Optimal Guidance Laws for Aircraft and Drones along Specified Flight Paths in the Presence of Wind

In this paper the methodology presented earlier, based on the open loop control approach for real time optimal trajectory synthesis for an unmanned aerial vehicle in UAM applications, is extended to trajectory tracking and feedback control. The reference trajectory was synthesized earlier using the kinematic relations the vehicle must satisfy and a disturbance free ideal point mass model in flight. The feedback control laws, synthesized in this paper, seek to track the reference trajectory, in real time. Although the tracking control laws are based on either linear optimal control or Lyapunov's second method, they are used to control the nonlinear dynamics of the vehicle, with disturbances, in real time. Since it is assumed that the dynamics associated with the horizontal and vertical translation are relative fast, the controls associated with pitch attitude can be independently designed, without altering the altitude (but definitely altering the speed) to maintain the pitch attitude and pitch stability. The additional feedback required for controlling the slower pitch attitude dynamics is obtained and the closed loop pitch attitude stability is also demonstrated with an example. Typical examples demonstrate the application of the method, the aircraft trajectory response and stability

Potential conservation of circadian clock proteins in the phylum Nematoda as revealed by bioinformatic searches

Although several circadian rhythms have been described in C. elegans, its molecular clock remains elusive. In this work we employed a novel bioinformatic approach, applying probabilistic methodologies, to search for circadian clock proteins of several of the best studied circadian model organisms of different taxa (Mus musculus, Drosophila melanogaster, Neurospora crassa, Arabidopsis thaliana and Synechoccocus elongatus) in the proteomes of C. elegans and other members of the phylum Nematoda. With this approach we found that the Nematoda contain proteins most related to the core and accessory proteins of the insect and mammalian clocks, which provide new insights into the nematode clock and the evolution of the circadian system.Fil: Romanowski, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFil: Garavaglia, Matías Javier. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Goya, María Eugenia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ghiringhelli, Pablo Daniel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andres. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Timeless Links Replication Termination to Mitotic Kinase Activation

The mechanisms that coordinate the termination of DNA replication with progression through mitosis are not completely understood. The human Timeless protein (Tim) associates with S phase replication checkpoint proteins Claspin and Tipin, and plays an important role in maintaining replication fork stability at physical barriers, like centromeres, telomeres and ribosomal DNA repeats, as well as at termination sites. We show here that human Tim can be isolated in a complex with mitotic entry kinases CDK1, Auroras A and B, and Polo-like kinase (Plk1). Plk1 bound Tim directly and colocalized with Tim at a subset of mitotic structures in M phase. Tim depletion caused multiple mitotic defects, including the loss of sister-chromatid cohesion, loss of mitotic spindle architecture, and a failure to exit mitosis. Tim depletion caused a delay in mitotic kinase activity in vivo and in vitro, as well as a reduction in global histone H3 S10 phosphorylation during G2/M phase. Tim was also required for the recruitment of Plk1 to centromeric DNA and formation of catenated DNA structures at human centromere alpha satellite repeats. Taken together, these findings suggest that Tim coordinates mitotic kinase activation with termination of DNA replication

BRG1 co-localizes with DNA replication factors and is required for efficient replication fork progression

For DNA replication to occur, chromatin must be remodeled. Yet, we know very little about which proteins alter nucleosome occupancy at origins and replication forks and for what aspects of replication they are required. Here, we demonstrate that the BRG1 catalytic subunit of mammalian SWI/SNF-related complexes co-localizes with origin recognition complexes, GINS complexes, and proliferating cell nuclear antigen at sites of DNA replication on extended chromatin fibers. The specific pattern of BRG1 occupancy suggests it does not participate in origin selection but is involved in the firing of origins and the process of replication elongation. This latter function is confirmed by the fact that Brg1 mutant mouse embryos and RNAi knockdown cells exhibit a 50% reduction in replication fork progression rates, which is associated with decreased cell proliferation. This novel function of BRG1 is consistent with its requirement during embryogenesis and its role as a tumor suppressor to maintain genome stability and prevent cancer

Entrainment of the Mammalian Cell Cycle by the Circadian Clock: Modeling Two Coupled Cellular Rhythms

The cell division cycle and the circadian clock represent two major cellular rhythms. These two periodic processes are coupled in multiple ways, given that several molecular components of the cell cycle network are controlled in a circadian manner. For example, in the network of cyclin-dependent kinases (Cdks) that governs progression along the successive phases of the cell cycle, the synthesis of the kinase Wee1, which inhibits the G2/M transition, is enhanced by the complex CLOCK-BMAL1 that plays a central role in the circadian clock network. Another component of the latter network, REV-ERBα, inhibits the synthesis of the Cdk inhibitor p21. Moreover, the synthesis of the oncogene c-Myc, which promotes G1 cyclin synthesis, is repressed by CLOCK-BMAL1. Using detailed computational models for the two networks we investigate the conditions in which the mammalian cell cycle can be entrained by the circadian clock. We show that the cell cycle can be brought to oscillate at a period of 24 h or 48 h when its autonomous period prior to coupling is in an appropriate range. The model indicates that the combination of multiple modes of coupling does not necessarily facilitate entrainment of the cell cycle by the circadian clock. Entrainment can also occur as a result of circadian variations in the level of a growth factor controlling entry into G1. Outside the range of entrainment, the coupling to the circadian clock may lead to disconnected oscillations in the cell cycle and the circadian system, or to complex oscillatory dynamics of the cell cycle in the form of endoreplication, complex periodic oscillations or chaos. The model predicts that the transition from entrainment to 24 h or 48 h might occur when the strength of coupling to the circadian clock or the level of growth factor decrease below critical values

Disrupting Circadian Homeostasis of Sympathetic Signaling Promotes Tumor Development in Mice

and why disruption of circadian rhythm may lead to tumorigenesis. oncogenic potential, leading to tumor development in the same organ systems in wild-type and circadian gene-mutant mice. is a clock-controlled physiological function. The central circadian clock paces extracellular mitogenic signals that drive peripheral clock-controlled expression of key cell cycle and tumor suppressor genes to generate a circadian rhythm in cell proliferation. Frequent disruption of circadian rhythm is an important tumor promoting factor

Post-Covid-19 Irritable Bowel Syndrome

Objectives The long-term consequences of COVID-19 infection on the gastrointestinal tract remain unclear. Here, we aimed to evaluate the prevalence of gastrointestinal symptoms and post-COVID-19 disorders of gut-brain interaction after hospitalisation for SARS-CoV-2 infection. Design GI-COVID-19 is a prospective, multicentre, controlled study. Patients with and without COVID-19 diagnosis were evaluated on hospital admission and after 1, 6 and 12 months post hospitalisation. Gastrointestinal symptoms, anxiety and depression were assessed using validated questionnaires. Results The study included 2183 hospitalised patients. The primary analysis included a total of 883 patients (614 patients with COVID-19 and 269 controls) due to the exclusion of patients with pre-existing gastrointestinal symptoms and/or surgery. At enrolment, gastrointestinal symptoms were more frequent among patients with COVID-19 than in the control group (59.3% vs 39.7%, p < 0.001). At the 12-month follow-up, constipation and hard stools were significantly more prevalent in controls than in patients with COVID-19 (16% vs 9.6%, p=0.019 and 17.7% vs 10.9%, p=0.011, respectively). Compared with controls, patients with COVID-19 reported higher rates of irritable bowel syndrome (IBS) according to Rome IV criteria: 0.5% versus 3.2%, p=0.045. Factors significantly associated with IBS diagnosis included history of allergies, chronic intake of proton pump inhibitors and presence of dyspnoea. At the 6-month follow-up, the rate of patients with COVID-19 fulfilling the criteria for depression was higher than among controls. Conclusion Compared with controls, hospitalised patients with COVID-19 had fewer problems of constipation and hard stools at 12 months after acute infection. Patients with COVID-19 had significantly higher rates of IBS than controls

Psychological and Clinical Factors Mediate Post-COVID-19 Irritable Bowel Syndrome

Background: Exposure to COVID-19 has been shown previously to be associated with a higher risk for irritable bowel syndrome (IBS). This study aimed to better explain this relationship using mediation analysis. Methods: This post hoc analysis of a multicenter cohort study includes 623 patients with and without COVID-19 infection. All participants completed the ROME IV criteria, gastrointestinal symptom rating scale (GSRS), and hospital anxiety and depression scale (HADS) over 1 year. Mediation analysis utilized the PROCESS macro and Baron and Kenny's method for parametric and nonparametric mediating variables, respectively. Key results: The impact of COVID-19 on the development of post-COVID-19 IBS is completely mediated by dyspnea at baseline (adjusted OR = 3.561, p = 0.012), severity of acid regurgitation at 1 month [indirect effect, log-odds metric = 0.090, 95% CI (0.006-0.180)], hunger pains at 1 [indirect effect, log-odds metric = 0.094, 95% CI (0.024-0.178)], and 6 months [indirect effect, log-odds metric = 0.074, 95% CI (0.003-0.150)], depression at 6 [indirect effect, log-odds metric = 0.106, 95% CI (0.009-0.225)] and 12 months [indirect effect, log-odds metric = 0.146, 95% CI (0.016-0.311)] as well as borborygmus [indirect effect, log-odds metric = 0.095, 95% CI (0.009-0.203)], abdominal distention [indirect effect, log-odds metric = 0.162, 95% CI (0.047-0.303)], and increased flatus [indirect effect, log-odds metric = 0.110, 95% CI (0.005-0.234)] at 12 months. Conclusions and inferences: Our findings provide evidence for psychological and clinical mediators between COVID-19 and post-COVID-19 IBS, which may be promising targets for interventions tailored for treating or preventing depression. The presence of specific GI symptoms at COVID-19 onset and their persistence should increase awareness of a potential new onset of IBS diagnosis.

Long-Term Impact of COVID-19 on Disorders of Gut–Brain Interaction: Incidence, Symptom Burden, and Psychological Comorbidities

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has highlighted the potential exacerbation of gastrointestinal symptoms in patients with disorders of gut-brain interaction (DGBIs). However, the distinct symptom trajectories and psychological burden in patients with post-COVID-19 DGBIs compared with patients with pre-existing irritable bowel syndrome (IBS)/functional dyspepsia (FD) and non-DGBI controls remain poorly understood. Objectives: To examine the long-term gastrointestinal symptom progression and psychological comorbidities in patients with post-COVID-19 DGBI, patients with pre-existing IBS/FD and non-DGBI controls. Methods: This post hoc analysis of a prospective multicenter cohort study reviewed patient charts for demographic data and medical history. Participants completed the Gastrointestinal Symptom Rating Scale at four time points: baseline, 1, 6, and 12&nbsp;months, and the Hospital Anxiety and Depression Scale at 6 and 12&nbsp;months. The cohort was divided into three groups: (1) post-COVID-19 DGBIs (2) non-DGBI, and (3) pre-existing IBS/FD, with the post-COVID-19 DGBIs group compared to the latter two control groups. Results: Among 599 eligible patients, 27 (4.5%) were identified as post-COVID-19 DGBI. This group experienced worsening abdominal pain, hunger pain, heartburn, and acid regurgitation, unlike symptom improvement or stability in non-DGBI controls (p&nbsp;&lt;&nbsp;0.001 for all symptoms, except hunger pain, p&nbsp;=&nbsp;0.001). While patients with pre-existing IBS/FD improved in most gastrointestinal symptoms but worsened in constipation and incomplete evacuation, patients with post-COVID-19 DGBI exhibited consistent symptom deterioration across multiple gastrointestinal domains. Anxiety and depression remained unchanged in patients with post-COVID-19 DGBI, contrasting with significant reductions in controls (non-DGBI: p&nbsp;=&nbsp;0.003 and p&nbsp;=&nbsp;0.057; pre-existing IBS/FD: p&nbsp;=&nbsp;0.019 and p&nbsp;=&nbsp;0.007, respectively). Conclusions: COVID-19 infection is associated with the development of newly diagnosed DGBIs and distinct symptom trajectories when compared with patients with pre-existing IBS/FD. Patients with post-COVID-19 DGBI experience progressive gastrointestinal symptom deterioration and persistent psychological distress, underscoring the need for tailored management strategies for this unique subgroup

Applicability of T1-weighted MRI in the assessment of forensic age based on the epiphyseal closure of the humeral head

This work investigates the value of magnetic resonance imaging analysis of proximal epiphyseal fusion in research examining the growth and development of the humerus and its potential utility in establishing forensic age estimation. In this study, 428 proximal humeral epiphyses (patient age, 12-30years) were evaluated with T1-weighted turbo spin echo (T1 TSE) sequences in coronal oblique orientation on shoulder MRI images. A scoring system was created following a combination of the Schmeling and Kellinghaus methods. Spearman's rank correlation analysis revealed a significant positive relationship between age and ossification stage of the proximal humeral epiphysis (all subjects: rho=0.664, p<0.001; males: 0.631, p<0.001; females: rho=0.651, p<0.001). The intra- and inter-observer reliability assessed using Cohen's kappa statistic was =0.898 and =0.828, respectively. The earliest age of epiphysis closure was 17years for females and 18years for males. MRI of the proximal humeral epiphysis can be considered advantageous for forensic age estimation of living individuals in a variety of situations, ranging from monitoring public health to estimating the age of illegal immigrants/asylum seekers, minors engaged in criminal activities, and illegal participants in competitive sports, without the danger of radiation exposure