Mathematical modeling to elucidate brain tumor abrogation by immunotherapy with T11 target structure

T11 Target structure (T11TS), a membrane glycoprotein isolated from sheep erythrocytes, reverses the immune suppressed state of brain tumor induced animals by boosting the functional status of the immune cells. This study aims at aiding in the design of more efficacious brain tumor therapies with T11 target structure. We propose a mathematical model for brain tumor (glioma) and the immune system interactions, which aims in designing efficacious brain tumor therapy. The model encompasses considerations of the interactive dynamics of macrophages, cytotoxic T lymphocytes, glioma cells, TGF-$\beta$, IFN-$\gamma$ and the T11TS. The system undergoes sensitivity analysis, that determines which state variables are sensitive to the given parameters and the parameters are estimated from the published data. Computer simulations were used for model verification and validation, which highlight the importance of T11 target structure in brain tumor therapy

Two-pronged attack: dual inhibition of Plasmodium falciparum M1 and M17 metalloaminopeptidases by a novel series of hydroxamic acid-based inhibitors

Plasmodium parasites, the causative agents of malaria, have developed resistance to most of our current antimalarial therapies, including artemisinin combination therapies which are widely described as our last line of defense. Antimalarial agents with a novel mode of action are urgently required. Two Plasmodium falciparum aminopeptidases, PfA-M1 and PfA-M17, play crucial roles in the erythrocytic stage of infection and have been validated as potential antimalarial targets. Using compound-bound crystal structures of both enzymes, we have used a structure-guided approach to develop a novel series of inhibitors capable of potent inhibition of both PfA-M1 and PfA-M17 activity and parasite growth in culture. Herein we describe the design, synthesis, and evaluation of a series of hydroxamic acid-based inhibitors and demonstrate the compounds to be exciting new leads for the development of novel antimalarial therapeutics

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Self-assembly and multifunctionality of peptide organogels: oil spill recovery, dye absorption and synthesis of conducting biomaterials

The self-assembly of a series of low molecular weight gelator dipeptides containing para amino benzoic acid has been studied in mechanistic detail.</p

A Rare Case Report of Siblings with Infantile and Late Infantile Forms of Neuronal Ceroid Lipofuscinoses

Neuronal Ceroid Lipofuscinoses is a neurodegenerative disorder predominantly involving grey matter. The 4 classic forms are Infantile type, Late Infantile type, Juvenile type and Adult type. We present a case of 3 siblings of unrelated parents where the eldest had Infantile form of NCL, the second child had Late Infantile Form, and the third child is normal. Both children having different phenotypic presentations have curvilinear inclusion bodies on EM of axillary skin biopsy, low levels of tripeptidyl amino peptidase 1(TPP1) and normal levels of palmitoyl protein thioesterase 1(PPT1), a finding classically present in the Late Infantile variety involving CLN2 mutation. After extensive search we failed to find a case report describing a similar finding. DOI: http://dx.doi.org/10.3126/jnps.v33i3.7924   J. Nepal Paediatr. Soc. 2013;33(3):220-222  </jats:p