Functional role of Toll-like receptor-7 in experimental lupus nephritis

Die vorliegende Studie trägt zum besseren Verständnis des breiten klinischen Spektrums und des Fehlens universeller Serum- Marker der infektionsassoziierten Krankheitsaktivität der Lupus- Nephritis und möglicherweise anderer Formen der Immunkomplexnephritis bei. Exogener Kontakt mit TLR 7- Liganden hat die Entwicklung der Lupus- Nephritis bei jungen, gesunden MRL- Wildtyp und MRLlpr/lpr Mäusen nicht getriggert und hatte keinen signifikanten Effekt auf die Krankheitsaktivität bei diesen jungen Mäusen. Bei alten Lupus- Mäusen führte eine ähnliche Exposition jedoch zu einem merklichen Anstieg der Serumspiegel proinflammatorischer Zytokine und von IFNα, sowie zu einer Infiltration der Nierenglomeruli 18 Wochen alter MRLlpr/lpr Mäuse mit Makrophagen und einer (nicht signifikanten) Erhöhung der Autoantikörperspiegel. Diese Daten unterstützen die Theorie, dass dem Toll- like Rezeptor 7 eine Rolle bei den Mechanismen, die das Fortschreiten der autoimmunen Gewebsschädigung in MRLlpr/lpr Mäusen fördern, zukommt. Basierend auf den Ergebnissen der funktionellen Rolle von TLR 7 in Lupus- Mäusen und in Primärzellen, die aus Lupusmäusen isoliert wurden, sahen wir in der TLR 7- Blockade ein mögliches neues Ziel, um die schädlichen Effekte des Signalings über Immunkomplexe und endogene Liganden zu begrenzen. Es zeigte sich, dass die Blockade von TLR 7 und TLR 7 + TLR 9 die Gewebsschäden in Nieren und Lunge signifikant reduzieren konnte. Eine TLR 7 Antagonisierung mit dem Oligodeoxyribonukleotid IRS661 senkte die Menge an Autoantikörpern (insbesondere anti- SM, anti- dsDNA, IgG2a, IgG2b), entzündlichen Zytokine und Chemokinen im Serum, glomerulären Ablagerungen von IgG2a und Komplementfaktor C3c deutlich. Die Hemmung von TLR 7 reduzierte ebenfalls die CC- Chemokin- gesteuerten Makrophagen- und T- Zell- Infiltrate in den Nieren. Dies zeigte sich durch erniedrigte Spiegel von Ccr2, Ccr5, Ccl2 und Ccl5 in den Nieren behandelter Tiere. Diese Ergebnisse unterstützen das Konzept, dass endogene TLR 7- Liganden zur Pathogenese der Autoantikörperproduktion und der autoimmun vermittelten Gewebsschädigung des SLE beitragen. Die TLR 7- Blockade könnte ein neues therapeutisches Konzept beim Lupus erythematodes sein.In summary, exogenous administration of Tlr7 ligand in young, healthy MRL-wild type and MRLlpr/lpr mice did not trigger the development of lupus nephritis, and did not have any significant effect on disease activity. Upon similar exposure in well established lupus produced marked increase in serum levels of proinflammatory cytokines and IFN, infiltration of macrophages in glomeruli of kidneys of 18 weeks old MRLlpr/lpr mice and trend towards increased autoantibodies level. These data support a role of Tlr7 for the mechanisms that foster the progression of autoimmune tissue injury in MRLlpr/lpr mice. Hence these studies might suggest that TLR7 is an adjuvant amplification factor rather than a causative factor for autoimmunity. Based on the results of functional role of Tlr7 in lupus mice and the primary cells isolated from the lupus mice suggested a new potential target of blocking Tlr7 to restrict the harmful effects of its downstream signalling via the immune-complexes and endogenous ligands. The blockade of Tlr7 and dual blockade of Tlr7 & Tlr9 resulted in efficient and significant reduction of tissue injury in kidneys and lungs of lupus mice. Tlr7 antagonism with the oligodeoxyribonucleotide IRS661, significantly reduced the levels of autoantibodies (specifically anti-Sm, anti-dsDNA IgG2a, IgG2b), inflammatory cytokines, chemokines in serum, the glomerular deposits of IgG2a and complement factor C3c. Inhibition of Tlr7 also reduced CC-chemokine-driven macrophage and T cell infiltrates in kidneys as replicated by decreased levels of Ccr2 and Ccr5 and Ccl2 and Ccl5 in treated kidneys. These results support the concept that endogenous ligands of Tlr7 such as smRNP and RNA associated immune-complexes contribute to the pathogenesis of autoantibody production and autoimmune tissue injury in SLE and propose TLR7 blockade as a novel therapeutic target for lupus. Although the role of TLR7 in escape of B and T cells from the tolerance checkpoints to become self-reactive and loss of anergy needs to be studied in future

Molecular mechanisms of autoimmunity triggered by microbial infection

Autoimmunity can be triggered by microbial infection. In this context, the discovery of Toll-like receptors (TLRs) provides new insights and research perspectives. TLRs induce innate and adaptive antimicrobial immune responses upon exposure to common pathogen-associated molecules, including lipopeptides, lipopolysaccharides, and nucleic acids. They also have the potential, however, to trigger autoimmune disease, as has been revealed by an increasing number of experimental reports. This review summarizes important facts about TLR biology, available data on their role in autoimmunity, and potential consequences for the management of patients with autoimmune disease

Human Development Index (HDI): A Case study of Aasgaon Village, Dist- Satara, Maharashtra, India

The Human Development Index (HDI) is a summary composite index that measures average achievement of particular nation in three basic aspects of human development. These aspects are popularly known as (1) A long and healthy life. (2) Knowledge (3) A decent standard of living. This research paper focus on HDI of Aasgaon- a small & popular village of satara district of Maharashtra state, which is role model for rural development and self sufficiency. The village has achieved success because of its social transformation with the help & active participation of local people, especially women. Key words: HDI, Life expectancy index, Education index, Adult literacy index, Gross enrollment index, GDP index

Audio diarization for LENA data and its application to computing language behavior statistics for individuals with autism

The objective of this dissertation is to develop diarization algorithms for LENA data and study its application to compute language behavior statistics for individuals with autism. LENA device is one of the most commonly used devices to collect audio data in autism and language development studies. LENA child and adult detector algorithms were evaluated for two different datasets: i) older children dataset consisting of children already diagnosed with autism spectrum disor- der and ii) infants dataset consisting of infants at risk for autism. I-vector based diarization algorithms were developed for the two datasets to tackle two scenarios: a) some amount of labeled data is present for every speaker present in the audio recording and b) no labeled data is present for the audio recording to be diarized. Further, i-vector based diarization methods were applied to compute objective measures of assessment. These objective measures of assessment were analyzed to show they can reveal some aspects of autism severity. Also, a method to extract a 5 minute high child vocalization audio window from a 16 hour day long recording was developed, which was then used to compute canonical babble statistics using human annotation.Ph.D

Mobile Cloud Encrypted Searching and Traffic Reduction

Now days, cloud infrastructure have been popular for storing data in the world. User can store his public and private data on cloud. To secure the private data it must be encrypted. This encrypted data should be retrieved and stored efficiently. This era is digital era. Nearly about each person has mobile phone. So smart phone would be the best client for the cloud. But using smart phone use wireless network which face many difficulties like low bandwidth, low latency, low battery, low transmission etc. The traditional search is not developed on focusing on smart phone so using smart phone it require the extra network traffic and long time for search. The application use the light weight trapdoor which reduce trapdoor size and provide feasible method for the network traffic efficiency. Also it use and Ranked Serial Binary Search algorithm 0and Trapdoor Mapping Table (TMT) to minimize the search time. The proposed system reduce the search time and network traffic

Effect of vesicular encapsulation on in-vitro cytotoxicity of ciclopirox olamine

Context: Ciclopirox olamine (CPO), an antifungal has recently been cited as a drug repurposed for cancer treatment.  Vesicular drug delivery systems like liposomes and niosomes have proven to increase the efficacy of anticancer drugs. Objective: The purpose of this paper was to evaluate the effect of two vesicular delivery systems liposome and niosome on the anticancer potential of CPO using in vitro cytotoxicity assays. Materials and methods: CPO was encapsulated in liposomes (prepared from Phospholipon®90H) and niosomes (prepared from Span 60) by ethanol injection method.  The cytotoxic effect of liposomal and niosomal CPO was evaluated on KB (oral cancer), PC3 (prostate cancer), Siha (cervical cancer) and Vero (kidney epithelial) cell lines using MTT assay. The IC50 values were compared with free drug CPO and with standard anticancer drug doxorubicin Results: CPO exhibited cytotoxicity to all the cell lines studied. The niosomal encapsulation of CPO favored its cytotoxicity on the cancer cell lines. Much lower IC50 values were obtained in comparison to the liposomal and free form of CPO. The enhancement in the cytotoxic effect on the non-cancer cell line Vero was not noted. Discussion: CPO demonstrated marginal difference in the concentration required to produce cytotoxic effect on cancer and normal cell lines. The difference was enhanced by niosomal CPO as much lower concentration was required to produce cytotoxic effect on cancer cells while rendering no effect on normal cells. Conclusion: Enhanced cytotoxicity selectively to cancer cells in the present study demonstrates the pharmacological significance of niosomal drug delivery system of CPO

Survey on Leaf Disease Detection and Grading using Artificial Neural Network (ANN) and Fuzzy Logic

In Horticulture, leaf sicknesses have become a difficult as it can bring about noteworthy reduction in both quality what is more, amount of agrarian yields. Therefore, robotized acknowledgment of maladies on leaves assumes a vital part in farming segment. This paper bestows a straightforward and computationally capable strategy utilized for leaf infection distinguishing proof and reviewing utilizing advanced picture handling and machine vision innovation. The proposed framework is partitioned into two stages, in first stage the plant is perceived on the premise of the elements of leaf, it incorporates pre-handling of leaf pictures, and highlight extraction taken after by Counterfeit Neural System based preparing and arrangement for acknowledgment of leaf. In second stage the infection present in the leaf is arranged, this procedure incorporates K-Implies based division of abandoned range, highlight extraction of abandoned bit and the ANN based grouping of malady. At that point the infection reviewing is done on the premise of the measure of infection present in the leaf

A REVIEW: RAPID PROTOTYPING TECHNIQUES FOR DESIGNING AND MANUFACTURING OF CUSTOMIZED ANATOMICAL IMPLANTS

ABSTRACT Rapid prototyping (RP) technologies are mostly related with applications in the product development and the design process as well as with small batch manufacturing. Due to their comparatively high rapidity and flexibility, however, they have also been engaged in various nonmanufacturing applications. A field that attracts increasingly more attention by the scientific community is related to the application of technologies in medicine and health care. The associated research is focused both on the development of specifically customized or new methods and systems based on principles, as well as on the applications of existing systems assisting health care services. In this paper, representative case studies and research efforts from the field of medical applications are presented and discussed in detail. The case studies included cover applications like the fabrication of custom implants and scaffolds for rehabilitation, models for pre-operating surgical planning, anatomical models for the mechanical testing and investigation of human bones or of new medical techniques, drug delivery devices fabrication, as well as the development of new techniques specifically designed for medical applications

Sustainable Infrastructure Development: Integrating Environmental and Social Factors in Civil Engineering

In order to explore sustainable infrastructure development, this study uses a descriptive design, a deductive approach, as well as an interpretivist philosophy in civil engineering. The study examines the social, technical, and environmental effects as well as regulatory frameworks in the larger picture of sustainable projects using secondary data. The results show how social and environmental factors are intricately related, with a focus on community involvement, technology optimization, and the efficacy of regulations. Finding synergies and trade-offs through critical analysis informs recommendations for community-centric approaches, coordinated evaluation frameworks, and regulatory policy advancements. Prospective research demands investigating new technologies, long-term studies, as well as the socio-cultural aspects of sustainability. The study promotes resilience, inclusion, and environmental consciousness, adding to the growing conversation on sustainable civil engineering

Hoodigogenin A from Hoodia gordonii

The title mol­ecule (systematic name: 12-O-β-tigloyl-3β,14β-dihydroxy­pregn-5-en-20-one), C26H38O5, isolated from aerial parts of Hoodia gordonii, has its steroid A and C rings in chair conformations, its B ring in a half-chair conformation, and its five-membered ring in an envelope conformation. The OH group at the C/D ring junction forms an intra­molecular hydrogen bond with the keto substituent. The OH group on the A ring forms an inter­molecular hydrogen bond with the tiglate C=O group, propagating [010] chains in the crystal structure