| 1. |
- Agrawal, Mukta, et al.
(författare)
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Recent advancements in liposomes targeting strategies to cross blood-brain barrier (BBB) for the treatment of Alzheimer's disease
- 2017
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 260, s. 61-77
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Forskningsöversikt (refereegranskat)abstract
- In this modern era, with the help of various advanced technologies, medical science has overcome most of the health-related issues successfully. Though, some diseases still remain unresolved due to various physiological barriers. One such condition is Alzheimer; a neurodegenerative disorder characterized by progressive memory impairment, behavioral abnormalities, mood swing and disturbed routine activities of the person suffering from. It is well known to all that the brain is entirely covered by a protective layer commonly known as blood brain barrier (BBB) which is responsible to maintain the homeostasis of brain by restricting the entry of toxic substances, drug molecules, various proteins and peptides, small hydrophilic molecules, large lipophilic substances and so many other peripheral components to protect the brain from any harmful stimuli. This functionally essential structure creates a major hurdle for delivery of any drug into the brain. Still, there are some provisions on BBB which facilitate the entry of useful substances in the brain via specific mechanisms like passive diffusion, receptor-mediated transcytosis, carrier-mediated transcytosis etc. Another important factor for drug transport is the selection of a suitable drug delivery systems like, liposome, which is a novel drug carrier system offering a potential approach to resolving this problem. Its unique phospholipid bilayer structure (similar to physiological membrane) had made it more compatible with the lipoidal layer of BBB and helps the drug to enter the brain. The present review work focused on various surface modifications with functional ligand (like lactoferrin, transferrin etc.) and carrier molecules (such as glutathione, glucose etc.) on the liposomal structure to enhance its brain targeting ability towards the successful treatment of Alzheimer disease.
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| 2. |
- Allinne, Jeanne, et al.
(författare)
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IL-33 blockade affects mediators of persistence and exacerbation in a model of chronic airway inflammation
- 2019
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749. ; 144:6, s. 1624-1637
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Tidskriftsartikel (refereegranskat)abstract
- Background: Severe inflammatory airway diseases are associated with inflammation that does not resolve, leading to structural changes and an overall environment primed for exacerbations. Objective: We sought to identify and inhibit pathways that perpetuate this heightened inflammatory state because this could lead to therapies that allow for a more quiescent lung that is less predisposed to symptoms and exacerbations. Methods: Using prolonged exposure to house dust mite in mice, we developed a mouse model of persistent and exacerbating airway disease characterized by a mixed inflammatory phenotype. Results: We show that lung IL-33 drives inflammation and remodeling beyond the type 2 response classically associated with IL-33 signaling. IL-33 blockade with an IL-33 neutralizing antibody normalized established inflammation and improved remodeling of both the lung epithelium and lung parenchyma. Specifically, IL-33 blockade normalized persisting and exacerbating inflammatory end points, including eosinophilic, neutrophilic, and ST2+CD4+ T-cell infiltration. Importantly, we identified a key role for IL-33 in driving lung remodeling because anti–IL-33 also re-established the presence of ciliated cells over mucus-producing cells and decreased myofibroblast numbers, even in the context of continuous allergen exposure, resulting in improved lung function. Conclusion: Overall, this study shows that increased IL-33 levels drive a self-perpetuating amplification loop that maintains the lung in a state of lasting inflammation and remodeled tissue primed for exacerbations. Thus IL-33 blockade might ameliorate symptoms and prevent exacerbations by quelling persistent inflammation and airway remodeling.
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| 3. |
- Dixit, Sudhir, et al.
(författare)
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Connecting the Unconnected
- 2022
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Ingår i: 2022 IEEE FUTURE NETWORKS WORLD FORUM, FNWF. - : IEEE. - 9781665462501
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Konferensbidrag (refereegranskat)abstract
- Connecting the Unconnected or under-connected (CTU) is the holy grail of transforming the lives of over 3 billion people around the globe with wireless Internet who are yet to experience its value in multiple ways. If this could be accomplished, its impact on the society would be enormous. This white paper from the IEEE Future Networks CTU Working Group endeavors to highlight the need to consider the CTU requirements in 5G and B5G networks in the standardization process, in the development of the use cases, and affordable solutions. In its Vision 2030 SDG (Sustainability Development Goals) the United Nations has proclaimed access to Internet as basic human right and has said that these goals cannot be achieved without affordable access to Internet by everyone on this planet. While there are numerous projects and initiatives ongoing around the world, these are fragmented and lack the critical mass and coordination to be able to impact the future standards, product development, and cost of deployment otherwise achievable by volume. Although difficult to pin down, to define a threshold for basic connectivity for all is important. But it would need to be flexible to adapt to changing times. It is the goal of the CTU group to create an open platform where the experts can bring their ideas, solutions, and potentially collaborate to create large global projects and influence the network service providers, manufacturers and their governments. This white paper defines the CTU working group's charter, scope, and provides a brief overview of the relevant stakeholders and linkages between them. Then the paper goes into the current status of the CTU landscape and where we want to reach to accomplish the vision of connecting everybody, especially those living in rural and remote areas. We present the various standards and industry fora and how they are interlinked. While technologies are available today, they need to be customized and optimized at the systems level to bring down the cost of the network in order to be affordable. In addition, the content needs to be relevant and in local languages to be useful, not to mention the need to offer innovative human computer interaction (HCI) solutions (that are not text based) so that people who are not literate or are digitally disadvantaged can easily use the devices and consume services. Another important area is that of flexible spectrum allocation regime at the lower range of the spectrum to increase reach and coverage. Use of renewable energy sources will enable deployment in remote areas where there is lack of power grid, or it is intermittent. Thus, this white paper identifies a number of technology gaps to be filled in by 5G and B5G networks, such that access is affordable and content and services are actually consumed by the targeted set of users. Technology aside, the need to develop innovative business models is a must to be commercially sustainable in the long-term. A number of such models, especially designed for the rural population, are proposed, such as Village Level Entrepreneur (VLE) Freemium (Free + Premium), revenue sharing among the chain of service providers, subsidized billing by USOF (Universal Service Obligation Funds). Finally, the white paper presents a 10-year roadmap starting from the current state to 3 years, 5 years and 10 years.
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| 4. |
- Kinyoki, DK, et al.
(författare)
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Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017
- 2020
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Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 26:5, s. 750-759
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Tidskriftsartikel (refereegranskat)abstract
- A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic.
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| 5. |
- Mitra, Siddharth, et al.
(författare)
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Characterizing Web-based Video Sharing Workloads
- 2009
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Ingår i: Proc. International World Wide Web Conference (WWW ’09), Madrid, Spain, April 2009. - 9781605584874 ; , s. 1191-1192
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Konferensbidrag (refereegranskat)
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| 6. |
- Mitra, Siddharth, et al.
(författare)
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Characterizing Web-Based Video Sharing Workloads
- 2011
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Ingår i: ACM TRANSACTIONS ON THE WEB. - : ASSOC COMPUTING MACHINERY. - 1559-1131 .- 1559-114X. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Video sharing services that allow ordinary Web users to upload video clips of their choice and watch video clips uploaded by others have recently become very popular. This article identifies invariants in video sharing workloads, through comparison of the workload characteristics of four popular video sharing services. Our traces contain metadata on approximately 1.8 million videos which together have been viewed approximately 6 billion times. Using these traces, we study the similarities and differences in use of several Web 2.0 features such as ratings, comments, favorites, and propensity of uploading content. In general, we find that active contribution, such as video uploading and rating of videos, is much less prevalent than passive use. While uploaders in general are skewed with respect to the number of videos they upload, the fraction of multi-time uploaders is found to differ by a factor of two between two of the sites. The distributions of lifetime measures of video popularity are found to have heavy-tailed forms that are similar across the four sites. Finally, we consider implications for system design of the identified invariants. To gain further insight into caching in video sharing systems, and the relevance to caching of lifetime popularity measures, we gathered an additional dataset tracking views to a set of approximately 1.3 million videos from one of the services, over a twelve-week period. We find that lifetime popularity measures have some relevance for large cache (hot set) sizes (i.e., a hot set defined according to one of these measures is indeed relatively "hot"), but that this relevance substantially decreases as cache size decreases, owing to churn in video popularity.
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| 7. |
- Pasche, Boris, et al.
(författare)
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Somatic acquisition and signaling of TGFBR1*6A in cancer
- 2005
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 294:13, s. 1634-1646
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Tidskriftsartikel (refereegranskat)abstract
- Context: TGFBR1*6A is a common polymorphism of the type I transforming growth factor 0 receptor (TGFBR1). Epidemiological studies suggest that TGFBR1*6A may act as a tumor susceptibility allele. How TGFBR1*6A contributes to cancer development is largely unknown.. Objectives: To determine whether TGFBR1*6A is somatically acquired by primary tumors and metastases during cancer development and whether the 3-amino acid deletion that differentiates TGFBR1*6A from TGFBR1 is part of the mature receptor or part of the signal sequence and to investigate TGFBR1*6A signaling in cancer cells. Design, Setting, and Patients: Tumor And germline tissues from 531 patients with a diagnosis of head and neck, colorectal, or breast cancer recruited from 3 centers in the United States and from 1 center in Spain from June 1, 1994, through June 30, 2004, In vitro translation assays, MCF-7 breast cancer cells stably transfected with TGFBR1*6A, TGFBR1, or the vector alone, DLD-1 colorectal cancer cells that endogenously carry TGFBR1*6A, and SW48 colorectal cancer cells that do not carry TGFBR1*6A. Main Outcome Measures: TGFBR1*6A somatic acquisition in cancer. Determination of the amino terminus of the mature TGFBR1*6A and TGFBR1 receptors. Determination of TGF-beta-dependent cell proliferation. Results: TGFBR1*6A was somatically acquired in 13 of 44 (29.5%) colorectal cancer metastases, in 4 of 157 (2.5%) of colorectal tumors, in 4 of 226 (1.8%) head and neck primary tumors, and in none of the 104 patients with breast cancer. TGFBR1*6A somatic acquisition is not associated with loss of heterozygosity, microsatellite instability, or a mutator phenotype. The signal sequences of TGFBR1 and TGFBR1*6A are cleaved at the same site resulting in identical mature receptors. TGFBR1*6A may switch TGF-beta growth inhibitory signals into growth stimulatory signals in MCF-7 breast cancer cells and in DLD-1 colorectal cancer cells. Conclusions: TGFBR1*6A is somatically acquired in 29.5% of liver metastases from colorectal cancer and may bestow cancer cells with a growth advantage in the presence of TGF-beta. The functional consequences of this conversion appear to be mediated by the TGFBR1*6A signal sequence rather than by the mature receptor. The results highlight a new facet of TGF-beta signaling in cancer and suggest that TGFBR1*6A may represent a potential therapeutic target in cancer.
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