On Stabilization of Cart-Inverted Pendulum System: An Experimental Study

The Cart-Inverted Pendulum System (CIPS) is a classical benchmark control problem. Its dynamics resembles with that of many real world systems of interest like missile launchers, pendubots, human walking and segways and many more. The control of this system is challenging as it is highly unstable, highly non-linear, non-minimum phase system and underactuated. Further, the physical constraints on the track position control voltage etc. also pose complexity in its control design. The thesis begins with the description of the CIPS together with hardware setup used for research, its dynamics in state space and transfer function models. In the past, a lot of research work has been directed to develop control strategies for CIPS. But, very little work has been done to validate the developed design through experiments. Also robustness margins of the developed methods have not been analysed. Thus, there lies an ample opportunity to develop controllers and study the cart-inverted pendulum controlled system in real-time. The objective of this present work is to stabilize the unstable CIPS within the different physical constraints such as in track length and control voltage. Also, simultaneously ensure good robustness. A systematic iterative method for the state feedback design by choosing weighting matrices key to the Linear Quadratic Regulator (LQR) design is presented. But, this yields oscillations in cart position. The Two-Loop-PID controller yields good robustness, and superior cart responses. A sub-optimal LQR based state feedback subjected to H∞ constraints through Linear Matrix Inequalities (LMIs) is solved and it is observed from the obtained results that a good stabilization result is achieved. Non-linear cart friction is identified using an exponential cart friction and is modeled as a plant matrix uncertainty. It has been observed that modeling the cart friction as above has led to improved cart response. Subsequently an integral sliding mode controller has been designed for the CIPS. From the obtained simulation and experiments it is seen that the ISM yields good robustness towards the output channel gain perturbations. The efficacies of the developed techniques are tested both in simulation and experimentation. It has been also observed that the Two-Loop PID Controller yields overall satisfactory response in terms of superior cart position and robustness. In the event of sensor fault the ISM yields best performance out of all the techniques

Lemaitre-Tolman-Bondi collapse from the perspective of loop quantum gravity

Lemaitre-Tolman-Bondi models as specific spherically symmetric solutions of general relativity simplify in their reduced form some of the mathematical ingredients of black hole or cosmological applications. The conditions imposed in addition to spherical symmetry turn out to take a simple form at the kinematical level of loop quantum gravity, which allows a discussion of their implications at the quantum level. Moreover, the spherically symmetric setting of inhomogeneity illustrates several non-trivial properties of lattice refinements of discrete quantum gravity. Nevertheless, the situation at the dynamical level is quite non-trivial and thus provides insights to the anomaly problem. At an effective level, consistent versions of the dynamics are presented which implement the conditions together with the dynamical constraints of gravity in an anomaly-free manner. These are then used for analytical as well as numerical investigations of the fate of classical singularities, including non-spacelike ones, as they generically develop in these models. None of the corrections used here resolve those singularities by regular effective geometries. However, there are numerical indications that the collapse ends in a tamer shell-crossing singularity prior to the formation of central singularities for mass functions giving a regular conserved mass density. Moreover, we find quantum gravitational obstructions to the existence of exactly homogeneous solutions within this class of models. This indicates that homogeneous models must be seen in a wider context of inhomogeneous solutions and their reduction in order to provide reliable dynamical conclusions.Comment: 56 pages, 42 figure

Pd Nanoparticles and Thin Films for Room Temperature Hydrogen Sensor

We report the application of palladium nanoparticles and thin films for hydrogen sensor. Electrochemically grown palladium particles with spherical shapes deposited on Si substrate and sputter deposited Pd thin films were used to detect hydrogen at room temperature. Grain size dependence of H2sensing behavior has been discussed for both types of Pd films. The electrochemically grown Pd nanoparticles were observed to show better hydrogen sensing response than the sputtered palladium thin films. The demonstration of size dependent room temperature H2sensing paves the ways to fabricate the room temperature metallic and metal–metal oxide semiconductor sensor by tuning the size of metal catalyst in mixed systems. H2sensing by the Pd nanostructures is attributed to the chemical and electronic sensitization mechanisms

A Glial Signature and Wnt7 Signaling Regulate Glioma-Vascular Interactions and Tumor Microenvironment.

Gliomas comprise heterogeneous malignant glial and stromal cells. While blood vessel co-option is a potential mechanism to escape anti-angiogenic therapy, the relevance of glial phenotype in this process is unclear. We show that Olig2+ oligodendrocyte precursor-like glioma cells invade by single-cell vessel co-option and preserve the blood-brain barrier (BBB). Conversely, Olig2-negative glioma cells form dense perivascular collections and promote angiogenesis and BBB breakdown, leading to innate immune cell activation. Experimentally, Olig2 promotes Wnt7b expression, a finding that correlates in human glioma profiling. Targeted Wnt7a/7b deletion or pharmacologic Wnt inhibition blocks Olig2+ glioma single-cell vessel co-option and enhances responses to temozolomide. Finally, Olig2 and Wnt7 become upregulated after anti-VEGF treatment in preclinical models and patients. Thus, glial-encoded pathways regulate distinct glioma-vascular microenvironmental interactions

Social contact patterns and implications for infectious disease transmission: a systematic review and meta-analysis of contact surveys

Background: Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focussed on high-income settings. Methods: Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys we explored how contact characteristics (number, location, duration and whether physical) vary across income settings. Results: Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age-groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, but low-income settings were characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income-strata on the frequency, duration and type of contacts individuals made. Conclusions: These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens, as well as the effectiveness of different non-pharmaceutical interventions

A Cross-Species Analysis of a Mouse Model of Breast Cancer-Specific Osteolysis and Human Bone Metastases Using Gene Expression Profiling

<p>Abstract</p> <p>Background</p> <p>Breast cancer is the second leading cause of cancer-related death in women in the United States. During the advanced stages of disease, many breast cancer patients suffer from bone metastasis. These metastases are predominantly osteolytic and develop when tumor cells interact with bone. <it>In vivo </it>models that mimic the breast cancer-specific osteolytic bone microenvironment are limited. Previously, we developed a mouse model of tumor-bone interaction in which three mouse breast cancer cell lines were implanted onto the calvaria. Analysis of tumors from this model revealed that they exhibited strong bone resorption, induction of osteoclasts and intracranial penetration at the tumor bone (TB)-interface.</p> <p>Methods</p> <p>In this study, we identified and used a TB microenvironment-specific gene expression signature from this model to extend our understanding of the metastatic bone microenvironment in human disease and to predict potential therapeutic targets.</p> <p>Results</p> <p>We identified a TB signature consisting of 934 genes that were commonly (among our 3 cell lines) and specifically (as compared to tumor-alone area within the bone microenvironment) up- and down-regulated >2-fold at the TB interface in our mouse osteolytic model. By comparing the TB signature with gene expression profiles from human breast metastases and an <it>in vitro </it>osteoclast model, we demonstrate that our model mimics both the human breast cancer bone microenvironment and osteoclastogenesis. Furthermore, we observed enrichment in various signaling pathways specific to the TB interface; that is, TGF-β and myeloid self-renewal pathways were activated and the Wnt pathway was inactivated. Lastly, we used the TB-signature to predict cyclopenthiazide as a potential inhibitor of the TB interface.</p> <p>Conclusion</p> <p>Our mouse breast cancer model morphologically and genetically resembles the osteoclastic bone microenvironment observed in human disease. Characterization of the gene expression signature specific to the TB interface in our model revealed signaling mechanisms operative in human breast cancer metastases and predicted a therapeutic inhibitor of cancer-mediated osteolysis.</p

Global burden of respiratory infections associated with seasonal influenza in children under 5 years in 2018: a systematic review and modelling study

Background: Seasonal influenza virus is a common cause of acute lower respiratory infection (ALRI) in young children. In 2008, we estimated that 20 million influenza-virus-associated ALRI and 1 million influenza-virus-associated severe ALRI occurred in children under 5 years globally. Despite this substantial burden, only a few low-income and middle-income countries have adopted routine influenza vaccination policies for children and, where present, these have achieved only low or unknown levels of vaccine uptake. Moreover, the influenza burden might have changed due to the emergence and circulation of influenza A/H1N1pdm09. We aimed to incorporate new data to update estimates of the global number of cases, hospital admissions, and mortality from influenza-virus-associated respiratory infections in children under 5 years in 2018. Methods: We estimated the regional and global burden of influenza-associated respiratory infections in children under 5 years from a systematic review of 100 studies published between Jan 1, 1995, and Dec 31, 2018, and a further 57 high-quality unpublished studies. We adapted the Newcastle-Ottawa Scale to assess the risk of bias. We estimated incidence and hospitalisation rates of influenza-virus-associated respiratory infections by severity, case ascertainment, region, and age. We estimated in-hospital deaths from influenza virus ALRI by combining hospital admissions and in-hospital case-fatality ratios of influenza virus ALRI. We estimated the upper bound of influenza virus-associated ALRI deaths based on the number of in-hospital deaths, US paediatric influenza-associated death data, and population-based childhood all-cause pneumonia mortality data in six sites in low-income and lower-middle-income countries. Findings: In 2018, among children under 5 years globally, there were an estimated 109·5 million influenza virus episodes (uncertainty range [UR] 63·1–190·6), 10·1 million influenza-virus-associated ALRI cases (6·8–15·1); 870 000 influenza-virus-associated ALRI hospital admissions (543 000–1 415 000), 15 300 in-hospital deaths (5800–43 800), and up to 34 800 (13 200–97 200) overall influenza-virus-associated ALRI deaths. Influenza virus accounted for 7% of ALRI cases, 5% of ALRI hospital admissions, and 4% of ALRI deaths in children under 5 years. About 23% of the hospital admissions and 36% of the in-hospital deaths were in infants under 6 months. About 82% of the in-hospital deaths occurred in low-income and lower-middle-income countries. Interpretation: A large proportion of the influenza-associated burden occurs among young infants and in low-income and lower middle-income countries. Our findings provide new and important evidence for maternal and paediatric influenza immunisation, and should inform future immunisation policy particularly in low-income and middle-income countries. Funding: WHO; Bill & Melinda Gates Foundation.Fil: Wang, Xin. University of Edinburgh; Reino UnidoFil: Li, You. University of Edinburgh; Reino UnidoFil: O'Brien, Katherine L.. University Johns Hopkins; Estados UnidosFil: Madhi, Shabir A.. University of the Witwatersrand; SudáfricaFil: Widdowson, Marc Alain. Centers for Disease Control and Prevention; Estados UnidosFil: Byass, Peter. Umea University; SueciaFil: Omer, Saad B.. Yale School Of Public Health; Estados UnidosFil: Abbas, Qalab. Aga Khan University; PakistánFil: Ali, Asad. Aga Khan University; PakistánFil: Amu, Alberta. Dodowa Health Research Centre; GhanaFil: Azziz-Baumgartner, Eduardo. Centers for Disease Control and Prevention; Estados UnidosFil: Bassat, Quique. University Of Barcelona; EspañaFil: Abdullah Brooks, W.. University Johns Hopkins; Estados UnidosFil: Chaves, Sandra S.. Centers for Disease Control and Prevention; Estados UnidosFil: Chung, Alexandria. University of Edinburgh; Reino UnidoFil: Cohen, Cheryl. National Institute For Communicable Diseases; SudáfricaFil: Echavarría, Marcela Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Fasce, Rodrigo A.. Public Health Institute; ChileFil: Gentile, Angela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Gordon, Aubree. University of Michigan; Estados UnidosFil: Groome, Michelle. University of the Witwatersrand; SudáfricaFil: Heikkinen, Terho. University Of Turku; FinlandiaFil: Hirve, Siddhivinayak. Kem Hospital Research Centre; IndiaFil: Jara, Jorge H.. Universidad del Valle de Guatemala; GuatemalaFil: Katz, Mark A.. Clalit Research Institute; IsraelFil: Khuri Bulos, Najwa. University Of Jordan School Of Medicine; JordaniaFil: Krishnan, Anand. All India Institute Of Medical Sciences; IndiaFil: de Leon, Oscar. Universidad del Valle de Guatemala; GuatemalaFil: Lucero, Marilla G.. Research Institute For Tropical Medicine; FilipinasFil: McCracken, John P.. Universidad del Valle de Guatemala; GuatemalaFil: Mira-Iglesias, Ainara. Fundación Para El Fomento de la Investigación Sanitaria; EspañaFil: Moïsi, Jennifer C.. Agence de Médecine Préventive; FranciaFil: Munywoki, Patrick K.. No especifíca;Fil: Ourohiré, Millogo. No especifíca;Fil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Rahi, Manveer. University of Edinburgh; Reino UnidoFil: Rasmussen, Zeba A.. National Institutes Of Health; Estados UnidosFil: Rath, Barbara A.. Vienna Vaccine Safety Initiative; AlemaniaFil: Saha, Samir K.. Child Health Research Foundation; BangladeshFil: Simões, Eric A.F.. University of Colorado; Estados UnidosFil: Sotomayor, Viviana. Ministerio de Salud de Santiago de Chile; ChileFil: Thamthitiwat, Somsak. Thailand Ministry Of Public Health; TailandiaFil: Treurnicht, Florette K.. University of the Witwatersrand; SudáfricaFil: Wamukoya, Marylene. African Population & Health Research Center; KeniaFil: Lay-Myint, Yoshida. Nagasaki University; JapónFil: Zar, Heather J.. University of Cape Town; SudáfricaFil: Campbell, Harry. University of Edinburgh; Reino UnidoFil: Nair, Harish. University of Edinburgh; Reino Unid

Search for Gravitational-wave Signals Associated with Gamma-Ray Bursts during the Second Observing Run of Advanced LIGO and Advanced Virgo

We present the results of targeted searches for gravitational-wave transients associated with gamma-ray bursts during the second observing run of Advanced LIGO and Advanced Virgo, which took place from 2016 November to 2017 August. We have analyzed 98 gamma-ray bursts using an unmodeled search method that searches for generic transient gravitational waves and 42 with a modeled search method that targets compact-binary mergers as progenitors of short gamma-ray bursts. Both methods clearly detect the previously reported binary merger signal GW170817, with p-values of <9.38 × 10−6 (modeled) and 3.1 × 10−4 (unmodeled). We do not find any significant evidence for gravitational-wave signals associated with the other gamma-ray bursts analyzed, and therefore we report lower bounds on the distance to each of these, assuming various source types and signal morphologies. Using our final modeled search results, short gamma-ray burst observations, and assuming binary neutron star progenitors, we place bounds on the rate of short gamma-ray bursts as a function of redshift for z ≤ 1. We estimate 0.07─1.80 joint detections with Fermi-GBM per year for the 2019─20 LIGO-Virgo observing run and 0.15─3.90 per year when current gravitational-wave detectors are operating at their design sensitivities

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

The impacts of climate change on the winter water cycle of the western Himalaya

Some 180 million people depend on the Indus River as a key water resource, fed largely by precipitation falling over the western Himalaya. However, the projected response of western Himalayan precipitation to climate change is currently not well constrained: CMIP5 GCMs project a reduced frequency and vorticity of synoptic-scale systems impacting the area, but such systems would exist in a considerably moister atmosphere. In this study, a convection-permitting (4 km horizontal resolution) setup of the Weather Research and Forecasting (WRF) model is used to examine 40 cases of these synoptic-scale systems, known as western disturbances (WDs), as they interact with the western Himalaya. In addition to a present-day control run, three experiments are performed by perturbing the boundary and initial conditions to reflect pre-industrial, RCP4.5 and RCP8.5 background climates respectively. It is found that in spite of the weakening intensity of WDs, net precipitation associated with them in future climate scenarios increases significantly; conversely there is no net change in precipitation between the pre-industrial and control experiments despite a significant conversion of snowfall in the pre-industrial experiment to rainfall in the control experiment, consistent with the changes seen in historical observations. This shift from snowfall to rainfall has profound consequences on water resource management in the Indus Valley, where irrigation is dependent on spring meltwater. Flux decomposition shows that the increase in future precipitation follows directly from the projected moistening of the tropical atmosphere (which increases the moisture flux incident on the western Himalaya by 28%) overpowering the weakened dynamics (which decreases it by 20%). Changes to extreme rainfall events are also examined: it is found that such events may increase significantly in frequency in both future scenarios examined. Two-hour maxima rainfall events that currently occur in 1-in-8 WDs are projected to increase tenfold in frequency in the RCP8.5 scenario; more prolonged (one-week maxima) events are projected to increase fiftyfold