RECQL4: linking DNA replication to bone tumorigenesis

RECQL4 is a gene that encodes a 1208 amino acid protein. RECQL4 protein is required during DNA replication initiation and DNA end resection. A lack of RECQL4 is therefore associated with a decrease in DNA damage repair. There are three unrelated autosomal recessive diseases that are linked with mutations in RECQL4. Rothmund Thomson Syndrome is rare disorder which has documented mutations within RECQL4 which has been linked to an increased tendency to develop osteosarcomas. To study the effect of RECQL4 depletion, shRNA knockdowns, ASC52Telo cells, osteodifferentiated cells and osteo-differentiated cells in long term PHA-767491 treatment were subjected to a series of experiments. The trilineage differentiation capability, growth characteristics, expression of cell proliferation and bone formation markers, drug sensitivity and chromosomal instability was tested for each of the cell lines. These results could be used to identify any differences in expressions and behaviours between the RECQL4 depleted cells and the control cells. All the cell lines were able to differentiate into adipocytes and osteoblasts, with p44 pLK0.1 and p44 shRQ-9 having a decreased adipocyte differentiation in comparison to the others. No significant difference was observed in the growth assay between the cells in which RECQL4 was depleted and their controls. The p44 shRQ-9 cells showed the lowest foci count when tested for 53BP expression but the highest Ki67 expression. There were no significant results between the RECQL4 depleted cells and their controls when looking at marker gene expressions. The drug sensitivity assays also show no significant differences however p14 shRQ-10 and P44 shRQ-10 appear less sensitive in the mid-range concentrations. The chromosomal analysis showed that OD+PHA, p44 shRQ-9 and p44 shRQ-10 have an increased degree of aneuploidy and tetraploid cells

Implications of Neutrino Mass Generation from QCD Confinement

We consider the possibility that the quark condensate formed by QCD confinement generates Majorana neutrino masses m_\nu via dimension seven operators. No degrees of freedom beyond the Standard Model are necessary, below the electroweak scale. Obtaining experimentally acceptable neutrino masses requires the new physics scale \Lambda ~ TeV, providing a new motivation for weak-scale discoveries at the LHC. We implement this mechanism using a Z_3 symmetry which leads to a massless up quark above the QCD chiral condensate scale. We use non-helicity-suppressed light meson rare decay data to constrain \Lambda. Experimental constraints place a mild hierarchy on the flavor structure of dimension seven operators and the resulting neutrino mass matrix.Comment: 4 pages, Revte

TeV Scale Singlet Dark Matter

It is well known that stable weak scale particles are viable dark matter candidates since the annihilation cross section is naturally about the right magnitude to leave the correct thermal residual abundance. Many dark matter searches have focused on relatively light dark matter consistent with weak couplings to the Standard Model. However, in a strongly coupled theory, or even if the coupling is just a few times bigger than the Standard Model couplings, dark matter can have TeV-scale mass with the correct thermal relic abundance. Here we consider neutral TeV-mass scalar dark matter, its necessary interactions, and potential signals. We consider signals both with and without higher-dimension operators generated by strong coupling at the TeV scale, as might happen for example in an RS scenario. We find some potential for detection in high energy photons that depends on the dark matter distribution. Detection in positrons at lower energies, such as those PAMELA probes, would be difficult though a higher energy positron signal could in principle be detectable over background. However, a light dark matter particle with higher-dimensional interactions consistent with a TeV cutoff can in principle match PAMELA data.Comment: 30 pages, 11 figures. Minor changes, references adde

Natural Neutrino Masses and Mixings from Warped Geometry

We demonstrate that flavor symmetries in warped geometry can provide a natural explanation for large mixing angles and economically explain the distinction between the quark and lepton flavor sectors. We show how to naturally generate Majorana neutrino masses assuming a gauged a U(1)_{B-L} symmetry broken in the UV that generates see-saw masses of the right size. This model requires lepton minimal flavor violation (LMFV) in which only Yukawa matrices (present on the IR brane) break the flavor symmetries. The symmetry-breaking is transmitted to charged lepton bulk mass parameters as well to generate the hierarchy of charged lepton masses. With LMFV, a GIM-like mechanism prevents dangerous flavor-changing processes for charged leptons and permits flavor-changing processes only in the presence of the neutrino Yukawa interaction and are therefore suppressed when the overall scale for the neutrino Yukawa matrix is slightly smaller than one in units of the curvature. In this case the theory can be consistent with a cutoff of 10 TeV and 3 TeV Kaluza-Klein masses.Comment: 18 pages, 3 figures, to match with published versio

Phenomenological Implications of Deflected Mirage Mediation: Comparison with Mirage Mediation

We compare the collider phenomenology of mirage mediation and deflected mirage mediation, which are two recently proposed "mixed" supersymmetry breaking scenarios motivated from string compactifications. The scenarios differ in that deflected mirage mediation includes contributions from gauge mediation in addition to the contributions from gravity mediation and anomaly mediation also present in mirage mediation. The threshold effects from gauge mediation can drastically alter the low energy spectrum from that of pure mirage mediation models, resulting in some cases in a squeezed gaugino spectrum and a gluino that is much lighter than other colored superpartners. We provide several benchmark deflected mirage mediation models and construct model lines as a function of the gauge mediation contributions, and discuss their discovery potential at the LHC.Comment: 29 pages, 9 figure

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

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