Enhanced Dark Block Extraction Method Performed Automatically to Determine the Number of Clusters in Unlabeled Data Sets

One of the major issues in data cluster analysis is to decide the number of clusters or groups from a set of unlabeled data. In addition, the presentation of cluster should be analyzed to provide the accuracy of clustering objects. This paper propose a new method called Enhanced-Dark Block Extraction (E-DBE), which automatically identifies the number of objects groups in unlabeled datasets. The proposed algorithm relies on the available algorithm for visual assessment of cluster tendency of a dataset, by using several common signal and image processing techniques. The method includes the following steps: 1.Generating an Enhanced Visual Assessment Tendency (E-VAT) image from a dissimilarity matrix which is the input for E-DBE algorithm. 2. Processing image segmentation on E-VAT image to obtain a binary image then performs filter techniques. 3. Performing distance transformation to the filtered binary image and projecting the pixels in the main diagonal alignment of the image to figure a projection signal. 4. Smoothing the outcrop signal, computing its first-order derivative and then detecting major peaks and valleys in the resulting signal to acquire the number of clusters. E-DBE is a parameter-free algorithm to perform cluster analysis. Experiments of the method are presented on several UCI, synthetic and real world datasets

A Review on Plant-Derived Immunomodulatory Agents: Hopes as an Alternative Medicine in the Management of Immune-Related Disorders

In humans, the immune system serves as a protective barrier against infection; however, when the immune system is out of balance, it can harm the host. Immunomodulators are chemicals or medications that have been employed in the clinic to treat an unbalanced immune response. The majority of immunological medicines in clinical use are cytotoxic. They harm the patient's quality of life by causing various side effects and being associated with higher production costs, longer lead times, and a high failure rate. Furthermore, obtaining single-compound chemicals with low toxicity, high efficacy, and selectivity for specified disorders is difficult for researchers. As a result, techniques based on alternative medicine are gaining traction in drug development, focusing on innovative natural compounds utilized to treat various disorders. Many plant molecules founded to have biologically beneficial properties. This review aimed to look at the immunomodulatory activity of plant-derived chemicals from widely used plants that treat a range of diseases worldwide

Eradication of large solid tumors by gene therapy with a T cell receptor targeting a single cancer-specific point mutation

PURPOSE: Cancers usually contain multiple unique tumor-specific antigens produced by single amino acid substitutions (AAS) and encoded by somatic non-synonymous single nucleotide substitutions. We determined whether adoptively transferred T cells can reject large, well-established solid tumors when engineered to express a single type of T cell receptor (TCR) that is specific for a single AAS. EXPERIMENTAL DESIGN: By exome and RNA sequencing of an UV-induced tumor, we identified an AAS in p68 (mp68), a co-activator of p53. This AAS seemed to be an ideal tumor-specific neoepitope because it is encoded by a trunk mutation in the primary autochthonous cancer and binds with highest affinity to the MHC. A high-avidity mp68-specific TCR was used to genetically engineer T cells as well as to generate TCR-transgenic mice for adoptive therapy. RESULTS: When the neoepitope was expressed at high levels and by all cancer cells, their direct recognition sufficed to destroy intra-tumor vessels and eradicate large, long-established solid tumors. When the neoepitope was targeted as autochthonous antigen, T cells caused cancer regression followed by escape of antigen-negative variants. Escape could be thwarted by expressing the antigen at increased levels in all cancer cells or by combining T cell therapy with local irradiation. Therapeutic efficacies of TCR-transduced and TCR-transgenic T cells were similar. CONCLUSIONS: Gene therapy with a single TCR targeting a single AAS can eradicate large established cancer but a uniform expression and/or sufficient levels of the targeted neoepitope or additional therapy are required to overcome tumor escape

Exercise therapy in adults with serious mental illness: a systematic review and meta-analysis

Background: Individuals with serious mental illness are at a higher risk of physical ill health. Mortality rates are at least twice those of the general population with higher levels of cardiovascular disease, metabolic disease, diabetes, and respiratory illness. Although genetics may have a role in the physical health problems of these patients, lifestyle and environmental factors such as levels of smoking, obesity, poor diet, and low levels of physical activity also play a prominent part.<p></p> Objective: To conduct a systematic review and meta-analysis of randomised controlled trials comparing the effect of exercise interventions on individuals with serious mental illness.<p></p> Methods: Searches were made in Ovid MEDLINE, Embase, CINAHL, PsycINFO, Biological Abstracts on Ovid, and The Cochrane Library (January 2009, repeated January 2013) through to February 2013.<p></p> Results: Eight RCTs were identified in the systematic search. Six compared exercise versus usual care. One study assessed the effect of a cycling programme versus muscle strengthening and toning exercises. The final study compared the effect of adding specific exercise advice and motivational skills to a simple walking programme. Exercise programmes were noted by their heterogeneity in terms of the type of exercise intervention, setting, and outcome measures. The review found that exercise improved levels of exercise activity (n=13, standard mean difference [SMD] 1.81, CI 0.44 to 3.18, p = 0.01). No beneficial effect was found on negative (n = 84, SMD = -0.54, CI -1.79 to 0.71, p = 0.40) or positive symptoms of schizophrenia (n = 84, SMD = -1.66, CI -3.78 to 0.45, p = 0.12). No change was found on body mass index compared with usual care (n= 151, SMD = -0.24, CI -0.56 to 0.08, p = 0.14), or body weight (n = 77, SMD = 0.13, CI -0.32 to 0.58, p = 0.57). No beneficial effect was found on anxiety and depressive symptoms (n = 94, SMD = -0.26, CI -0.91 to 0.39, p = 0.43), or quality of life in respect of physical and mental domains. One RCT measured the effect of exercise on exercise intensity, attendance, and persistence at a programme. No significant effect was found on these measures.<p></p> Conclusions: This systematic review showed that exercise therapies can lead to a modest increase in levels of exercise activity but overall there was no noticeable change for symptoms of mental health, body mass index, and body weight.<p></p&gt

Immunogenicity and Efficacy of Single Antigen Gp63, Polytope and PolytopeHSP70 DNA Vaccines against Visceral Leishmaniasis in Experimental Mouse Model

Polytope approach of genetic immunization is a promising strategy for the prevention of infectious disease as it is capable of generating effective cell mediated immunity by delivering the T cell epitopes assembled in series. Leishmaniasis is a significant world wide health problem for which no vaccine exists. In this study we have compared immunogenicity and efficacy of three types of DNA vaccines: single antigen Gp63 (Gp63/pcDNA), polytope (Poly/pcDNA) and Polytope fused with hsp70 (Poly/hsp/pcDNA) against visceral leishmaniasis in susceptible BALB/c mice. Mice vaccinated with these plasmids generated strong Th1 immune response as seen by dominating IFN-γ over IL-10 cytokine. Interestingly, cytotoxic responses generated by polytope DNA plasmid fused with hsp70 of Leishmania donovani were significantly higher when compared to polytope and single antigen Gp63 vaccine. Challenge studies revealed that the parasite load in liver and spleen was significantly lower with Poly/hsp/pcDNA vaccination compared to other vaccines. Therefore, our study indicates that polytope DNA vaccine is a feasible, practical and effective approach for visceral leishmaniasis