 psia. Cold wall heating rates were changed by varying the test article support wedge angle. Selected results are presented to illustrate the test techniques and typical data obtained

A COMPARATIVE STUDY BETWEEN BLADES AND STUDS IN FOOTBALL BOOTS

The incidence of non-contact injuries in football is high. A significant proportion of the blame is aimed at the footwear worn. Bladed design boots have attracted criticism, with high profile sports teams banning them amid fears of causing knee injury BBC, 2009). This study aimed to biomechanically compare a bladed boot design with a more conventional studded boot design to assess if either boot type produces a greater muscle response and suggest their potential for causing non-contact injury

Ab initio Study of Misfit Dislocations at the SiC/Si(001) Interface

The high lattice mismatched SiC/Si(001) interface was investigated by means of combined classical and ab initio molecular dynamics. Among the several configurations analyzed, a dislocation network pinned at the interface was found to be the most efficient mechanism for strain relief. A detailed description of the dislocation core is given, and the related electronic properties are discussed for the most stable geometry: we found interface states localized in the gap that may be a source of failure of electronic devices

Magnetic resonance imaging-guided phase 1 trial of putaminal AADC gene therapy for Parkinson's disease.

ObjectiveTo understand the safety, putaminal coverage, and enzyme expression of adeno-associated viral vector serotype-2 encoding the complementary DNA for the enzyme, aromatic L-amino acid decarboxylase (VY-AADC01), delivered using novel intraoperative monitoring to optimize delivery.MethodsFifteen subjects (three cohorts of 5) with moderately advanced Parkinson's disease and medically refractory motor fluctuations received VY-AADC01 bilaterally coadministered with gadoteridol to the putamen using intraoperative magnetic resonance imaging (MRI) guidance to visualize the anatomic spread of the infusate and calculate coverage. Cohort 1 received 8.3 × 1011 vg/ml and ≤450 μl per putamen (total dose, ≤7.5 × 1011 vg); cohort 2 received the same concentration (8.3 × 1011 vg/ml) and ≤900 μl per putamen (total dose, ≤1.5 × 1012 vg); and cohort 3 received 2.6 × 1012 vg/ml and ≤900 μl per putamen (total dose, ≤4.7 × 1012 vg). (18)F-fluoro-L-dihydroxyphenylalanine positron emission tomography (PET) at baseline and 6 months postprocedure assessed enzyme activity; standard assessments measured clinical outcomes.ResultsMRI-guided administration of ascending VY-AADC01 doses resulted in putaminal coverage of 21% (cohort 1), 34% (cohort 2), and 42% (cohort 3). Cohorts 1, 2, and 3 showed corresponding increases in enzyme activity assessed by PET of 13%, 56%, and 79%, and reductions in antiparkinsonian medication of -15%, -33%, and -42%, respectively, at 6 months. At 12 months, there were dose-related improvements in clinical outcomes, including increases in patient-reported ON-time without troublesome dyskinesia (1.6, 3.3, and 1.5 hours, respectively) and quality of life.InterpretationNovel intraoperative monitoring of administration facilitated targeted delivery of VY-AADC01 in this phase 1 study, which was well tolerated. Increases in enzyme expression and clinical improvements were dose dependent. ClinicalTrials.gov Identifier: NCT01973543 Ann Neurol 2019;85:704-714

Associations between mobility, cognition and callosal integrity in people with parkinsonism

Falls in people with parkinsonism are likely related to both motor and cognitive impairments. In addition to idiopathic Parkinson\u27s disease (PD), some older adults have lower body parkinsonism (a frontal gait disorder), characterized by impaired lower extremity balance and gait as well as cognition, but without tremor or rigidity. Neuroimaging during virtual gait suggests that interhemispheric, prefrontal cortex communication may be involved in locomotion, but contributions of neuroanatomy connecting these regions to objective measures of gait in people with parkinsonism remains unknown. Our objectives were to compare the integrity of fiber tracts connecting prefrontal and sensorimotor cortical regions via the corpus callosum in people with two types of parkinsonism and an age-matched control group and to relate integrity of these callosal fibers with clinical and objective measures of mobility and cognition. We recruited 10 patients with frontal gait disorders, 10 patients with idiopathic PD and 10 age-matched healthy control participants. Participants underwent cognitive and mobility testing as well as diffusion weighted magnetic resonance imaging to quantify white matter microstructural integrity of interhemispheric fiber tracts. People with frontal gait disorders displayed poorer cognitive performance and a slower, wider-based gait compared to subjects with PD and age-matched control subjects. Despite a widespread network of reduced white matter integrity in people with frontal gait disorders, gait and cognitive deficits were solely related to interhemispheric circuitry employing the genu of the corpus callosum. Current results highlight the importance of prefrontal interhemispheric communication for lower extremity control in neurological patients with cognitive dysfunction

Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression

RATIONALE: Depressed patients robustly exhibit affective biases in emotional processing which are altered by SSRIs and predict clinical outcome. OBJECTIVES: The objective of this study is to investigate whether psilocybin, recently shown to rapidly improve mood in treatment-resistant depression (TRD), alters patients' emotional processing biases. METHODS: Seventeen patients with treatment-resistant depression completed a dynamic emotional face recognition task at baseline and 1 month later after two doses of psilocybin with psychological support. Sixteen controls completed the emotional recognition task over the same time frame but did not receive psilocybin. RESULTS: We found evidence for a group × time interaction on speed of emotion recognition (p = .035). At baseline, patients were slower at recognising facial emotions compared with controls (p < .001). After psilocybin, this difference was remediated (p = .208). Emotion recognition was faster at follow-up compared with baseline in patients (p = .004, d = .876) but not controls (p = .263, d = .302). In patients, this change was significantly correlated with a reduction in anhedonia over the same time period (r = .640, p = .010). CONCLUSIONS: Psilocybin with psychological support appears to improve processing of emotional faces in treatment-resistant depression, and this correlates with reduced anhedonia. Placebo-controlled studies are warranted to follow up these preliminary findings

Tryptophan metabolism in the central nervous system: medical implications

The metabolism of the amino acid L-tryptophan is a highly regulated physiological process leading to the generation of several neuroactive compounds within the central nervous system. These include the aminergic neurotransmitter serotonin (5-hydroxytryptamine, 5-HT), products of the kynurenine pathway of tryptophan metabolism (including 3-hydroxykynurenine, 3-hydroxyanthranilic acid, quinolinic acid and kynurenic acid), the neurohormone melatonin, several neuroactive kynuramine metabolites of melatonin, and the trace amine tryptamine. The integral role of central serotonergic systems in the modulation of physiology and behaviour has been well documented since the first description of serotonergic neurons in the brain some 40 years ago. However, while the significance of the peripheral kynurenine pathway of tryptophan metabolism has also been recognised for several decades, it has only recently been appreciated that the synthesis of kynurenines within the central nervous system has important consequences for physiology and behaviour. Altered kynurenine metabolism has been implicated in the pathophysiology of conditions such as acquired immunodeficiency syndrome (AIDS)-related dementia, Huntington's disease and Alzheimer's disease. In this review we discuss the molecular mechanisms involved in regulating the metabolism of tryptophan and consider the medical implications associated with dysregulation of both serotonergic and kynurenine pathways of tryptophan metabolism