Uncontrolled Development Research Articles

Conservation of Ecological Sensitive Regions with the insights of forest dynamics at disaggregated levels

Ecological sensitivity or fragility refers to permanent and irreparable loss of extant life forms or significant damage to the natural processes of evolution and speciation with the alterations in the ecological integrity of a region. The comprehensive knowledge of the ecological fragility of a region is quintessential for evolving strategies of conservation. This entails understanding factors responsible for ecological sensitiveness, including landscape dynamics, to visualize future transitions to mitigate the problems of haphazard and uncontrolled development approaches. The assessment of forest dynamics for Dakshina Kannada district was carried out using temporal remote sensing data and the field data and predicted future scenarios of transformation, which helps develop appropriate management strategies. Ecological sensitive regions at decentralized levels (grids of 5’ x 5’ or 9 km x 9 km) have been identified in Dakshina Kannada district, Karnataka State, India, through a composite metric based on bio, geo, hydro, climatic, and ecological factors with the social aspects. This information was compiled through natural environment survey at representative grids and the extensive literature review for the information at the district level. The 33% (24 grids) of the area corresponds to 54 villages represents ESR 1, 20% (15 grids) of the area demarcated as ESR 2 covering 81 villages, 28% (20 grids) of the area covering 145 villages shows ESR 3, and 19 % area (14 grids) covering 100 villages as ESR 4. ESR 1 & ESR 2 indicates the high ecological sensitiveness, need to be protected, and suggested stringent conservation measures. ESR 3 represents a moderate conservation region, and only regulated development is allowed. ESR 4 represents the least diverse areas, and the developments are permitted as per the requirement of local people through strict vigilance of regulatory authorities. The region-specific (cluster approaches in the development path to enhance job opportunities and optimization of local resources use) sustainable developments can be taken up at each panchayat level, with the most negligible effects on the ecosystem.

A Place-based Approach to Assess the Vulnerability of Communities to Urban Floods: Case of Nagpur, India

Amongst all disasters, flood is the most incessant disaster influencing a noteworthy number of individuals all around the world. The developing countries have been profoundly affected by the calamities, due to excessive loss of lives and assets. The city of Nagpur in Maharashtra, India, is prone to water related disasters. In addition, the uncontrolled development has worsened the floods events. The existing physical infrastructure and social attributes have made the population vulnerable to urban floods. The study focuses on conducting a micro-scale i.e., community vulnerability assessment by identifying the drivers of vulnerability. A questionnaire based on the socio-economic and infrastructure characteristics was formulated and a primary survey was conducted. The study involved application of principal component analysis by means of python programming to develop socio-economic and physical infrastructure indices. The analysis enabled component wise and index wise visualization of low vulnerable to high vulnerable zones in Nagpur using Geographic Information System (GIS). The goodness-of-fit for socio-economic and physical infrastructure vulnerability index show R2 value as 0.7219 and 0.7058 respectively, suggesting the models to be substantial. This robust vulnerability framework can gauge the real conditions of the population thereby assist in developing policies and strategies to reduce the impact of urban floods.

Head and Neck Cancer Susceptibility and Metabolism in Fanconi Anemia.

Simple SummaryGermline loss-of-function mutations in any of over 20 known Fanconi anemia (FA) genes cause the disorder FA. The FA pathway plays a key role in the repair of DNA interstrand crosslinks (ICLs) and stabilization of stalled replication fork. Epidemiological studies have shown that persons with FA have a uniquely increased susceptibility to squamous cell carcinomas (SCCs) and increased human papilloma virus (HPV) prevalence. Genomic and transcriptomic studies are informative, but there is a paucity of data regarding metabolic deregulation in FA deficient systems. Metabolism is an essential component of cancer development and has significant impact on therapeutic outcomes. Therefore, a deeper understanding of the metabolic architecture of FA may aid in our understanding of SCC development, and allow for the discovery of metabolism-based diagnostic biomarkers and new therapeutic targets. In this review, we discuss known metabolic consequences of FA pathway loss on cancer pathogenesis, and in particular in normal and transformed keratinocytes—the cells of origin for SCC.Fanconi anemia (FA) is a rare inherited, generally autosomal recessive syndrome, but it displays X-linked or dominant negative inheritance for certain genes. FA is characterized by a deficiency in DNA damage repair that results in bone marrow failure, and in an increased risk for various epithelial tumors, most commonly squamous cell carcinomas of the head and neck (HNSCC) and of the esophagus, anogenital tract and skin. Individuals with FA exhibit increased human papilloma virus (HPV) prevalence. Furthermore, a subset of anogenital squamous cell carcinomas (SCCs) in FA harbor HPV sequences and FA-deficient laboratory models reveal molecular crosstalk between HPV and FA proteins. However, a definitive role for HPV in HNSCC development in the FA patient population is unproven. Cellular metabolism plays an integral role in tissue homeostasis, and metabolic deregulation is a known hallmark of cancer progression that supports uncontrolled proliferation, tumor development and metastatic dissemination. The metabolic consequences of FA deficiency in keratinocytes and associated impact on the development of SCC in the FA population is poorly understood. Herein, we review the current literature on the metabolic consequences of FA deficiency and potential effects of resulting metabolic reprogramming on FA cancer phenotypes.

SPATIAL MODEL OF WETLAND USE CHANGE AND FLOOD OCCURRENCE IN RESIDENTIAL AREAS

This paper discusses the relationship between wetland use change and the occurrences of ftoods in residential areas of Palembang City. Palembang, well known as a wetland city in early 1919, has significantly converted its wetland up to 55% in 2010. The trend of flooding in the city has increased from 18 events in 2007 to 46 events in 2012. Uncontrolled urban development is assumed as the major drivers of the wetland conversion. The aim of this study is to estimate the relationship between land use change and the occorrence of flood happened in Palembang. In this paper, approximately 626 households from 4 residential areas were observed and 26 respondents were interviewed in March 2014 to gain information about the environment before, during and after the flooding and their relation to the wetland conversion. Literature review was also conducted in order to gain more insights about the phenomenon. By harnessing spatial correlation analysis, this study presents the relation between wetland conversion trend and flood occurrence in Palembang, which could be used to develop the appropriate policy to reduce the risks coming from flooding as well as preserving the urban environment in Palembang.

Qualitative and Quantitative Characterization of Municipal Waste in Uncontrolled Dumpsites and Landfills Using Integrated Remote Sensing, Geological and Geophysical Data: A Case Study

The conducted research offers an environmental assessment of municipal waste (MW) using remote sensing (RS), geological, and geophysical datasets. As a test site, the present study aims to characterize one of the largest uncontrolled dumpsites in Egypt. RS data analysis indicates that high temperature values are concentrated at the MW and landfill site allocations as a result of the decomposition process, leading to fire risks. Moreover, the geological and structural data draw attention to the structural-controlled old topography role on MW distributions. Consequently, the dumpsite MW has larger surface quantities near the downthrows of the mapped faults. For MW characterization, geophysical data are acquired to produce2D/3D resistivity models. Because MW has the ability to become soft clay, the municipal organic waste and landfill leachate resistivities are lower than that of municipal solid waste and sandy soils. The geophysical inversion results indicate that the maximum thickness of MW calibrating with the drilled borehole data is 60 m. Furthermore, the estimated MW dumpsite volume is about 42.32 MCM. Accordingly, the MW can be characterized in an accurate qualitative and quantitative manner. Our findings, therefore, help the efforts of uncontrolled dumpsite development and thus contribute to sustainability plans.

Disaster risk management: Focused to flood hazard and its impact in Pakistan

<p>Recently, weather and climate related extreme occasions circumstances such as droughts, heat waves, bush fires and floods are increasing around the world. South Asian countries, that have the highest annual average number of people physically affected by natural hazards mostly by floods. Most popular flood risk areas are urban areas because there is rapid urbanization infrastructure and uncontrolled development. These are the most common factors that It results in more people being vulnerable to natural hazards floods than ever before. Pakistan is positioned within a hazard-prone region and is exposed to several kinds of natural disasters such as earthquakes, cyclones, landslides, droughts and floods but still it lacks proper disaster management policies. Floods in Pakistan bring a great destruction both in urban and rural areas. This paper focuses on some of the key benefits that may be achieved in presence of a proper disaster management framework or policies and also it proposes latest technologies to deal with hazards. This paper also demonstrates a simple concept that may be adopted and implemented immediately, that may help to minimize the impact economically, socially and environmentally.</p>

NFV-Based Scheme for Effective Protection against Bot Attacks in AI-Enabled IoT

The Internet of Things (IoT) is the upcoming network that aspires to interconnect “things” to each other and to the Internet. Many such “things” like smart devices and wireless sensors are already connected to the Internet, improving human life worldwide. These things can also have artificial intelligence, providing many capabilities to their users. However, such IoT-based devices hide risks since they are usually small devices with constrained resources, and hence do not have sufficient built-in security mechanisms. In addition, the increase of such devices with geometric regression worries network administrators who must take countermeasures to restrict and eliminate attackers who aim to turn the IoT into a Botnet of Things network, using compromised devices as bots to unleash distributed-denial-of-service and man-in-the-middle attacks, or/and spread various types of malware. Thus, they can have unauthorized access and steal very sensitive data from users for malicious purposes. In this article, we highlight the problem caused by the uncontrolled development of insecure IoT-based devices and describe an effective network functions virtualization infrastructure in combination with emerging technologies that could provide smart management and enhanced protection against botnet attacks.

Systematic identification of genes encoding cell surface and secreted proteins that are essential for in vitro growth and infection in Leishmania donovani.

Leishmaniasis is an infectious disease caused by protozoan parasites belonging to the genus Leishmania for which there are no approved human vaccines. Infections localise to different tissues in a species-specific manner with the visceral form of the disease caused by Leishmania donovani and L. infantum being the most deadly in humans. Although Leishmania spp. parasites are predominantly intracellular, the visceral disease can be prevented in dogs by vaccinating with a complex mixture of secreted products from cultures of L. infantum promastigotes. With the logic that extracellular parasite proteins make good subunit vaccine candidates because they are directly accessible to vaccine-elicited host antibodies, here we attempt to discover proteins that are essential for in vitro growth and host infection with the goal of identifying subunit vaccine candidates. Using an in silico analysis of the Leishmania donovani genome, we identified 92 genes encoding proteins that are predicted to be secreted or externally anchored to the parasite membrane by a single transmembrane region or a GPI anchor. By selecting a transgenic L. donovani parasite that expresses both luciferase and the Cas9 nuclease, we systematically attempted to target all 92 genes by CRISPR genome editing and identified four that were required for in vitro growth. For fifty-five genes, we infected cohorts of mice with each mutant parasite and by longitudinally quantifying parasitaemia with bioluminescent imaging, showed that nine genes had evidence of an attenuated infection although all ultimately established an infection. Finally, we expressed two genes as full-length soluble recombinant proteins and tested them as subunit vaccine candidates in a murine preclinical infection model. Both proteins elicited significant levels of protection against the uncontrolled development of a splenic infection warranting further investigation as subunit vaccine candidates against this deadly infectious tropical disease.

Practice and Politics of Land Use for Urban Climate Mitigation and Adaptation in Blantyre and Lilongwe Cities, Malawi

Malawi’s population is fast growing, with a good share of urban residents being susceptible to environmental risks and disasters. This risk is aggravated by climate change. Blantyre and Lilongwe cities are not spared by this scenario. The study used household survey, key informant interviews, observation, and experience to gather primary data, and desk study to solicit secondary data. Random and purposive sampling was employed to identify survey respondents and informants, respectively. Content analysis was used to establish themes and relationships. A good number of regulatory frameworks (policies) and programmes for abating urban climate change mitigation and adaptation have been in place, but implementation is a challenge. Political interference tends to shift priorities on policies to be implemented at one particular point in time of a political regime, and this has culminated into a sour relationship between politics and land use planning, with the former jeopardizing the practice by the latter. Funding insufficiency, uncontrolled development, political interference, corruption and lack of transparency, insufficient stakeholder engagement, and poor planning contribute to poor and insufficient disaster risk management, and to increased disaster risks in Blantyre and Lilongwe cities. Citizen involvement in appropriate and effective land use planning process, regular communication on the availability of safety information, and robust emergency notification system can make communities in Lilongwe and Blantyre cities resilient from climate-related risks. The urban governance system has to be strengthened. There is need for adequate political will for mobilization of urban climate governance efforts.

"A Review of Cancer Stem Cells in Solid Tumors "

Cancer is defined by the uncontrolled development of aberrant cells that may infiltrate and destroy surrounding tissues. This description suggests that all cancer cells inside a tumour are aberrant in the same way, and therefore have the same ability to start and maintain the tumour. It has long been recognized that the individual cells that make up a tumour may have considerable functional and morphologic heterogeneity. A growing body of data suggests that many solid tumour are structured in a hierarchical fashion, with the small fraction of cancer stems cells as well as tumors initiating cell driving tumour development. These cell are the only ones capable of starting and driving tumour development, although making up a tiny proportion of the total tumour population. CSCs may be resistant to chemotherapy as well as radiation treatment, according to new research, which has sparked a lot of discussion and curiosity about their potential therapeutic use.

Immunosenescence, Inflammaging, and Frailty: Role of Myeloid Cells in Age-Related Diseases.

The immune system is the central regulator of tissue homeostasis, ensuring tissue regeneration and protection against both pathogens and the neoformation of cancer cells. Its proper functioning requires homeostatic properties, which are maintained by an adequate balance of myeloid and lymphoid responses. Aging progressively undermines this ability and compromises the correct activation of immune responses, as well as the resolution of the inflammatory response. A subclinical syndrome of “homeostatic frailty” appears as a distinctive trait of the elderly, which predisposes to immune debilitation and chronic low-grade inflammation (inflammaging), causing the uncontrolled development of chronic and degenerative diseases. The innate immune compartment, in particular, undergoes to a sequela of age-dependent functional alterations, encompassing steps of myeloid progenitor differentiation and altered responses to endogenous and exogenous threats. Here, we will review the age-dependent evolution of myeloid populations, as well as their impact on frailty and diseases of the elderly.

Recent developments in the synthesis and anti-cancer activity of acridine and xanthine-based molecules

Abstract Cancer is the uncontrolled growth and development of abnormal cells which is a major cause of death in both advanced and emerging countries. Although currently chemotherapy is most broadly used among an extensive range of anti-cancer therapies, it includes many demerits, such as highly toxic, side-effects, expensive and partial lack of targeting specificity. So the design and synthesis of new molecules that perform specifically on target proteins in tumor cells is a focus of contemporary research. So many researchers aim for new drugs that will be more efficient, more selective, and less toxic. Because of the interesting structures and significant biological profile, naturally occurring acridines and xanthines as well as their analogues have attracted considerable interest in researchers and technologists. Natural and synthetic acridine derivatives form a significant category of heterocycles having nitrogen that is of considerable interest for organic chemists and biological communities due to their attractive anti-cancer activity. Another important class of therapeutic agents with diverse biological properties including cytotoxic effects is xanthine derivatives which are collectively called xanthines (a group of alkaloids). Among many significant molecules based on the structure of the purine, there is a group of natural xanthines, involving theobromine, caffeine, and theophylline and analogues of xanthine display anti-cancer activity. Hence the present chapter wishes to concentrate the attention on the synthesis and anti-cancer activity of acridine and xanthine-based compounds brilliantly.

Disonanca kao koncept očuvanja graditeljskog nasleđa - studija slučaja Beogradskog sajmišta

Belgrade Fairground, built in the 1930s, was the first urban complex designed according to modern principles and the first physical structure built in Belgrade on the left bank of the Sava. During its existence, the complex has undergone radical changes - from a fairground, through a concentration camp during World War II, an art colony in the post-war period, to its current state as a marginalized urban segment inhabited by the homeless, with uncontrolled commercial development . These transformations over time have resulted in the creation of numerous layers of identity, which, from a contemporary point of view, the space itself should testify to. The paper examines the transformations that have taken place in the space, and refers to the mutually opposed events that to some extent have hindered the recovery and development of the former Belgrade Fairground. The paper, in the form of a case study, analyzes the space by exploring the application of dissonance in preserving and revitalizing the architectural heritage, since the concept of dissonance is important for articulating opposing meanings and emphasizing the plurality of values. In order to shed light upon all the characteristic phases of the complex's existence, its morphological transformations and then its functional transformations were analyzed, followed by a presentation of how its social relationship with the Belgrade Fairground has been transformed. Accordingly, the ultimate goal was to find a way to manifest the diversity of the fairground's value and its re-perception as belonging to the urban space.

ПРОГРЕСУЮЧИЙ ЛЕГЕНЕВИЙ ФІБРОЗ У СВІТЛІ ПОЛОЖЕНЬ КЛІНІЧНОЇ НАСТАНОВИ ATS/ERS/JRS/ALAT 2022 РОКУ

Idiopathic pulmonary fibrosis – is a specific form of chronic, progressive, fibrosing interstitial pneumonia of unknown cause, which occurs primarily in 50 years and older patients, limited to the lungs, and is associated with the histopathologic and/or radiologic pattern of usual interstitial pneumonia (UIP). In 2000 American thoracic society (ATS) and European respiratory society (ERS) published the first international; statement on diagnosis and treatment of IPF American Thoracic Society, European Respiratory Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. In 2011 there was published a new statement on diagnosis and treatment of IPF, approved by Japan respiratory society (JTS) and Latin American thoracis society (ALTS) – An Official ATS/ERS/JRS/AL : Idiopathic Pulmonary Fibrosis: Evidence-based Guidelines for Diagnosis and Management. In 2015 section “Treatment” and in 2018 section “Diagnosis” were revised. It is known that in part of patients with such interstitial lung diseases (ILD) as idiopathic interstitial pneumonia, systemic sclerosis, pneumoconiosis, chronic hypersensitivity pneumonitis, sarcoidosis the disease may acquire a progressive uncontrolled development with the combination of symptoms called progressive pulmonary fibrosis (PPF). At the same time the results of successful use of antifibrotic therapy have been published recently (SENSCIS, INBUILD studies). All this provided the rationale for extended indications for use of antifibrotic therapy to cover other ILDs with the features of PPF. In this connection, ATS, ERS, JRS and ALAT experts published in May 2022 An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults, in which along with the partial changes regarding the principles of diagnosis and treatment of IPF, the definition, diagnosis criteria and management of PPF due to other fibrosing ILDs were presented. The article presents the major statements of new guideline regarding the terminology, diagnosis and treatment of PPF. Key words: progressive pulmonary fibrosis, definition, diagnosis criteria, treatment.

Metaverses for Нuman or Human for Metaverses

The article researches the grounds on which the leading technology companies seek to transform the mankind’ way of life of and the nature of the "human", using the idea of "metaverses" as a promising project for the development of the Internet. The authors compare this idea with the concept of the "Panopticon" and, as a result of the analysis, draw attention to the opportunities and the threats that metauniverses pose for humanity in the conditions of uncontrolled development of technologies. The authors come to the conclusion that for successful development it is necessary to form and disseminate a new socio-humanitarian rationality, which will allow to ensure control over the activities of technology companies.

Mechanical and Thermal Properties of Biodegradable Composites Based on graft copolymer LLDPE-g-MA/Gelatin

The uncontrolled development of morphology at the stage of formation of biodegradable compositions based on synthetic and natural polymers limits the possibility of achieving satisfactory physical and mechanical and operational characteristics. In the present work, to achieve finely dispersed mixture morphology, an approach was proposed for reactive mixing of functionalized polyethylene with gelatin to form a linear low density polyethylene-grafted-maleic anhydride and gelatin (LLDPE-g-MA/GEL) graft copolymer. Using the selective extraction of the mixture components, we determined amount of graft copolymer LLDPE-g-MA/GEL, free gelatin, mechanical and thermal properties, as well as biodegradability data. It was found that as the amount of maleic groups in the polyethylene macromolecule increased, the amount of graft copolymer increased, and an increase in the content of gelatin in the blend led to a noticeable increase in the elastic modulus, tensile strength, and a decrease in elongation at break. Due to the degradation of gelatin, the thermal stability of the composite (initial temperature) decreased with increasing gelatin content. The maximum rate of destruction of the graft copolymer in the temperature range of 400–500 ºC increased markedly with an increase in the content of gelatin. It was found that the rate of biodegradability would increase with an increase in the content of gelatin in the blend; the maximum level of degradation was observed during the first 10 days and was more than 50 %. It was found that the maximum degree of grafting LLDPE-g-MA and gelatin to each other depended on the amount of maleic anhydride in the graft copolymer. The maximum degree of grafting was ob-served to be higher with increasing amount of maleic anhydride in the composites.

ОСНОВНЫЕ ПРОБЛЕМЫ ВОДОХОЗЯЙСТВЕННОЙ ОТРАСЛИ ДАГЕСТАНА

The article shows the most significant problems of functioning and development of the water economy of the Republic of Dagestan. The results of a comprehensive analysis of the state of the waters of the Caspian Sea are presented, which shows that the main pollutants here are coastal cities and other settlements with their sewage and other wastes of human activity. It is noted that most of the sewage water is now discharged into the sea directly, without passing through sewage treatment plants. The extremely unfavorable ecological situation in the coastal part of the sea serves as a serious deterrent to the development of the tourist and resort economy in the region under consideration. The authors argue that without progressive changes in the work of the port economy of the capital of Dagestan and its other coastal cities, success in the construction of seaside resorts in the Caspian Sea is unlikely. The article reflects the ecological state of Dagestan reservoirs and watercourses. It is argued about the need to return the Terek River to its natural delta, in particular, it involves the restoration of its estuarine reservoirs. Special emphasis is placed on the task of stopping uncontrolled development and recreational use of mountain reservoirs – the main sources of drinking water in Dagestan. The medical and hygienic condition of water supply sources, in particular, the level of contamination of groundwater used for drinking purposes, are discussed. The issues of water supply and sanitation (non-centralized, centralized, departmental and communal) are considered in detail. It is pointed out that urban and district centralized water supply systems do not meet sanitary and hygienic standards and almost all cities of the republic are experiencing an extreme shortage of treatment facilities. The course of implementation of a number of federal programs to improve the water supply systems of the population of the republic is described.

Hyperspectral Image Analysis of Colon Tissue and Deep Learning for Characterization of Health care.

Colon cancer is a disease characterized by the unusual and uncontrolled development of cells that are found in the large intestine. If the tumour extends to the lower part of the colon (rectum), the cancer may be colorectal. Medical imaging is the denomination of methods used to create visual representations of the human body for clinical analysis, such as diagnosing, monitoring, and treating medical conditions. In this research, a computational proposal is presented to aid the diagnosis of colon cancer, which consists of using hyperspectral images obtained from slides with biopsy samples of colon tissue in paraffin, characterizing pixels so that, afterwards, imaging techniques can be applied. Using computer graphics augmenting conventional histological deep learning architecture, it can classify pixels in hyperspectral images as cancerous, inflammatory, or healthy. It is possible to find connections between histochemical characteristics and the absorbance of tissue under various conditions using infrared photons at various frequencies in hyperspectral imaging (HSI). Deep learning techniques were used to construct and implement a predictor to detect anomalies, as well as to develop a computer interface to assist pathologists in the diagnosis of colon cancer. An infrared absorbance spectrum of each of the pixels used in the developed classifier resulted in an accuracy level of 94% for these three classes.

Panchayati Raj and Environmental Protection A Study

Environmental imbalance is not only a threat to humans, nature and animals, but also to the human and social environment. In the beginning, human and ecological interactions were balanced, such as population growth, indiscriminate deforestation, hunting of forest animals, development of technical knowledge and excessive exploitation of natural resources have led to environmental problems. Politicians and scholars who consider development as an essential condition of freedom, equality and democracy have forgotten that uncontrolled development leads us to disaster. There is a need to make Panchayat Raj institutions stronger and more democratic to make development proper and co-ordinating. Due to the problem of environmental crisis being worldwide, it is not only the responsibility of the state, government or panchayats, but every citizen has to change his lifestyle, conscious and aware and according to environmental protection. Keeping all these points in mind, a study of the role of Panchayat Raj Institutions in environmental protection has been done in this article.

Общественные изменения при цифровизации экономики

Social changes in the digitalization of the economy have a pronounced relevance. The economy is becoming digital and this acceleration is spurred by the pandemic. Social changes during the digitalization of the economy have a positive direction, which is due to various reasons. Innovation and startups play a special role, driving the digital economy. The digital economy is an example of environmental friendliness, optimality, rationality, saving intellectual, physical, labor and natural resources. At the same time, the digital economy also carries enormous risks, which include hacking, cybercrimes, cyber fraud and the uncontrolled development of artificial intelligence technologies. Lack of national and international control over the development and use of these technologies can endanger the existence of humanity.