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To maintain a robust catalog of resident space objects (RSOs), space situational awareness (SSA) mission operators depend on ground- and space-based sensors to repeatedly detect, characterize, and track objects in orbit. Although some space sensors are capable of monitoring large swaths of the sky with wide fields of view (FOVs), others—such as maneuverable optical telescopes, narrow-band imaging radars, or satellite laser-ranging systems—are restricted to relatively narrow FOVs and must slew at a finite rate from object to object during observation. Since there are many objects that a narrow FOV sensor could choose to observe within its field of regard (FOR), it must schedule its pointing direction and duration using some algorithm. This combinatorial optimization problem is known as the sensor-tasking problem. In this paper, we developed a deep reinforcement learning agent to task a space-based narrow-FOV sensor in low Earth orbit (LEO) using the proximal policy optimization algorithm. The sensor’s performance—both as a singular sensor acting alone, but also as a complement to a network of taskable, narrow-FOV ground-based sensors—is compared to the greedy scheduler across several figures of merit, including the cumulative number of RSOs observed and the mean trace of the covariance matrix of all of the observable objects in the scenario. The results of several simulations are presented and discussed. Additionally, the results from an LEO SSA sensor in different orbits are evaluated and discussed, as well as various combinations of space-based sensors.

Yeast Saccharomyces cerevisiae (S. Cerevisiae) is one of the most attractive microbial species used for industrial production of value-added products and is an important model organism to understand the biology of the eukaryotic cells and humans. S. Cerevisiae has different shapes, such as spherical singlets, budded doublets, and clusters, corresponding to phases of the cell cycle, genetic, and environmental factors. The ability to obtain high-purity populations of uniform-shaped S. Cerevisiae cells is of significant importance for a wide range of applications in basic biological research and industrial processes. In this work, we demonstrate shape-based separation and enrichment of S. Cerevisiae using a coflow of viscoelastic and Newtonian fluids in a straight rectangular microchannel. Due to the combined effects of lift inertial and elastic forces, this label-free and continuous separation arises from shape-dependent migration of cells from the Newtonian to the non-Newtonian viscoelastic fluid. The lateral position of S. Cerevisiae cells with varying morphologies is found to be dependent on cell major axis. We also investigate the effects of sheath and sample flow rate, poly(ethylene oxide) (PEO) concentration and channel length on the performance of the viscoelastic microfluidic device for S. Cerevisiae enrichment and separation by shape. Moreover, the separation efficiency, cell extraction yield, and cell viability after sorting operations are studied.

Yeast

Statins possess anti-inflammatory properties and have a protective effect in certain inflammatory conditions; however, their effect on the natural history of pancreatitis is unknown.The aim of this study is to assess the effect of statin exposure on the severity of pancreatitis and incidence of organ failure using a propensity-matched approach.A historical cohort study was conducted of adult patients with acute pancreatitis (AP) admitted in the Cleveland Clinic Health System between 2007 and 2014. All medication, clinical, and outcomes data were extracted from the electronic medical record. Factors that influence statin use were included in a propensity model to minimize selection bias. Patients on and off statins were matched (1:1) based on the propensity score to simulate a randomized controlled trial. Measured outcomes included pancreatitis severity (Revised Atlanta Classification), incidence of multisystem organ failure (MSOF), new MSOF, acute necrosis, and death. Additional surrogate markers of severity included hospital length of stay, Bedside Index of Severity of Acute Pancreatitis (BISAP), and presence of SIRS.A total of 110 subjects taking a statin at admission were matched with 210 subjects not on a statin. Known baseline factors that may influence statin use and severity of pancreatitis were evenly matched between the 2 groups. Patients on a statin were less likely to develop MSOF, severe AP and necrosis. Although less in-hospital death occurred in the statin group when compared to nonusers, the difference was not statistically significant (2% vs. 4%; P=0.38).Statin use is associated with decreased severity of AP observed as reduction in both overall MSOF incidence and new MSOF. Prospective randomized controlled trials are needed to determine the efficacy of statin drugs in the treatment of AP.

Exposures to cocaine and morphine produce similar adaptations in nucleus accumbens (NAc)-based behaviors, yet produce very different adaptations at NAc excitatory synapses. In an effort to explain this paradox, we found that both drugs induced NMDA receptor-containing, AMPA receptor-silent excitatory synapses, albeit in distinct cell types through opposing cellular mechanisms. Cocaine selectively induced silent synapses in D1-type neurons, likely via a synaptogenesis process, whereas morphine induced silent synapses in D2-type neurons via internalization of AMPA receptors from pre-existing synapses. After drug withdrawal, cocaine-generated silent synapses became 'unsilenced' by recruiting AMPA receptors to strengthen excitatory inputs to D1-type neurons, whereas morphine-generated silent synapses were likely eliminated to weaken excitatory inputs to D2-type neurons. Thus, these cell type-specific, opposing mechanisms produced the same net shift of the balance between excitatory inputs to D1- and D2-type NAc neurons, which may underlie certain common alterations in NAc-based behaviors induced by both classes of drugs.

Objective. To determine if Staphylococcus aureus stimulates the L-arginine‐nitric oxide (NO) synthase pathway in articular cartilage. Methods. A heat-killed and sonicated (denatured) S aureus preparation was added to cultures of bovine articular cartilage. NO production was measured as accumulated nitrite in the culture medium and by the NO synthase‐dependent conversion of 3 H‐L-arginine to 3 H‐L-citrulline in cartilage homogenates. Inducible NO synthase (iNOS) messenger RNA (mRNA) expression was analyzed by Northern blot. Proteoglycan synthesis was measured by 35 SO4 incorporation into glycosaminoglycan. Results. Nitrite accumulation and 3 H‐L-citrulline formation in cartilage were elevated by denatured S aureus (compared with unstimulated control cartilage) and inhibited by the NO synthase inhibitor N G monomethyl-L-arginine. Northern blot analysis revealed increased iNOS mRNA expression in bovine chondrocytes in response to denatured S aureus stimulation. Denatured S aureus suppressed the accumulation of 35 SO4-labeled macromolecules representing newly synthesized proteoglycans in bovine articular cartilage. The suppressed proteoglycan synthesis was due to the presence of NO. Conclusion. These findings support the hypothesis that a component of S aureus can stimulate iNOS in articular cartilage, and that NO generated from this enzyme down-regulates cartilage matrix proteoglycan synthesis.

The effects of motion, or lack of it, on Achilles tendon healing are not well defined. We have recently shown that immobilization has a detrimental effect on tendon healing in a rat model. The aim of this experiment was to determine whether enforced exercise had an additional beneficial effect on the mechanical and functional recovery of divided Achilles tendons in rats. Male Sprague-Dawley rats were randomly allocated into a nonexercise and an exercise group (N = 10 for each group). In both groups the right Achilles tendon was surgically transected. The left, uninjured lower limb served as an internal control. Both groups of animals were housed under identical conditions with the exception that the exercise group swam for 15 minutes per day. Functional performance was determined from the measurement of hindpaw prints of walking rats preoperatively and on alternate postoperative days. On day 15, the animals were killed and weighed, and biomechanical evaluations were performed on both the injured and uninjured Achilles tendon constructs. There were no differences in weight at time of death. All animals had an initial functional deficit that returned to near-normal by day 15. There were significant differences in the morphological and the mechanical properties of the healing Achilles tendon constructs at day 15 when comparing the injured with the uninjured Achilles tendon constructs. Supplemental exercise, however, had no effect on the functional or mechanical recovery of injured or uninjured Achilles tendons in the rat model.

Nitric oxide is a small molecule that is synthesized by a family of enzymes, the nitric oxide synthases, and is overproduced in rheumatoid arthritis and osteoarthrosis. The aim of this investigation was to elucidate the potential sources of nitric oxide in joint tissues and to determine if the production of nitric oxide could be inhibited by dexamethasone or methotrexate, two agents that inhibit other forms of inducible nitric oxide synthase. Methotrexate inhibits the synthesis of biopterin, which is a co-factor for nitric oxide synthase. Explants of human and bovine cartilage and cultured chondrocytes released large amounts of nitrite, the stable end product of nitric oxide, when stimulated with endotoxin, interleukin-1β, or tumor necrosis factor-α. The production of nitrite was time-dependent and endotoxin, interleukin-1β, and tumor necrosis factor-α dose-dependent and was inhibited by the nitric-oxide-synthase inhibitors Nω-nitro-L-arginine methyl ester and aminoguanidine. The inducible nitric oxide synthase in bovine chondrocytes was calcium-dependent and was inhibited by high concentrations of methotrexate or dexamethasone. No constitutive nitric-oxide-synthase activity and little or no inducible nitric-oxide-synthase activity were demonstrable in explants or cell cultures derived from menisci. Fresh explants of bovine articular synovial tissue constitutively released nitrite that was inhibited by Nω-nitro-L-arginine methyl ester, but the release could not be enhanced by endotoxin, interleukin-1β, or tumor necrosis factor-α. There was no constitutive or inducible production of nitrite by explants or cells derived from the synovial tissue or shoulder capsule of a human or by explants or cells derived from canine anterior cruciate, posterior cruciate, medial collateral, lateral collateral, or patellar ligaments. Taken together, these results indicate that chondrocytes represent the major source of inducible nitric oxide synthase and nitric oxide during inflammation or infection of a joint. CLINICAL RELEVANCE : Since nitric oxide is a free radical, its effects are extremely rapid, local, and potentially toxic. Induction of high levels of chondrocytic nitric oxide during infection or inflammation may be responsible in part for the damage to cartilage that occurs in some inflammatory arthropathies. Agents that inhibit nitric oxide synthase, especially selective inhibitors of the inducible form of nitric oxide synthase, may offer new and useful means of inhibiting the destruction of cartilage.

Biometrics, such as fingerprint, iris scan, and face recognition, offer methods for identifying individuals based on a unique physiological measurement. Recent studies indicate that a person's electrocardiogram (ECG) may also provide a unique biometric signature. Several methods for processing ECG data have appeared in the literature and most approaches rest on an initial detection and segmentation of the heartbeats. Various sources of noise, such as sensor noise, poor sensor placement, or muscle movements, can degrade the ECG signal and introduce errors into the heartbeat segmentation. This paper presents a screening technique for assessing the quality of each segmented heartbeat. Using this technique, a higher quality signal can be extracted to support the identification task. We demonstrate the benefits of this quality screening using a principal component technique known as eigenpulse. The analysis demonstrated the improvement in performance attributable to the quality screening.

Nitric oxide’s (NO) involvement in arthritis was first demonstrated when levels of nitrite, a stable endproduct of NO metabolism, were shown to be elevated in serum and synovial fluid samples of rheumatoid and osteoarthritis patients. NO production by chondrocytes, its involvement in various biochemical events of cartilage metabolism, and the in vivo suppression of experimental arthritis by NO synthase inhibitors further implicated NO in arthritis. However, a conclusive role for NO in the pathogenesis of arthritis remains to be defined, in contrast to the NO-cGMP signal transduction pathway of endothelium-mediated vasodilation. It appears that NO has limited modulating effects in cartilage metabolism, with evidence for both protective and deleterious effects. Recent developments that contribute to our understanding of NO’s role in arthritis are discussed.

Nitric oxide (NO . ) is a multifunctional messenger molecule generated by a family of enzymes, the nitric oxide synthases, and is overproduced in osteoarthritis and rheumatoid arthritis. Chondrocytes are the major native source of NO . in diarthrodial joints. Chondrocytic inducible nitric oxide synthase induced by inflammatory cytokines and bacterial cell wall fragments mediates many of the catabolic events in arthritis. Agents which specifically inhibit chondrocyte inducible NO . synthase, may thus have a role in the management in arthritis. We evaluated a novel class of potential inducible NO . synthase inhibitors, the S -substituted isothioureas, for their ability to inhibit inducible NO . synthase activity in cultured bovine chondrocytes and explants of cartilage from patients with osteoarthritis. Two isothioureas, S -methyl isothiourea and S -(aminoethyl) isothiourea were 2–4 times more potent than N G -monomethyl- l -arginine monoacetate, 5–10 times more potent than aminoguanidine and over 300 times more potent than N ω -nitro- l -arginine and N ω -nitro- l -arginine methyl ester. The rank order of potency of the NO . synthase inhibitors was S -(aminoethyl) isothiourea> S -methyl isothiourea > N G -monomethyl- l -arginine > aminoguanidine > N ω -nitro- l -arginine = N ω -nitro- l -arginine methyl ester. The order of potency was reversed ( N ω -nitro- l -arginine methyl ester = N ω -nitro- l -arginine > N G -monomethyl- l -arginine = S -methyl isothiourea> S -(aminoethyl) isothiourea>aminoguanidine) when evaluating the same compounds ability to inhibit constitutive NO . synthase activity in bovine endothelial cells. In comparison to conventional arginine-based analogs, the isothioureas represent a more potent and relatively specific class of inhibitors of inducible NO . synthase in cartilage and thus may be beneficial in the management of arthritis.

Methods: 32 rats were randomised into: (1) sham operated (sldn incision only), (2) division only (surgical transection of the Achilles tendon), (3) "dummy" ex-fix (Achilles tendon division and K-wires through the femur, proximal tibia, calcaneus and metatarsals), (4) rigid exf i x (K-wires fixed by two triangular frames). 20 rats were randomised into: ( 1 ) normal cage activity group, (2) exercise group (15 min/day swimming). Functional recovery was evaluated in an objective blinded fashion from hind paw prints (the Achilles Functional Index: AFI). The mechanical properties of the healing Achilles tendon constructs were evaluated on day 15.

V-79 Chinese hamster cells grown as monolayers or as multicell spheroids were treated with Photofrin II (10 μ.g m−1 for 16 h) and various doses of red light irradiation. The resulting biochemical and functional damage to cell mitochondria was studied. The activities of both succinic dehydrogenese and cytochrome c oxidase were found to decrease in a light dose-dependent manner. The respiratory control quotient (RC) decreased in parallel with a decrease in the activities of the respiratory chain proteins. Our data also showed a distinct temporal difference in the relative progression of mitochondrial damage and cell death as assessed by loss of discrete Rhodamine-123 (Rh-123) localization and trypan blue infiltration, respectively. Mitochondrial damage was detected immediately, as seen by derealization of Rh-123 resulting from dissipation of the electrochemical gradient in damaged mitochondria. Trypan blue infiltration occurs with a distinct time lag. These findings are consistent with the hypothesis that, at least for long Photofrin II incubation times, the mitochondrion is a primary target of photosensitization. The subsequent changes in cell membrane permeability may be a delayed result of decreased bioenergetics of the Photofrin II photosensitized cell.

The role of the messenger molecule nitric oxide has not been evaluated in fracture healing. NO is synthesized by three kinds of nitric oxide synthase (NOS): inducible NOS (iNOS), endothelial (eNOS), and neuronal (bNOS). We evaluated the role of these enzymes in a rat femur fracture-healing model. There was no messenger RNA (mRNA) expression, immunoreactivity, or enzymatic activity for NOS in unfractured femoral cortex. After fracture, however, mRNA, protein, and enzymatic activity for iNOS were identified in the healing rat femoral fracture callus, with maximum activity on day 15. The mRNA expression for eNOS and bNOS was induced slightly later than for iNOS, consistent with a temporal increase in calcium-dependent NOS activity that gradually increased up to day 30. mRNA expression for the three NOS isoforms also was found in six of six human fracture callus samples. To study the effect of suppression of NO synthesis on fracture healing, an experimental group of rats was fed an NOS inhibitor, L-nitroso-arginine methyl ester (L-NAME), and the control group was fed its inactive enantiomer, D-nitroso-arginine methyl ester (D-NAME). An 18% (p < or = 0.01) decrease in cross-sectional area and a 45% (p < or = 0.05) decrease in failure load were observed in the NOS-inhibited group on day 24 after fracture. Furthermore, the effect of NO supplementation to fracture healing was studied by delivering NO to the fracture site using carboxybutyl chitosan NONOate locally. On day 17 after fracture, there was a 30% (p < or = 0.05) increase in cross-sectional area in the NO-donor group compared with the NOS inhibition group. These results show for the first time that NO is expressed during fracture healing in rats and in humans, that suppression of NOS impairs fracture healing, and that supplementation of NO can reverse the inhibition of healing produced by NOS inhibitors.