Tumor taxonomy for the developmental lineage classification of neoplasms

BACKGROUND: The new "Developmental lineage classification of neoplasms" was described in a prior publication. The classification is simple (the entire hierarchy is described with just 39 classifiers), comprehensive (providing a place for every tumor of man), and consistent with recent attempts to characterize tumors by cytogenetic and molecular features. A taxonomy is a list of the instances that populate a classification. The taxonomy of neoplasia attempts to list every known term for every known tumor of man. METHODS: The taxonomy provides each concept with a unique code and groups synonymous terms under the same concept. A Perl script validated successive drafts of the taxonomy ensuring that: 1) each term occurs only once in the taxonomy; 2) each term occurs in only one tumor class; 3) each concept code occurs in one and only one hierarchical position in the classification; and 4) the file containing the classification and taxonomy is a well-formed XML (eXtensible Markup Language) document. RESULTS: The taxonomy currently contains 122,632 different terms encompassing 5,376 neoplasm concepts. Each concept has, on average, 23 synonyms. The taxonomy populates "The developmental lineage classification of neoplasms," and is available as an XML file, currently 9+ Megabytes in length. A representation of the classification/taxonomy listing each term followed by its code, followed by its full ancestry, is available as a flat-file, 19+ Megabytes in length. The taxonomy is the largest nomenclature of neoplasms, with more than twice the number of neoplasm names found in other medical nomenclatures, including the 2004 version of the Unified Medical Language System, the Systematized Nomenclature of Medicine Clinical Terminology, the National Cancer Institute's Thesaurus, and the International Classification of Diseases Oncolology version. CONCLUSIONS: This manuscript describes a comprehensive taxonomy of neoplasia that collects synonymous terms under a unique code number and assigns each tumor to a single class within the tumor hierarchy. The entire classification and taxonomy are available as open access files (in XML and flat-file formats) with this article

Self-amplified Cherenkov radiation from a relativistic electron in a waveguide partially filled with a laminated material

The radiation from a relativistic electron uniformly moving along the axis of cylindrical waveguide filled with laminated material of finite length is investigated. Expressions for the spectral distribution of radiation passing throw the transverse section of waveguide at large distances from the laminated material are derived with no limitations on the amplitude and variation profile of the layered medium permittivity and permeability. Numerical results for layered material consisting of dielectric plates alternated with vacuum gaps are given. It is shown that at a special choice of problem parameters, Cherenkov radiation generated by the relativistic electron inside the plates is self-amplified. The visual explanation of this effect is given and a possible application is discussed.Comment: 8 pages, 4 figures,1 table, the paper is accepted for publication in the Journal of Physics: Conference Serie

Elastic and Raman scattering of 9.0 and 11.4 MeV photons from Au, Dy and In

Monoenergetic photons between 8.8 and 11.4 MeV were scattered elastically and in elastically (Raman) from natural targets of Au, Dy and In.15 new cross sections were measured. Evidence is presented for a slight deformation in the 197Au nucleus, generally believed to be spherical. It is predicted, on the basis of these measurements, that the Giant Dipole Resonance of Dy is very similar to that of 160Gd. A narrow isolated resonance at 9.0 MeV is observed in In.Comment: 31 pages, 11 figure

Quantum Revivals in Periodically Driven Systems close to nonlinear resonance

We calculate the quantum revival time for a wave-packet initially well localized in a one-dimensional potential in the presence of an external periodic modulating field. The dependence of the revival time on various parameters of the driven system is shown analytically. As an example of application of our approach, we compare the analytically obtained values of the revival time for various modulation strengths with the numerically computed ones in the case of a driven gravitational cavity. We show that they are in very good agreement.Comment: 14 pages, 1 figur

Compromised BRCA1-PALB2 interaction is associated with breast cancer risk.

The major breast cancer suppressor proteins BRCA1 and BRCA2 play essential roles in homologous recombination (HR)-mediated DNA repair, which is thought to be critical for tumor suppression. The two BRCA proteins are linked by a third tumor suppressor, PALB2, in the HR pathway. While truncating mutations in these genes are generally pathogenic, interpretation of missense variants remains a challenge. To date, patient-derived missense variants that disrupt PALB2 binding have been identified in BRCA1 and BRCA2; however, there has not been sufficient evidence to prove their pathogenicity in humans, and no variants in PALB2 that disrupt either its BRCA1 or BRCA2 binding have been reported. Here we report on the identification of a novel PALB2 variant, c.104T>C (p.L35P), that segregates in a family with a strong history of breast cancer. Functional analyses showed that L35P abrogates the PALB2-BRCA1 interaction and completely disables its abilities to promote HR and confer resistance to platinum salts and PARP inhibitors. Whole-exome sequencing of a breast cancer from a c.104T>C carrier revealed a second, somatic, truncating mutation affecting PALB2, and the tumor displays hallmark genomic features of tumors with BRCA mutations and HR defects, cementing the pathogenicity of L35P. Parallel analyses of other germline variants in the PALB2 N-terminal BRCA1-binding domain identified multiple variants that affect HR function to varying degrees, suggesting their possible contribution to cancer development. Our findings establish L35P as the first pathogenic missense mutation in PALB2 and directly demonstrate the requirement of the PALB2-BRCA1 interaction for breast cancer suppression

Channeling of Positrons through Periodically Bent Crystals: on Feasibility of Crystalline Undulator and Gamma-Laser

The electromagnetic radiation generated by ultra-relativistic positrons channelling in a crystalline undulator is discussed. The crystalline undulator is a crystal whose planes are bent periodically with the amplitude much larger than the interplanar spacing. Various conditions and criteria to be fulfilled for the crystalline undulator operation are established. Different methods of the crystal bending are described. We present the results of numeric calculations of spectral distributions of the spontaneous radiation emitted in the crystalline undulator and discuss the possibility to create the stimulated emission in such a system in analogy with the free electron laser. A careful literature survey covering the formulation of all essential ideas in this field is given. Our investigation shows that the proposed mechanism provides an efficient source for high energy photons, which is worth to study experimentally.Comment: 52 pages, MikTeX, 14 figure

Structure-based statistical analysis of transmembrane helices

Recent advances in determination of the high-resolution structure of membrane proteins now enable analysis of the main features of amino acids in transmembrane (TM) segments in comparison with amino acids in water-soluble helices. In this work, we conducted a large-scale analysis of the prevalent locations of amino acids by using a data set of 170 structures of integral membrane proteins obtained from the MPtopo database and 930 structures of water-soluble helical proteins obtained from the protein data bank. Large hydrophobic amino acids (Leu, Val, Ile, and Phe) plus Gly were clearly prevalent in TM helices whereas polar amino acids (Glu, Lys, Asp, Arg, and Gln) were less frequent in this type of helix. The distribution of amino acids along TM helices was also examined. As expected, hydrophobic and slightly polar amino acids are commonly found in the hydrophobic core of the membrane whereas aromatic (Trp and Tyr), Pro, and the hydrophilic amino acids (Asn, His, and Gln) occur more frequently in the interface regions. Charged amino acids are also statistically prevalent outside the hydrophobic core of the membrane, and whereas acidic amino acids are frequently found at both cytoplasmic and extra-cytoplasmic interfaces, basic amino acids cluster at the cytoplasmic interface. These results strongly support the experimentally demonstrated biased distribution of positively charged amino acids (that is, the so-called the positive-inside rule) with structural data