U.S. Coast Guard Boat Recovery Simulation at NASA Ames Vertical Motion Simulator

The Boat Recovery Simulation was a collaboration between the U.S. Coast Guard and NASA. The experiment was conducted at the NASA Ames Vertical Motion Simulator (VMS). The goals were to (1) design a VMS experiment that can accurately simulate the motion of high sea conditions and to (2) collect data for the U.S. Coast Guard on human performance related to small boat recovery operations. The experiment setup included a software operation model designed around empirical boat position data; a replica boat section manufactured to incorporate real-world task elements; and the means to collect objective and subjective data from human participants. The VMS provided a viable testbed to assess certified U.S. Coast Guard crewmembers task performance while in motion

Adiponectin Deficiency Impairs Maternal Metabolic Adaptation to Pregnancy in Mice.

Hypoadiponectinemia has been widely observed in patients with gestational diabetes mellitus (GDM). To investigate the causal role of hypoadiponectinemia in GDM, adiponectin gene knockout (Adipoq-/- ) and wild-type (WT) mice were crossed to produce pregnant mouse models with or without adiponectin deficiency. Adenoviral vector-mediated in vivo transduction was used to reconstitute adiponectin during late pregnancy. Results showed that Adipoq-/- dams developed glucose intolerance and hyperlipidemia in late pregnancy. Increased fetal body weight was detected in Adipoq-/- dams. Adiponectin reconstitution abolished these metabolic defects in Adipoq-/- dams. Hepatic glucose and triglyceride production rates of Adipoq-/- dams were significantly higher than those of WT dams. Robustly enhanced lipolysis was found in gonadal fat of Adipoq-/- dams. Interestingly, similar levels of insulin-induced glucose disposal and insulin signaling in metabolically active tissues in Adipoq-/- and WT dams indicated that maternal adiponectin deficiency does not reduce insulin sensitivity. However, remarkably decreased serum insulin concentrations were observed in Adipoq-/- dams. Furthermore, β-cell mass, but not glucose-stimulated insulin release, in Adipoq-/- dams was significantly reduced compared with WT dams. Together, these results demonstrate that adiponectin plays an important role in controlling maternal metabolic adaptation to pregnancy

Photon Counting Using Edge-Detection Algorithm

New applications such as high-datarate, photon-starved, free-space optical communications require photon counting at flux rates into gigaphoton-per-second regimes coupled with subnanosecond timing accuracy. Current single-photon detectors that are capable of handling such operating conditions are designed in an array format and produce output pulses that span multiple sample times. In order to discern one pulse from another and not to overcount the number of incoming photons, a detection algorithm must be applied to the sampled detector output pulses. As flux rates increase, the ability to implement such a detection algorithm becomes difficult within a digital processor that may reside within a field-programmable gate array (FPGA). Systems have been developed and implemented to both characterize gigahertz bandwidth single-photon detectors, as well as process photon count signals at rates into gigaphotons per second in order to implement communications links at SCPPM (serial concatenated pulse position modulation) encoded data rates exceeding 100 megabits per second with efficiencies greater than two bits per detected photon. A hardware edge-detection algorithm and corresponding signal combining and deserialization hardware were developed to meet these requirements at sample rates up to 10 GHz. The photon discriminator deserializer hardware board accepts four inputs, which allows for the ability to take inputs from a quadphoton counting detector, to support requirements for optical tracking with a reduced number of hardware components. The four inputs are hardware leading-edge detected independently. After leading-edge detection, the resultant samples are ORed together prior to deserialization. The deserialization is performed to reduce the rate at which data is passed to a digital signal processor, perhaps residing within an FPGA. The hardware implements four separate analog inputs that are connected through RF connectors. Each analog input is fed to a high-speed 1-bit comparator, which digitizes the input referenced to an adjustable threshold value. This results in four independent serial sample streams of binary 1s and 0s, which are ORed together at rates up to 10 GHz. This single serial stream is then deserialized by a factor of 16 to create 16 signal lines at a rate of 622.5 MHz or lower for input to a high-speed digital processor assembly. The new design and corresponding hardware can be employed with a quad-photon counting detector capable of handling photon rates on the order of multi-gigaphotons per second, whereas prior art was only capable of handling a single input at 1/4 the flux rate. Additionally, the hardware edge-detection algorithm has provided the ability to process 3-10 higher photon flux rates than previously possible by removing the limitation that photoncounting detector output pulses on multiple channels being ORed not overlap. Now, only the leading edges of the pulses are required to not overlap. This new photon counting digitizer hardware architecture supports a universal front end for an optical communications receiver operating at data rates from kilobits to over one gigabit per second to meet increased mission data volume requirements

Takotsubo Cardiomyopathy: A Case Series and Review of the Literature

Takotsubo cardiomyopathy (TCM) is an unusual form of acute cardiomyopathy showing left ventricular apical ballooning. It is often triggered by intense physical or emotional distress. We report here four cases of TCM and a review of the literature on the topic

Functional plasticity of antibacterial EndoU toxins.

Bacteria use several different secretion systems to deliver toxic EndoU ribonucleases into neighboring cells. Here, we present the first structure of a prokaryotic EndoU toxin in complex with its cognate immunity protein. The contact-dependent growth inhibition toxin CdiA-CTSTECO31 from Escherichia coli STEC_O31 adopts the eukaryotic EndoU fold and shares greatest structural homology with the nuclease domain of coronavirus Nsp15. The toxin contains a canonical His-His-Lys catalytic triad in the same arrangement as eukaryotic EndoU domains, but lacks the uridylate-specific ribonuclease activity that characterizes the superfamily. Comparative sequence analysis indicates that bacterial EndoU domains segregate into at least three major clades based on structural variations in the N-terminal subdomain. Representative EndoU nucleases from clades I and II degrade tRNA molecules with little specificity. In contrast, CdiA-CTSTECO31 and other clade III toxins are specific anticodon nucleases that cleave tRNAGlu between nucleotides C37 and m2 A38. These findings suggest that the EndoU fold is a versatile scaffold for the evolution of novel substrate specificities. Such functional plasticity may account for the widespread use of EndoU effectors by diverse inter-bacterial toxin delivery systems

Combined systemic and ocular chemotherapy for anterior segment metastasis of systemic mantle cell lymphoma.

BACKGROUND: Mantle cell lymphoma (MCL) is an aggressive subtype of non-Hodgkin\u27s lymphoma that rarely metastasizes to the iris and the anterior segment. Blastic/pleomorphic morphology is thought to have an adverse effect on prognosis in MCL. MCL is resistant to conventional chemotherapeutic regimens with a tendency for multiple relapses. Management of anterior segment metastasis of systemic MCL has not been described in literature. FINDINGS: A 58-year-old male presented with an aggressive, relapsing, metastatic, systemic blastic variant of MCL with ocular involvement. At the time of initial presentation, large tumor cells were visible in the anterior chamber (AC) along with hypopyon and fibrin. The AC cells stained positively for CD20. The iris was thickened and coated with lymphoma cells. Iris neovascularization was present. Given extensive systemic and ocular involvement, the patient was given combination chemotherapy with systemic ibrutinib and intravitreal injections of methotrexate and rituximab. The disease response was monitored using multimodal imaging, including anterior segment optical coherence tomography and ultrasound biomicroscopy. Following combination of systemic and intraocular chemotherapy, there was a marked decrease in the ocular tumor load and the systemic disease. CONCLUSIONS: Combination therapy with intravitreal injections of chemotherapeutic agents targeting monoclonal B-cell population and novel systemic agents may help to achieve remission in anterior segment metastasis of aggressive subtypes of NHL such as blastic variant of MCL. Multimodal imaging may assist in the management of these cases

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Smooth Muscle Stiffness Sensitivity is Driven by Soluble and Insoluble ECM Chemistry

Smooth muscle cell (SMC) invasion into plaques and subsequent proliferation is a major factor in the progression of atherosclerosis. During disease progression, SMCs experience major changes in their microenvironment, such as what integrin-binding sites are exposed, the portfolio of soluble factors available, and the elasticity and modulus of the surrounding vessel wall. We have developed a hydrogel biomaterial platform to examine the combined effect of these changes on SMC phenotype. We were particularly interested in how the chemical microenvironment affected the ability of SMCs to sense and respond to modulus. To our surprise, we observed that integrin binding and soluble factors are major drivers of several critical SMC behaviors, such as motility, proliferation, invasion, and differentiation marker expres- sion, and these factors modulated the effect of stiffness on proliferation and migration. Overall, modulus only modestly affected behaviors other than proliferation, relative to integrin binding and soluble factors. Surprisingly, patho- logical behaviors (proliferation, motility) are not inversely related to SMC marker expression, in direct conflict with previous studies on substrates coupled with single extracel- lular matrix (ECM) proteins. A high-throughput bead-based ELISA approach and inhibitor studies revealed that differ- entiation marker expression is mediated chiefly via focal adhesion kinase (FAK) signaling, and we propose that integrin binding and FAK drive the transition from a migratory to a proliferative phenotype. We emphasize the importance of increasing the complexity of in vitro testing platforms to capture these subtleties in cell phenotypes and signaling, in order to better recapitulate important features of in vivo disease and elucidate potential context-dependent therapeutic targets

Is a Two-Day Cardiopulmonary Exercise Test a Valid Tool for The Diagnosis of Post-Exertional Malaise in Long COVID?

A two-day cardiopulmonary exercise testing (CPET) protocol (maximal ramp-incremental cycle test repeated 24hr apart) in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients has suggested that day-2 performance is decreased relative to day-1. This difference has been attributed to post-exertional malaise (PEM), suggesting the two-day CPET as a protocol to investigate PEM in Long COVID (LC) patients. PURPOSE: We aimed to investigate any effects of PEM on exercise performance and cardiorespiratory and perceptual responses to a two-day CPET in LC patients to determine whether the day-1 CPET would impair performance, cardiorespiratory responses or perceptions of exercise at day-2. METHODS: Fifteen LC patients with one or more symptoms persisting for more than three months after their initial infection [n=7 females; n=1 hospitalized; mean(SD); age 53(11) yrs; body mass index 32.2(8.5) kg/m2; time between COVID-19 onset and CPET 13(7) months; forced expiratory volume in 1 second 89(15) %pred; forced vital capacity 92(14) %pred; diffusing capacity of the lungs for carbon monoxide 92(15) %pred; total lung capacity 86(12) %pred] were studied. Prior to any exercise testing, PEM was assessed relative to the past six months using the modified DePaul Symptom Questionnaire (mDSQ) (0-4 symptoms frequency and severity scores). Each performed a two-day CPET protocol; ramp was 10-20 W/min, with the same ramp rate used for the day-1 and day-2 CPET. Peak oxygen uptake, peak work rate, and gas exchange threshold were measured using standard techniques. Ratings of perceived dyspnea and leg effort during cycling were recorded at peak exercise using the modified Borg’s Scale (0-10). One-sample t-tests were used to assess significance of test-retest mean difference. RESULTS: The mDSQ indicated the presence of PEM symptoms in 80% of participants. However, no significant differences between day-1 and day-2 CPET were found in any of the variables assessed. CONCLUSION: The absence of any difference in cardiorespiratory and perceptual responses in 2-day CPET testing, despite patient reported presence of PEM symptoms, suggests that the two-day CPET protocol may not be a valid tool for the diagnosis of PEM in LC patients