An ontology for carcinoma classification for clinical bioinformatics

There are a number of existing classifications and staging schemes for carcinomas, one of the most frequently used being the TNM classification. Such classifications represent classes of entities which exist at various anatomical levels of granularity. We argue that in order to apply such representations to the Electronic Health Records one needs sound ontologies which take into consideration the diversity of the domains which are involved in clinical bioinformatics. Here we outline a formal theory for addressing these issues in a way that the ontologies can be used to support inferences relating to entities which exist at different anatomical levels of granularity. Our case study is the colon carcinoma, one of the most common carcinomas prevalent within the European population

Strain prioritization and genome mining for enediyne natural products

The enediyne family of natural products has had a profound impact on modern chemistry, biology, and medicine, and yet only 11 enediynes have been structurally characterized to date. Here we report a genome survey of 3,400 actinomycetes, identifying 81 strains that harbor genes encoding the enediyne polyketide synthase cassettes that could be grouped into 28 distinct clades based on phylogenetic analysis. Genome sequencing of 31 representative strains confirmed that each clade harbors a distinct enediyne biosynthetic gene cluster. A genome neighborhood network allows prediction of new structural features and biosynthetic insights that could be exploited for enediyne discovery. We confirmed one clade as new C-1027 producers, with a significantly higher C-1027 titer than the original producer, and discovered a new family of enediyne natural products, the tiancimycins (TNMs), that exhibit potent cytotoxicity against a broad spectrum of cancer cell lines. Our results demonstrate the feasibility of rapid discovery of new enediynes from a large strain collection. IMPORTANCE Recent advances in microbial genomics clearly revealed that the biosynthetic potential of soil actinomycetes to produce enediynes is underappreciated. A great challenge is to develop innovative methods to discover new enediynes and produce them in sufficient quantities for chemical, biological, and clinical investigations. This work demonstrated the feasibility of rapid discovery of new enediynes from a large strain collection. The new C-1027 producers, with a significantly higher C-1027 titer than the original producer, will impact the practical supply of this important drug lead. The TNMs, with their extremely potent cytotoxicity against various cancer cells and their rapid and complete cancer cell killing characteristics, in comparison with the payloads used in FDA-approved antibody-drug conjugates (ADCs), are poised to be exploited as payload candidates for the next generation of anticancer ADCs. Follow-up studies on the other identified hits promise the discovery of new enediynes, radically expanding the chemical space for the enediyne family

Incompressible Turbulence as Nonlocal Field Theory

It is well known that incompressible turbulence is nonlocal in real space because sound speed is infinite in incompressible fluids. The equation in Fourier space indicates that it is nonlocal in Fourier space as well. Contrast this with Burgers equation which is local in real space. Note that the sound speed in Burgers equation is zero. In our presentation we will contrast these two equations using nonlocal field theory. Energy spectrum and renormalized parameters will be discussed.Comment: 7 pages; Talk presented in Conference on "Perspectives in Nonlinear Dynamics (PNLD 2004)" held in Chennai, 200

Using of Binominal Method for the Purpose of Determination of Confidence Intervals for Prediction of Invasive Ductal Breast Carcinoma Metastases

The study was performed using surgical and biopsy material based on histopathological study, which was conducted at the Chernivtsy Regional Clinical Oncology Centre. In the cases of verified diagnosis of ductal breast carcinoma was studied the size of the primary tumour node and metastasis in lymphogenous features of regional lymph node according to classification system TNM. All cases were divided by categories T and N. Using statistical data was conducted the analysis in patients of verified diagnosis of ductal breast carcinoma in Chernivtsy region. We determined the features of metastasis to regional lymph nodes under according to the classification pTNM and confidence intervals calculated according to percent binomial method with p=0.05. After receiving the results the data were compared to predict metastasis. Using statistical data were conducted the analysis in women of Chernivtsi region with verified diagnosis of ductal breast cancer. We determined the features of metastasis classification according pTNM and confidence intervals of percent according to binominal method with p=0.05. All observations of histopathological conclusions were conducted on the basis of Chernivtsy Regional Clinical Oncology Centre

On the critical point of the Random Walk Pinning Model in dimension d=3

We consider the Random Walk Pinning Model studied in [3,2]: this is a random walk X on Z^d, whose law is modified by the exponential of \beta times L_N(X,Y), the collision local time up to time N with the (quenched) trajectory Y of another d-dimensional random walk. If \beta exceeds a certain critical value \beta_c, the two walks stick together for typical Y realizations (localized phase). A natural question is whether the disorder is relevant or not, that is whether the quenched and annealed systems have the same critical behavior. Birkner and Sun proved that \beta_c coincides with the critical point of the annealed Random Walk Pinning Model if the space dimension is d=1 or d=2, and that it differs from it in dimension d\ge4 (for d\ge 5, the result was proven also in [2]). Here, we consider the open case of the marginal dimension d=3, and we prove non-coincidence of the critical points.Comment: 23 pages; v2: added reference [4], where a result similar to Th. 2.8 is proven independently for the continuous-time mode