Joint probabilistic data association and smoothing applied to multiple space object tracking

A foundational aspect of space domain awareness is the ability to identify and track space objects, including space object discovery and custody. This paper demonstrates the power of combining an efficient multiple hypothesis joint probabilistic data association (MH-JPDA) algorithm with a fixed-interval smoother to simultaneously track multiple space objects. For newly discovered objects, statistical initial orbit determination (SIOD) is possible with a single short optical tracklet, but results in large initial uncertainties. Combining these uncertainties with closely spaced objects can result in highly ambiguous data associations, which can lead to poor state estimates and even filter divergence. This paper invokes MH-JPDA to probabilistically update multiple tracks with multiple simultaneous observations in a sequential filter, while avoiding assigning one-to-one associations. Once sufficient information has been collected, the space objects become uniquely distinguishable among each other. Subsequently, the smoother is applied to achieve improved association of the prior observations. MH-JPDA allows for immediate track formation (using SIOD) and sequential processing of incoming observations, providing statistically rigorous real-time state estimates, whereas smoothing produces a more-refined, higher-confidence overall track estimate at user-defined intervals. This paper demonstrates this approach within the Constrained Admissible Region, Multiple Hypothesis Filter (CAR-MHF) software by tracking a simulated break-up scenario.Jason Stauch, Travis Bessell, Mark Rutten, Jason Baldwin, Moriba Jah and Keric Hil

Health-seeking behaviour, diagnostics and transmission dynamics in the control of visceral leishmaniasis in the Indian subcontinent.

Countries in the Indian subcontinent have committed to reducing the incidence of kala-azar, a clinical manifestation of visceral leishmaniasis, to below 1 in 10,000 by 2020. We address the role of timing of use and accuracy of diagnostics in kala-azar control and elimination. We use empirical data on health-seeking behaviour and health-system performance from the Indian state of Bihar, Bangladesh and Nepal to parameterize a mathematical model. Diagnosis of cases is key to case management, control and surveillance. Treatment of cases prevents onward transmission, and we show that the differences in time to diagnosis in these three settings explain the observed differences in incidence. Shortening the time from health-care seeking to diagnosis is likely to lead to dramatic reductions in incidence in Bihar, bringing the incidence down to the levels seen in Bangladesh and Nepal. The results emphasize the importance of maintaining population and health-system awareness, particularly as transmission and disease incidence decline. We explore the possibility of diagnosing patients before the onset of clinical kala-azar (before 14 days fever), and show that this could have a marked impact on incidence, even for a moderately sensitive test. However, limited specificity (that results in false positives) is a major barrier to such a strategy. Diagnostic tests of high specificity used at an early stage of active infection, even if sensitivity is only moderate, could have a key role in the control of kala-azar, and prevent its resurgence when paired with the passive health-care system and tests of high sensitivity, such as the test for rK39 antibody response

Elimination of visceral leishmaniasis in the Indian subcontinent: a comparison of predictions from three transmission models.

We present three transmission models of visceral leishmaniasis (VL) in the Indian subcontinent (ISC) with structural differences regarding the disease stage that provides the main contribution to transmission, including models with a prominent role of asymptomatic infection, and fit them to recent case data from 8 endemic districts in Bihar, India. Following a geographical cross-validation of the models, we compare their predictions for achieving the WHO VL elimination targets with ongoing treatment and vector control strategies. All the transmission models suggest that the WHO elimination target (<1 new VL case per 10,000 capita per year at sub-district level) is likely to be met in Bihar, India, before or close to 2020 in sub-districts with a pre-control incidence of 10 VL cases per 10,000 people per year or less, when current intervention levels (60% coverage of indoor residual spraying (IRS) of insecticide and a delay of 40days from onset of symptoms to treatment (OT)) are maintained, given the accuracy and generalizability of the existing data regarding incidence and IRS coverage. In settings with a pre-control endemicity level of 5/10,000, increasing the effective IRS coverage from 60 to 80% is predicted to lead to elimination of VL 1-3 years earlier (depending on the particular model), and decreasing OT from 40 to 20days to bring elimination forward by approximately 1year. However, in all instances the models suggest that L. donovani transmission will continue after 2020 and thus that surveillance and control measures need to remain in place until the longer-term aim of breaking transmission is achieved

Nine weeks of supplementation with a multi-nutrient product augments gains in lean mass, strength, and muscular performance in resistance trained men

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to compare the effects of supplementation with Gaspari Nutrition's SOmaxP Maximum Performance™ (SOmaxP) versus a comparator product (CP) containing an equal amount of creatine (4 g), carbohydrate (39 g maltodextrin), and protein (7 g whey protein hydrolysate) on muscular strength, muscular endurance, and body composition during nine weeks of intense resistance training.</p> <p>Methods</p> <p>Using a prospective, randomized, double-blind design, 20 healthy men (mean ± SD age, height, weight, % body fat: 22.9 ± 2.6 y, 178.4 ± 5.7 cm, 80.5 ± 6.6 kg, 16.6 ± 4.0%) were matched for age, body weight, resistance training history, bench press strength, bench press endurance, and percent body fat and then randomly assigned via the ABBA procedure to ingest 1/2 scoop (dissolved in 15 oz water) of SOmaxP or CP prior to, and another 1/2 scoop (dissolved in 15 oz water) during resistance exercise. Body composition (DEXA), muscular performance (1-RM bench press and repetitions to failure [RTF: 3 sets × baseline body weight, 60-sec rest between sets]), and clinical blood chemistries were measured at baseline and after nine weeks of supplementation and training. Subjects were required to maintain their normal dietary habits and follow a specific, progressive overload resistance training program (4-days/wk, upper body/lower body split) during the study. An intent-to-treat approach was used and data were analyzed via ANCOVA using baseline values as the covariate. Statistical significance was set <it>a priori </it>at p ≤ 0.05.</p> <p>Results</p> <p>When adjusted for initial differences, significant between group post-test means were noted in: 1-RM bench press (SOmaxP: 133.3 ± 1.3 kg [19.8% increase] vs. CP: 128.5 ± 1.3 kg [15.3% increase]; p < 0.019); lean mass (SOmaxP: 64.1 ± 0.4 kg [2.4% increase] vs. 62.8 ± 0.4 kg [0.27% increase], p < 0.049); RTF (SOmaxP: 33.3 ± 1.1 reps [44.8% increase] vs. 27.8 ± 1.1 reps [20.9% increase], p < 0.004); and fat mass (SOmaxP: 12.06 ± 0.53 kg [9.8% decrease] vs. 13.90 ± 0.53 kg [4.1% increase], p < 0.024). No statistically significant differences in vital signs (heart rate, systolic and diastolic blood pressures) or clinical blood chemistries were noted.</p> <p>Conclusions</p> <p>These data indicate that compared to CP, SOmaxP administration augments and increases gains in lean mass, bench press strength, and muscular performance during nine weeks of intense resistance training. Studies designed to confirm these results and clarify the molecular mechanisms by which SOmaxP exerts the observed salutary effects have begun. Both SOmaxP and the CP were well-tolerated, and no supplement safety issues were identified.</p

Virtual discovery of melatonin receptor ligands to modulate circadian rhythms

The neuromodulator melatonin synchronizes circadian rhythms and related physiological functions through the actions of two G-protein-coupled receptors: MT1 and MT2. Circadian release of melatonin at night from the pineal gland activates melatonin receptors in the suprachiasmatic nucleus of the hypothalamus, synchronizing the physiology and behaviour of animals to the light–dark cycle1–4. The two receptors are established drug targets for aligning circadian phase to this cycle in disorders of sleep5,6 and depression1–4,7–9. Despite their importance, few in vivo active MT1-selective ligands have been reported2,8,10–12, hampering both the understanding of circadian biology and the development of targeted therapeutics. Here we docked more than 150 million virtual molecules to an MT1 crystal structure, prioritizing structural fit and chemical novelty. Of these compounds, 38 high-ranking molecules were synthesized and tested, revealing ligands with potencies ranging from 470 picomolar to 6 micromolar. Structure-based optimization led to two selective MT1 inverse agonists—which were topologically unrelated to previously explored chemotypes—that acted as inverse agonists in a mouse model of circadian re-entrainment. Notably, we found that these MT1-selective inverse agonists advanced the phase of the mouse circadian clock by 1.3–1.5 h when given at subjective dusk, an agonist-like effect that was eliminated in MT1- but not in MT2-knockout mice. This study illustrates the opportunities for modulating melatonin receptor biology through MT1-selective ligands and for the discovery of previously undescribed, in vivo active chemotypes from structure-based screens of diverse, ultralarge libraries. © 2020, The Author(s), under exclusive licence to Springer Nature Limited

Комплексна система захисту інформації відділу розробки сільськогосподарської техніки ТОВ «Промислова Група «Корсунь»

Брижата Н. Ю. Комплексна система захисту інформації відділу розробки сільськогосподарської техніки ТОВ «Промислова Група «Корсунь» : кваліфікаційна робота бакалавра / Брижата Наталія Юріївна. – Дніпро, 2020. – 92 с.В кваліфікаційній роботі виконана розробка КСЗІ. Наведено загальні відомості про об’єкт інформаційної діяльності. Проведено обстеження об’єкту інформаційної діяльності, категоріювання інформаційно-телекомунікаційної системи, обрано профіль захищеності. Визначені основні загрози

Loss of Prolyl Hydroxylase-1 Protects Against Colitis Through Reduced Epithelial Cell Apoptosis and Increased Barrier Function

Background &amp; Aims Hypoxia inducible factor (HIF) prolyl hydroxylase inhibitors are protective in mouse models of inflammatory bowel disease (IBD). Here, we investigated the therapeutic target(s) and mechanism(s) involved. Methods The effect of genetic deletion of individual HIF-prolyl hydroxylase (PHD) enzymes on the development of dextran sulphate sodium (DSS)induced colitis was examined in mice. Results PHD1-/-, but not PHD2+/- or PHD3-/-, mice were less susceptible to the development of colitis than wild-type controls as determined by weight loss, disease activity, colon histology, neutrophil infiltration, and cytokine expression. Reduced susceptibility of PHD1-/- mice to colitis was associated with increased density of colonic epithelial cells relative to wild-type controls, which was because of decreased levels of apoptosis that resulted in enhanced epithelial barrier function. Furthermore, with the use of cultured epithelial cells it was confirmed that hydroxylase inhibition reversed DSS-induced apoptosis and barrier dysfunction. Finally, PHD1 levels were increased with disease severity in intestinal tissue from patients with IBD and in colonic tissues from DSS-treated mice. Conclusions These results imply a role for PHD1 as a positive regulator of intestinal epithelial cell apoptosis in the inflamed colon. Genetic loss of PHD1 is protective against colitis through decreased epithelial cell apoptosis and consequent enhancement of intestinal epithelial barrier function. Thus, targeted PHD1 inhibition may represent a new therapeutic approach in IBD. © 2010 AGA Institute

Argyrin B a non-competitive inhibitor of the human immunoproteasome exhibiting preference for β1i

Inhibitors of the proteasome have found broad therapeutic applications however, they show severe toxicity due to the abundance of proteasomes in healthy cells. In contrast, inhibitors of the immunoproteasome, which is upregulated during disease states, are less toxic and have increased therapeutic potential including against autoimmune disorders. In this project, we report argyrin B, a natural product cyclic peptide to be a reversible, non-competitive inhibitor of the immunoproteasome. Argyrin B showed selective inhibition of the β5i and β1i sites of the immunoproteasome over the β5c and β1c sites of the constitutive proteasome with nearly 20-fold selective inhibition of β1i over the homologous β1c. Molecular modelling attributes the β1i over β1c selectivity to the small hydrophobic S1 pocket of β1i and β5i over β5c to site-specific amino acid variations that enable additional bonding interactions and stabilization of the binding conformation. These findings facilitate the design of immunoproteasome selective and reversible inhibitors that may have a greater therapeutic potential and lower toxicity

Late pleistocene sedimentation history of the Shirshov Ridge, Bering Sea

The analysis of the lithology, grain-size distribution, clay minerals, and geochemistry of Upper Pleistocene sediments from the submarine Shirshov Ridge (Bering Sea) showed that the main source area was the Yukon–Tanana terrane of Central Alaska. The sedimentary materials were transported by the Yukon River through Beringia up to the shelf break, where they were entrained by a strong northwestward-flowing sea current. The lithological data revealed several pulses of ice-rafted debris deposition, roughly synchronous with Heinrich events, and periods of weaker bottom-current intensity. Based on the geochemical results, we distinguished intervals of an increase in paleoproductivity and extension of the oxygen minimum zone. The results suggest that there were three stages of deposition driven by glacioeustatic sea-level fluctuations and glacial cycles in Alaska