Integer Linear Programming for Sequence Problems: A general approach to reduce the problem size

Sequence problems belong to the most challenging interdisciplinary topics of the actuality. They are ubiquitous in science and daily life and occur, for example, in form of DNA sequences encoding all information of an organism, as a text (natural or formal) or in form of a computer program. Therefore, sequence problems occur in many variations in computational biology (drug development), coding theory, data compression, quantitative and computational linguistics (e.g. machine translation). In recent years appeared some proposals to formulate sequence problems like the closest string problem (CSP) and the farthest string problem (FSP) as an Integer Linear Programming Problem (ILPP). In the present talk we present a general novel approach to reduce the size of the ILPP by grouping isomorphous columns of the string matrix together. The approach is of practical use, since the solution of sequence problems is very time consuming, in particular when the sequences are long.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Phoneme Frequencies in Slovene (Text vs. Dictionary)

In this paper Slovene phoneme frequencies from a Slovene–German learner’s dictionary are analysed. The structure of the dictionary allows the determination of phoneme frequencies on two distinct linguistic levels: the level of dictionary (analysis of headwords) and the level of text (example sentences, illustrating a prototypical context of a given headword). By applying various statistical significance tests it can be shown that no significant differences between the rank-frequency distributions are observable. The same holds true for testing the differences, based on the repetition rate of phoneme frequencies on the dictionary and text levels. In contrast to this, only dichotomised data (by grouping them into vowels and consonants) show a significantly different frequency behaviour. Overall it can be shown that based on the given empirical observations, the conceptual importance and relevance of the levels of dictionary vs. text for quantitative phoneme studies has to be reconsidered and critically reflected in future studies

A functional yeast survival screen of tumor-derived cDNA libraries designed to identify anti-apoptotic mammalian oncogenes

Yeast cells can be killed upon expression of pro-apoptotic mammalian proteins. We have established a functional yeast survival screen that was used to isolate novel human anti-apoptotic genes overexpressed in treatment-resistant tumors. The screening of three different cDNA libraries prepared from metastatic melanoma, glioblastomas and leukemic blasts allowed for the identification of many yeast cell death-repressing cDNAs, including 28% of genes that are already known to inhibit apoptosis, 35% of genes upregulated in at least one tumor entity and 16% of genes described as both anti-apoptotic in function and upregulated in tumors. These results confirm the great potential of this screening tool to identify novel anti-apoptotic and tumor-relevant molecules. Three of the isolated candidate genes were further analyzed regarding their anti-apoptotic function in cell culture and their potential as a therapeutic target for molecular therapy. PAICS, an enzyme required for de novo purine biosynthesis, the long non-coding RNA MALAT1 and the MAST2 kinase are overexpressed in certain tumor entities and capable of suppressing apoptosis in human cells. Using a subcutaneous xenograft mouse model, we also demonstrated that glioblastoma tumor growth requires MAST2 expression. An additional advantage of the yeast survival screen is its universal applicability. By using various inducible pro-apoptotic killer proteins and screening the appropriate cDNA library prepared from normal or pathologic tissue of interest, the survival screen can be used to identify apoptosis inhibitors in many different systems

Implementation of the Combined--Nonlinear Condensation Transformation

We discuss several applications of the recently proposed combined nonlinear-condensation transformation (CNCT) for the evaluation of slowly convergent, nonalternating series. These include certain statistical distributions which are of importance in linguistics, statistical-mechanics theory, and biophysics (statistical analysis of DNA sequences). We also discuss applications of the transformation in experimental mathematics, and we briefly expand on further applications in theoretical physics. Finally, we discuss a related Mathematica program for the computation of Lerch's transcendent.Comment: 23 pages, 1 table, 1 figure (Comput. Phys. Commun., in press

The CD95 Receptor: Apoptosis Revisited

CD95 is the quintessential death receptor and, when it is bound by ligand, cells undergo apoptosis. Recent evidence suggests, however, that CD95 mediates not only apoptosis but also diverse nonapoptotic functions depending on the tissue and the conditions

Patterns of antibody responses to nonviral cancer antigens in head and neck squamous cell carcinoma patients differ by human papillomavirus status

There have been hints that nonviral cancer antigens are differentially expressed in human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC). Antibody responses (AR) to cancer antigens may be used to indirectly determine cancer antigen expression in the tumor using a noninvasive and tissue-saving liquid biopsy. Here, we set out to characterize AR to a panel of nonviral cancer antigens in HPV-positive and HPV-negative HNSCC patients. A fluorescent microbead multiplex serology to 29 cancer antigens (16 cancer-testis antigens, 5 cancer-retina antigens and 8 oncogenes) and 29 HPV-antigens was performed in 382 HNSCC patients from five independent cohorts (153 HPV-positive and 209 HPV-negative). AR to any of the cancer antigens were found in 272/382 patients (72%). The ten most frequent AR were CT47, cTAGE5a, c-myc, LAGE-1, MAGE-A1, -A3, -A4, NY-ESO-1, SpanX-a1 and p53. AR to MAGE-A3, MAGE-A9 and p53 were found at significantly different prevalences by HPV status. An analysis of AR mean fluorescent intensity values uncovered remarkably different AR clusters by HPV status. To identify optimal antigen selections covering a maximum of patients with ≤10 AR, multiobjective optimization revealed distinct antigen selections by HPV status. We identified that AR to nonviral antigens differ by HPV status indicating differential antigen expression. Multiplex serology may be used to characterize antigen expression using serum or plasma as a tissue-sparing liquid biopsy. Cancer antigen panels should address the distinct antigen repertoire of HPV-positive and HPV-negative HNSCC

Lack of association between gene polymorphisms of Angiotensin converting enzyme, Nod-like receptor 1, Toll-like receptor 4, FAS/FASL and the presence of Helicobacter pylori-induced premalignant gastric lesions and gastric cancer in Caucasians

<p>Abstract</p> <p>Background</p> <p>Several polymorphisms of genes involved in the immunological recognition of <it>Helicobacter pylori </it>and regulating apoptosis and proliferation have been linked to gastric carcinogenesis, however reported data are partially conflicting. The aim of our study was to evaluate potential associations between the presence of gastric cancer (GC) and high risk atrophic gastritis (HRAG) and polymorphisms of genes encoding <it>Angiotensin converting enzyme </it>(<it>ACE</it>), <it>Nod-like receptor 1 </it>(<it>NOD1</it>), <it>Toll-like receptor 4 </it>(<it>TLR4</it>) and <it>FAS/FASL</it>.</p> <p>Methods</p> <p>Gene polymorphisms were analyzed in 574 subjects (GC: n = 114; HRAG: n = 222, controls: n = 238) of Caucasian origin. <it>ACE I/D </it>(rs4646994), <it>NOD1 796G>A </it>(rs5743336), <it>TLR4 3725G>C </it>(rs11536889), <it>FAS 1377G>A </it>(rs2234767), <it>FAS 670A>G </it>(rs1800682) and <it>FASL 844T>C </it>(rs763110) were genotyped by different PCR approaches and restriction fragment length polymorphism analysis.</p> <p>Results</p> <p>Frequencies of genotypes in our study are similar to the data reported on subjects of Caucasian ethnicity. There was a tendency for <it>NOD1 796G/G </it>genotype to be associated with increased risk of HRAG (62.4% <it>vs</it>. 54.5% in controls, <it>p </it>= 0.082). <it>FAS 670G/G </it>genotype was more frequent in HRAG when compared to controls, 23.9% and 17.2% respectively, however it failed to reach significance level (<it>p </it>= 0.077). We did not find any significant associations for all polymorphisms in relation to GC or HRAG. <it>NOD1 796G>A </it>and <it>TLR4 3725G>C </it>gene polymorphisms were also not associated with <it>Helicobacter pylori </it>infection.</p> <p>Conclusions</p> <p><it>ACE, NOD1, TRL4 </it>and <it>FAS/FASL </it>gene polymorphisms are not linked with gastric carcinogenesis in Caucasians, and therefore they should not be considered as potential biomarkers for identifying individuals with higher risk for GC.</p

Probability theory and statistical applications: a profound treatise for self-study

This accessible and easy-to-read book provides many examples to illustrate diverse topics in probability and statistics, from initial concepts up to advanced calculations. Special attention is devoted e.g. to independency of events, inequalities in probability and functions of random variables. The book is directed to students of mathematics, statistics, engineering, and other quantitative sciences

Statistical simulation and the distribution of distances between identical elements in a random sequence

We study the distributions of distances between identical elements of a random sequence (e.g. a sequence of coin tosses or die tosses). We provide methods to generate observations by means of a statistical simulation and show in particular that distributions of multiple distances obey a linear or geometric (mixture) probability model, respectively. The results are useful to discover certain structures in texts or other information strings.Distribution of distances in sequences Statistical simulation MCMC Zipf's law Power laws Quantitative linguistics Burstiness

Frekvenca fonemov v slovenščini (besedilo in slovar)

In this paper Slovene phoneme frequencies from a Slovene–German learner’s dictionary are analysed. The structure of the dictionary allows the determination of phoneme frequencies on two distinct linguistic levels: the level of dictionary (analysis of headwords) and the level of text (example sentences, illustrating a prototypical context of a given headword). By applying various statistical significance tests it can be shown that no significant differences between the rank-frequency distributions are observable. The same holds true for testing the differences, based on the repetition rate of phoneme frequencies on the dictionary and text levels. In contrast to this, only dichotomised data (by grouping them into vowels and consonants) show a significantly different frequency behaviour. Overall it can be shown that based on the given empirical observations, the conceptual importance and relevance of the levels of dictionary vs. text for quantitative phoneme studies has to be reconsidered and critically reflected in future studies.V članku so analizirane frekvence slovenskih fonemov iz slovensko-nemškega tematskega (učnega) slovarja. Struktura slovarja omogoča ugotavljanje pogostosti fonemov na dveh različnih jezikovnih ravneh: na ravni slovarja (analiza gesel) in na ravni besedila (povedi, ki ponazarjajo prototipni kontekst določenega gesla). Z uporabo različnih statističnih testov pomembnosti je mogoče dokazati, da ni opaziti bistvenih razlik med porazdelitvami rangov pogostosti fonemov na ravni slovarja in besedila. Isto velja tudi za analizo glede stopnje ponavljanja fonemov. V nasprotju s tem dihotomizirani podatki (z razvrstitvijo v skupine na samoglasnike in soglasnike) pa vendarle kažejo bistveno drugačno »obnašanje« frekvenc. Na splošno je mogoče pokazati, da je za kvantitativne študije fonemov treba preučiti in kritično reflektirati konceptualno sicer zelo važno razliko med slovarjem in besedilom