PD1(programmed cell death protein 1), a molecule negatively regulated by immunity，is highly expressed in a wide variety of human malignancies making it an attractive immunotherapeutic target. PD-L1 is one of the ligands for PD-1 and expressed both on T cells and tumor cells. The purpose of this study was to investigate the expression levels of PD1, PD-L1, regulatory T cells (Tregs), identified as CD4+CD25+CD127-/low, and related cytokines during the development and progression of cervical cancer(CC). Through different groups to simulate the process of the occurrence and development of CC, peripheral blood of each group was collected, and different indicators were detected by ELISA and flow analysis. It was found that except for INF-γ, PD1, PD-L1, IL-2, IL6, IL-10, TGF-β expression increased gradually with the development of CC, and the differences between groups were statistically significant (P<0.05). This situation also appears on the tracking of preoperative CC patients and postoperative follow-up on test results. And Tregs in peripheral blood, compared with normal control(NC) group, the expression increased CC group, the PD1 expression in the Tregs membrane also increases at the same time. In CC tissues, we found an interesting phenomenon through multiplex immunohistochemical staining that CD8+ T cells mainly infiltrated in the tumor cell aggregation area, while CD4+ T cells mainly appeared around. Therefore, we speculated that CD8+ T cells mainly played an anti-tumor immune role in CC tumor tissues.

O postulado 3Até este ponto de nossa tentativa de axiomatização da mecânica clássica, introduzimos dois postulados: Postulado 1: A posição de uma partícula é representada por um ponto em \(\mathbb{R}^{3}\).Postulado 2: A distância entre duas partículas é definida pela métrica euclidiana.Com estes pontulados, discutimos os conceitos dePartícula e Interação;O espaço euclidiano e suas simetrias;Observáveis euclidianos,como integrantes fundamentais da teoria.Agora, devemos introduzir outros dois postulados. O primeiro sedimenta a ideia de como o movimento das partículas é representado no espaço euclidiano e se suporta na percepção de que uma partícula não pode ser criada ou destruída. Neste caso, se uma partícula se move de um ponto \(A\) a um ponto \(B\), ele deve percorrer um conjunto contínuo de pontos entre esses pontos, passando por todos os pontos. Este conjunto de pontos é denominado trajetória. Por enquanto, é irrelevante a razão do movimento.Postulado 3: O movimento de uma partícula é representado por uma curva suave no espaço euclidiano tridimensional.Assim, apresentamos formalmente o conceito de movimento e seu correspondente do lado matemático do mapeamento de que tanto discutimos; a curva.

Objective: To assess whether secretory otitis media may be caused by immune imbalance of Treg/Th17 mediated by PI3K/Akt/mTOR signaling, so as to find new therapeutic target. Methods: IL-17, TGF- and IL-6, IL-10 and Th17 cytokines were detected in peripheral blood of OME patients (PC group) and healthy people (NC group) by ELISA. The expression of ROR t mRNA and Foxp3mRNA in PBMC was detected by RT-PCR. OME rat model was established and the changes of lymphocytes in middle ear mucosa and spleen and PI3K/Akt/mTOR signaling in middle ear mucosa were detected by HE staining, IHC, WB and flow cytometry. Results: The immune imbalance of Treg/Th17 in secretory otitis media (OME) was confirmed by the expression of cytokines in OME serum and analysis of ROR T and Foxp3 mRNA which was Th17 and Treg specific transcription respectively. OME rat model further confirmed that Treg/Th17 imbalance could lead to OME as demonstrated by staining of MIDDLE ear mucosa and expression of ROR T and Foxp3. PI3K, Akt, and mTOR proteins were expressed in the MIDDLE ear mucosa of OME group and CON group, respectively. Compared with CON group, the expression of P-MTOR and P-PI3K proteins in the middle ear mucosa of OME group was significantly increased. Conclusions: Treg/Th17 imbalances are found in OME patients and OME animal model and the pathogenic mechanism may be due to systemic abnormal immune response, activated PI3K/Akt/mTOR signaling, abnormal T cell differentiation, leading to middle ear mucosal hyperemia, edema and subsequent occurrence of OME.

Exercise-induced muscle damage (EIMD) causes to increased soreness, impaired function of muscles, and reductions in muscle force. Accumulating evidence suggests beneficial effects of creatine on EIMD. Nevertheless, outcomes differ substantially across various articles. The main aim of this meta analysis was to evaluate the effect of creatine on recovery following EIMD. Medline, Embase, Cochrane Library, Scopus and Google scholar were systematically searched up to July 2020. The Cochrane Collaboration tool for examining risk of bias was applied for assessing the quality of studies. Weighted mean difference (WMD), 95 percent confidence interval (CI) and random effects model, were applied for estimating the overall effect. Between studies heterogeneity was examined using the chi-squared and I2 statistic. Nine studies met the inclusion criteria. Pooled data showed that creatine significantly reduced CK concentration overall (WMD = -30.94; 95% CI: -53.19, -8.69; P = 0.006) and at three follow-up times 48, 72 and 96 hours) in comparison with placebo. In contrast, effects were not significant in LDH concentration overall (WMD = -5.99; 95% CI: -14.49, 2.50; P= 0.167), but creatine supplementation leaded to a significant reduction in LDH concentrations in trials with 48 hours measurement of LDH. The current data indicates that creatine consumption is better than rest after diverse forms of damaging and exhaustive exercise or passive recovery. The benefits relate to a decrease in muscle damage indices and Improved muscle function because of muscle power loss after exercise.

Ad oggi uno dei più rilevanti aspetti negativi di impatto ambientale è causato dagli odori di molti impianti industriali ed artigianali. Sebbene in generale non siano stati dimostrati effetti diretti sulla salute, i cattivi odori possono essere causa di indubbio e persistente fastidio per la popolazione. Questi, infatti, alterano l’equilibrio psicofisico delle persone, producendo uno stato di malessere (nausea, mal di testa, problemi respiratori) tale da condizionarne il comportamento e diventare elemento di conflitto sia nel caso di impianti esistenti, sia nella scelta del sito di localizzazione di nuovi impianti. L’odore è un fenomeno complesso da analizzare poiché la potenzialità osmogena di una miscela gassosa dipende da: aspetti soggettivi di tipo fisiologico e psicologico propri delle persone che lamentano le maleodorazioni, aspetti oggettivi propri delle sostanze che la compongono come l'idrosolubilità e la volatilità, nonché da aspetti ambientali come pressione, temperatura, umidità relativa dell’aria, velocità e direzione dei venti. E’ proprio a causa di questo complesso insieme di fattori che gli odori sono avvertiti dalle persone in modo differenziato. Nasce perciò l’esigenza di oggettivare il più possibile il problema del cattivo odore. Uno dei metodi per il monitoraggio delle emissioni odorigene delle acque reflue è quello di utilizzare IOMS (sistemi strumentali di monitoraggio degli odori) come il naso elettronico.

1. 1. Thermal imaging technology is a developing field in wildlife management. Most thermal imaging work in wildlife science has been limited to larger ungulates and surface-dwelling mammals. Little work has been undertaken on the use of thermal imagers to detect fossorial animals and/or their burrows. Survey methods such as white-light spotlighting can fail to detect the presence of burrows (and therefore the animals within), particularly in areas where vegetation obscures burrows. Thermal imagers offer opportunity to detect the radiant heat from these burrows, and therefore the presence of the animal, particularly in vegetated areas. Thermal imaging technology has become increasingly available through the provision of smaller, more cost-effective units. Their integration with drone technology provides opportunities for researchers and land managers to utilise this technology in their research/management practices. 2. We investigated the ability of both consumer (AUD$65,000) mounted on drones to detect rabbit burrows (warrens) and entrances in the landscape as compared to visual assessment. 3. Both types of imager and visual inspection detected active rabbit warrens when vegetation was scarce. The presence of vegetation was a significant factor in detecting entrances (P<0.001, α=0.05). The consumer imager did not detect as many warren entrances as either the professional imager or visual inspection (P=0.009, α=0.05). Active warren entrances obscured by vegetation could not be accurately identified on exported imagery from the consumer imager and several false-positive detections occurred when reviewing this footage. 4. We suggest that the exportable Hz rate was the key factor in image quality and subsequent false positive detections. This feature should be considered when selecting imagers. Thermal imagers are a useful additional tool to aid in identification of entrances for active warrens and professional imagers detected more warrens and entrances than either consumer imagers or visual inspection.

The structure of Apteryx’s eggshell has generated much debate over the decades because it does not fit well with most allometric predictions. Apteryx eggshells are unusually thin and have been reported to be 60% less porous than expected. It has been suggested that these adaptations are compensations for a very long incubation period. Most studies so far have been carried out in what has been reported as Apteryx australis, and using infertile eggs or eggs laid in captivity. However, A. australis once comprised all kiwi with brown plumage, now separated into three distinct species: Brown Kiwi (A.mantelli), Rowi (A.rowi), and Tokoeka (A.australis). These three species use different habitats and live at different latitudes and altitudes. In addition, captive eggs are much smaller than wild laid eggs. These confounding factors make necessary to revise the assumptions made for Apteryx in the past. In this study, we analysed the physical characteristics of the Apteryx eggshells making a comparison between the three species of brown coloured kiwi and for some of the analysis we included some specimens of Roroa (A. haastii, Great Spotted Kiwi). We found that shell characteristics are different between the different species studied. The pore area of Apteryx eggshells was higher than previously suggested, and the water vapour conductance was much closer to what is expected for an egg that size. We found several new features such as triangular mineral particles composing the cuticle, only reported for a cretaceous Theropod, and the presence of plugs and caps on the eggshell pores. We suggest that the characteristics of the eggshells of the different species relate to the mating system of each species in addition to environmental variables, particularly pluviosity. We also suggest that the erosion of the cuticle during incubation is an adaptation to a long incubation period in a burrow.

Background: Pemphigus vulgaris (PV) is a severe autoimmune skin disease. Autoantibodies in PV (PV-IgG) targeting desmoglein (DSG)1 are required for loss of desmosome adhesion and skin blistering. Objectives: The aim was to connect the single steps of a Ca2+ flux dependent pathway and show it’s importance for the pathogenesis of pemphigus vulgaris. Methods: Applied methods include immunoprecipitation, Ca2+-flux analysis with FURA2-AM, analysis of protein phosphorylation with Western-blotting, Immunofluorescence, investigation of loss of adhesion in dissociation assays and human skin ex-vivo blistering model. Results: PV-IgG but not a DSG3-specific monoclonal antibody (AK23) caused Ca2+ influx in primary human keratinocytes. Phosphatidyl inositol 4 kinase-α (PI4K) interacts with DSG1 but not DSG3. Its downstream targets, phospholipase-C-γ1 (PLC) and protein-kinase-C α, similar to p38MAPK interacted with both. PLC was activated by PV-IgG but not by AK23. PLC regulates the release of Inositol-1,4,5-trisphosphate (IP3) causing IP3-receptor (IP3R) activation and Ca2+ flux from the endoplasmic reticulum into the cytosol. This stimulates Ca2+-release-activated-channels (CRAC) causing Ca2+ influx. Inhibitors against PI4K, PLC, IP3R or CRAC effectively blocked PV-IgG-induced Ca2+ influx and ameliorated alterations of DSG1 and 3 localization, keratin filament retraction, actin disruption and loss of cell adhesion in vitro. Moreover, inhibiting PLC was protective against blister formation, redistribution of DSG1 and 3 and actin disruption in human skin ex vivo. Conclusions: These results demonstrate that Ca2+-mediated signalling is important for pemphigus pathology and dependent on the autoantibody profile, with different roles for the Dsg1 and Dsg3 complexes. PLC could be an interesting pharmaceutical target.

Rationale, aims and objectives: Cultural and linguistic diversity is a major challenge faced by speech-language pathologists (SLPs) in conducting evaluation of aphasia, especially in low-resource regions. Without proper consideration of cultural and linguistic issues when adapting English-based language tests to other languages, performance of individual with aphasia may not be valid and reliable. The present study was conducted: (a) to identify the practices of SLPs in conducting aphasia evaluation in Malaysia, which is a country consisting of multiethnic populations, and (b) to determine challenges faced by SLPs when conducting aphasia evaluation involving a diverse group of individuals. Methods: An online survey was distributed to SLPs who are practicing in Malaysia involved in the management of aphasia during the period of data collection. The questionnaire was developed to gather data on participants’ background, their practices in evaluating people with aphasia, and challenges that they face related to aphasia evaluation. Proportions were calculated for each item in the questionnaire to determine patterns related to background information, SLP practices and related challenges. Results: Malaysian SLPs were found to gather information about their patients via interviews with caregivers, medical records, and direct testing and observation. Abilities of people with aphasia that were consistently reported to be assessed frequently include auditory language comprehension, verbal expression, repetition of words and sentences, and social communication. Two major challenges identified were linguistic barrier and lack of standardized assessment tools for aphasia evaluation. Conclusions: There are some similarities in terms of SLP practices and challenges faced by the participants in comparison with other studies conducted in diverse contexts. Issues related to cultural and linguistic diversity complicates the development of appropriate resources for aphasia evaluation. Consideration of those issues in development of original and adapted evaluation tools may improve the accuracy of diagnosis, identification of severity, and planning of intervention.

ILs thermodynamic properties at variable temperature and pressure, such as density, viscosity and thermal conductivity, are necessarily basal parameters of chemical engineering process. In this paper, some norm descriptors-based QSPR models are established to predict the properties of ILs at variable temperature and pressure. The f-T-P models are developed with 9020 data points of 314 ILs for density, 7342 data points of 351 ILs for viscosity and 608 data points of 87 ILs for thermal conductivity. These models have satisfactory statistical results for the calculation of ILs properties. The validation analysis shows that these QSPR models have good stability and predictability. And the norm descriptors are universal for predicting the properties of ILs. Moreover, these QSPR models are applied to predict parameters of f-T-P models for 16329 ILs generated by combing the cations and anions in the dataset, which might be valuable and further used handily by other chemists.

This research presents a theoretical and experimental study of a solar humidification dehumidification water desalination system based on a closed-air cycle. The results show that productivity enhances with increasing air flow-rate while the gain output ratio decreases. The gain output ratio and productivity improve with raising the temperature of water. The average value of gain output ratio is 0.71, 0.74, 0.78, and 0.81, and productivity is 1.46 kg/h, 2.59 kg/h, 4.40 kg/h, and 6.99 kg/h at water temperatures of 40 °C, 50 °C, 60 °C, and 70 °C, respectively. The maximum gain output ratio of 0.86 is recorded at water to air mass flow-rate ratio of 5. Increasing the cooling water flow-rate has a positive effect on both productivity and gain output ratio. Moreover, The results indicate that the fresh water cost is 0.012 $/L. Finally, a good agreement is noted between the theoretical and experimental results.

Objective: To assess the efficacy of massage therapy on the improvement of constipation in post-stroke patients by using a meta-analysis. Methods: The randomized controlled trials on the efficacy of massage in the treatment of constipation after stroke were retrieved in PubMed, web of science, Cochrane, EBSCO, China Knowledge Resource Integrated Database (CNKI), Wan Fang Data, and Weipu Database until September 2019. These articles whose quality met the inclusion criteria will be assessed using the evaluation method which recommended by the Cochrane Collaboration. The software RevMan 5.3 provided by the Cochrane Collaboration was used. Results: A total of 15 studies with 1224 patients were included for the statistical analysis. Results showed that massage can improve the total effective rate of post-stroke constipation patients compared with conventional treatment (RR = 1.41, 95% CI = 1.22 - 1.63, P < 0.00001). Also, some secondary outcome indicators’ results were also superior to the control group, including the modified Rankin scale (SMD = -0.53, 95% CI = -1.02 - -0.04, P = 0.03), the self-rating depression scale (SMD = -1.25, 95% CI = -1.73 - -0.77, P < 0.00001) and the self-designed scales ([RR = 1.74, 95% CI = 1.26 - 2.40, P = 0.0007], [RR = 1.17, 95% CI = 0.97 - 1.42, P = 0.09], [RR = 1.92, 95% CI = 1.16 - 3.19, P = 0.01], [RR = 1.22, 95% CI = 1.09 - 1.38, P = 0.0008], [RR = 1.92, 95% CI = 1.11 - 3.30, P = 0.02]). Conclusion: Massage has certain curative effect on patients with constipation after stroke. Meta-analysis results imply that massage therapy could be a beneficial complementary treatment for a patient suffering constipation after stroke. Limited by the number and quality of the included studies, the above conclusions need to be further studied to confirm.

Ecological theory recognizes the importance of the variety of species for maintaining the functioning of ecosystems and their derived services. In this context, adaptive changes in functional traits plays a crucial role. We assert that when studying the effects of shifts in biodiversity levels using mathematical models, they must be scale--invariant, i.e., should be sensitive to the variety of species traits but not to raw species numbers. We present a testing procedure for verifying scale--invariance of eco--evolutionary network models expressed as ODEs. Furthermore, we applied our test to several influential models used for evaluating biodiversity effects on ecosystem functioning. In most of the surveyed studies the equations used failed our test. This raises doubts about the validity of previous results and calls for revisiting the theory derived from these studies. Our results foster the creation of artifact--free models, a necessary step towards building a more robust theory of ecosystem functioning.

The coarse resolution climatic data extracted from the global climate models (GCM) cannot be utilised straightaway for research works on climate change impact analysis. Thus, the downscaling technique is used to attain a higher resolution scenario from the GCM. In the current study, the Canadian Centre for Climate Modelling and Analysis (CCCma)-GCM is used to predict monthly precipitation using the statistical downscaling technique for the tropical semi-arid region of Eastern Gujarat for the period 2019-2099. Geo-potential height (h500) and mean sea level pressure (MSLP) are chosen as explanatory variables for the downscaling model. The model is developed using the principal component analysis (PCA) - multiple linear regression (MLR) combined approach. The model is applied to predict rainfall for three representative concentration pathway (RCP) scenarios, RCP2.6, RCP 4.5, and RCP 8.5. The best-suited scenario for the study area is selected using robust statistical indicators such as the Nash-Sutcliffe efficiency and the root mean square error. Several parametric and nonparametric tests are conducted to analyse rainfall trends in the Eastern Gujarat region. The outcomes showed that the precipitation scenario produced for RCP4.5 replicates the climatology of the region suitably. The trend investigation of the predicted rainfall showed that the significance of the seasonal trend is independent of the significance of monthly trends. Trend analysis of downscaled precipitation series can report multiple change points for a region. Further, the annual rainfall increases tremendously in the tropical semi-arid regions over the 21st century. This study will provide insights into sustainable water resource management and development.

Interatomic potentials laid at the heart of molecular physics. They are a bridge between the spectroscopic and structural properties of molecular systems. In this paper, a century-old review from 1920 to 2020, of functional forms used to analytically represent potential energy as a function of interatomic distance for diatomic systems is presented. With such a purpose fifty functions were selected. For all of them, motivation and the main mathematical features are discussed. Our goal is to provide a chronological pathway to the reader, even with little knowledge on the subject, to understand how to calculate each parameter that composes the interatomic potentials, as well as obtain spectroscopic constants from them. Comparative evaluation for the N2, CO, and HeH+ systems in their ground electronic states are also presented.

The geometric structures, energetic and electronic properties of global minima of the AlBen (n = 1–12) clusters have been systemically studied by using the hybrid density functional theory [B3LYP] and coupled cluster [CCSD(T)] methods. It is found that the impurity Al atom is externally bound to the host Ben framework and its maximum coordination number is six. Besides, the geometries of AlBen bear close resemblance to either local or global minimum structures of Ben+1. The AlBe3 and AlBe8 clusters exhibit high relative stability among the AlBen clusters, which is reflected by the evolutions of average atomic binding energy, dissociation energy, second difference in energy, adsorption energy of Al, and HOMO-LUMO gap with cluster size. In comparison to the pure Ben+1 clusters, AlBen exhibit larger binding energy values, whereas they are more polarizable.

Many scientists have discussed what are reasonable or appropriate ecological and epidemiological models of covid-191,2,3. Their goal lies in that their models can be used for accurately predicting covid-19 spread. Of course, the models are useful, however they should be used in practice for reducing infection risks. The airflow or ventilation control plays a key role in alleviating the infectious diseases spread4. The new research was awarded to reduce infection risks for covid-195. We should use the latest cleanroom strategy for reducing infection risks. Instead of blowing air against human indoor, sucking air against human should be used in ventilation control for disturbing virus transmission to human6. A negative pressure room will play a key role in mitigating covid-19 pandemic by controlling the airflow to avoid covid-19 viruses against human bodies6.References:Carlson, C.J., Chipperfield, J.D., Benito, B.M. et al. Don’t gamble the COVID-19 response on ecological hypotheses. Nat Ecol Evol 4, 1155 (2020). https://doi.org/10.1038/s41559-020-1279-2Carlson, C. J., Chipperfield, J. D., Benito, B. M., Telford, R. J. & O’Hara, R. B. Nat. Ecol. Evol. 4 , 770–771 (2020)Araújo, M. B., Mestre, F. & Naimi, B. Nat. Ecol. Evol .https://doi.org/10.1038/s41559-020-1246-y(2020)Morawska, L., & Cao, J. (2020). Airborne transmission of SARS-CoV-2: The world should face the reality. Environment international ,139 , 105730.https://doi.org/10.1016/j.envint.2020.105730RAPID: Smart Ventilation Control May Reduce Infection Risk for COVID-19 in Public Buildings, 2020 https://www.nsf.gov/awardsearch/showAward?AWD_ID=2029690&HistoricalAwards=false Airborne InfectiousDisease ManagementMethods for Temporary Negative Pressure Isolation prepared by Minnesota Department of Health https://www.health.state.mn.us/communities/ep/surge/infectious/airbornenegative.pdf

La presenza di antibiotici e farmaci nelle acque reflue è un problema attuale dal grande impatto ambientale, soprattutto sul comparto idrico. Infatti, determinanti quali impianti di trattamento delle acque reflue, effluenti ospedalieri ed attività civili ed industriali generano pressioni quali scarichi, applicazioni dirette di farmaci in acquacoltura, scoli di letame e liscivazioni in discarica che, se non controllate, comportano impatti sugli ecosistemi tali da non perseguire una politica di sviluppo sostenibile. Tra i farmaci presenti, quello più rilevato negli UWTP è il diclofenac (DCF). Per la sua completa rimozione bisogna utilizzare trattamenti avanzati: si ricorre all'impiego di processi ad ultrasuono (US), all’ozonizzazione (O3) e alla loro combinazione (US+O3).Gli US hanno una migliore efficienza in termini di rimozione rispetto all’O3, inoltre il processo combinato produce un degrado molto più elevato, soprattutto a basse durate, grazie allo sviluppo di radicali liberi.  

Skills in computer science can have great value in studying, doing and communicating physics. As educators, we asked ourselves how to make students aware of that, and how to offer them a new and appealing approach to physics. We also wondered how to increase students' engagement, participation and understanding, particularly when lessons are delivered online. Thus, we began a project to develop study materials for an introductory course in physics for computer science and we chose to use open source software. The materials are organized as a set of Jupyter notebooks hosted on an open GitHub repository. The notebooks deal with fundamental concepts of physics related to everyday life, offering examples of what can be done with a few lines of Python code. In the notebooks we propose activities to observe phenomena, describe problems, experiment, acquire and analyze data, and model the behavior of systems. The contents are suitable for undergraduates, high-school students, and evergreen students. We have used the materials for lectures, guided laboratory activities and presentations to freshmen and younger students, and we plan to continue with this project.

Causes of mortality from COVID-19 include respiratory failure, heart failure, and sepsis/multi-organ failure. TLR4 is an innate immune receptor on the cell surface that recognizes Pathogen Associated Molecular Patterns (PAMPs) including viral proteins and triggers the production of type I interferons and proinflammatory cytokines to combat infection. It is expressed on both immune cells and tissue-resident cells. ACE2, the reported entry receptor for SARS-CoV-2, is only present on ~1-2% of the cells in the lungs or has a low pulmonary expression, and recently the spike protein has been proposed to have the strongest protein-protein interaction with TLR4. Here we review and connect evidence for SARS-CoV-1 and SARS-CoV2 having direct and indirect binding to TLR4, together with other viral precedents, which when combined shed light on the COVID-19 pathophysiological puzzle. We propose a model in which the SARS-CoV-2 spike glycoprotein binds TLR4 and activates TLR4 signalling to increase cell surface expression of ACE2 (since it is a human interferon-stimulated gene, expressed downstream) in order to enter the cells. This would allow SARS-CoV-2 to infect more cells whether in the lungs or heart. SARS-CoV-2 also destroys the type II alveolar cells that secrete pulmonary surfactants, which normally decrease the air/tissue surface tension and block TLR4 in the lungs. This not only leads to a sharp reduction in pulmonary surfactants, breathing difficulties and ARDS, thereby explaining the symptoms, but also exposure of TLR4 on the lung cells allowing more viral infection and inflammation. Furthermore, SARS-CoV-2 is likely causing myocarditis and multiple-organ injury by triggering excessive TLR4 activation and aberrant TLR4 signalling; favouring the canonical MyD88- dependent pro-inflammatory pathway, over the alternative TRIF/TRAM-dependent anti-inflammatory and interferon pathway. This may also explain in part, the severe hyperinflammation or “cytokine storm” that occurs in COVID-19 patients. The TLR4 pathway triggered may depend on the cell type and stage of infection. Moreover, Damage Associated Molecular Patterns (DAMPs) released from necrotic cells further activate TLR4 to cause inflammation, and possibly fibrosis. There are also possibilities that SARS-CoV-2 may use TLR4 to enter the cells via internalisation into endosomes in the alternative pathway or activate TLR4 on platelets to cause pro-thrombotic events. A number of clinical trials have been initiated testing the use of pulmonary surfactants in COVID-19 patients, similar to treating Neonatal Respiratory Distress Syndrome. Pulmonary surfactants would prevent alveolar collapse, prevent infection of naïve cells and block TLR4 from the virus and/or DAMPs. TLR4 antagonists have also been trialled in sepsis or in an antiviral context and may be useful in the treatment of COVID-19. As such, we believe that TLR4 contributes significantly to the pathogenesis of SARS-CoV-2 and its over-activation causes a prolonged or excessive innate immune response.

Science is not just about knowing but also about experiencing. Today with the boon of technological advancement we have easy access to information and knowledge which is merely a click away with the advent of technological transformation. Science is largely about learning and it majorly comes through the experience. So, it's more important how you can make the experience of science more accessible to a lot of people around the world. The actual experience of science is utilizing scientific tools to make your own discoveries. Prof. Manu Prakash at Stanford University \cite{lab} is in a quest of how can we make scientific tools that are so affordable, which are like buying a pencil from a shop, So what it would mean if a scientific tool is as accessible as pencil? What you would actually do, would you sketch with it or would you write a poetry with it, what exactly is the end of that for science? This really can be done across different fields by making scientific devices and tools for all. So how do you make the microscopic world easily visible, it's just around you but most people haven't actually seen it.  What a feeling of wonder it would be for all the people to zoom into that invisible world which we are part of. Frugal Science which came out as a philosophy is now an innovative research field. Frugal Science is a type of research focusing on the development of scientific tools that are far cheaper and more accessible to the average person \cite{wikipedia}. Accessibility is a big challenge that science is facing. facing. The day is not far when we can have devices for point of care applications in our pocket, the devices which are versatile and robust. We can have diagnostics of deadly infectious diseases in the field with simple and easy devices without the sophisticated instruments and expertise. Improve the quality of treatment and also decrease the cost so that broad community of people can benefit. \cite{sciencea}Science doesn't always have to be costly. This way people can experience the science and can make them more curious, have them discover this new world and interpret it in their own way. With frugal science we can have designers and inventors at every home, you just need nourish your curiosity as we know, "Curiosity is the mother of inventions". With accessibility to frugal tools people can unleash and discover the world and experience the science for themselves. Also, this can lead to transformation in global health solutions and making healthcare accessible to the most remote parts of the world and making it more affordable. There are plenty of problems around us which are in urgent need to be addressed but with simple solutions. We need many frugal scientist for together making this world a better place to live. Be Crazy Be Curious!!

A document by Chiman Kumari. Click on the document to view its contents.

Corporate Information Models(CIM) are Online Analytical Processing (OLAP) Cubes – a data structure that enables simple and rapid analysis of data by the multiple dimensions that define a business challenge. A multidimensional cube for reporting composed of multiple Dimension e.g. Customers, Product Lines, business units and Date. By storing data using OLAP cubes, data is pre-calculated and ready-to-use, eliminating long-running data queries and enabling self-service business intelligence. A portal has been developed to provide and display the CIM detail. The CIM catalog links to over 60 CIMs categorized by the seven main categories called Value streams.

A física fundamentalSe o objetivo da física é explicar a natureza da matéria em nível fundamental (este não é o único objetivo, mas certamente um de grande motivação), o nível mais profundo de compreensão que temos hoje é o Modelo Padrão das partículas elementares. A Fig. \ref{826089}  classifica as partículas elementares  de acordo com a massa, carga elétrica e spin. No modelo padrão, a matéria é constituída por férmions e bósons. No geral, os férmions são os blocos construtores da matéria, enquanto os bósons participam do processo de interação. Férmions são separados em quarks, partículas massivas com carga elétrica e carga de cor, o que os torna sucetíveis à força nuclear forte, e léptons, como o elétron, que são massivos e podem possuir cargas elétricas definidas. As partículas de interação são denominados Bósons de Gauge e são os portadores das três forças fundamentais constituintes do modelo (a gravitação não está incluída). O Bóson de Higgs, recém descoberto mas previsto pela Teoria Quântica de Campos desde a década de 1960, figura como a única partícula elementar conhecida de spin zero.