The impact of chromosomal translocation locus and fusion oncogene coding sequence in synovial sarcomagenesis.

Synovial sarcomas are aggressive soft-tissue malignancies that express chromosomal translocation-generated fusion genes, SS18-SSX1 or SS18-SSX2 in most cases. Here, we report a mouse sarcoma model expressing SS18-SSX1, complementing our prior model expressing SS18-SSX2. Exome sequencing identified no recurrent secondary mutations in tumors of either genotype. Most of the few mutations identified in single tumors were present in genes that were minimally or not expressed in any of the tumors. Chromosome 6, either entirely or around the fusion gene expression locus, demonstrated a copy number gain in a majority of tumors of both genotypes. Thus, by fusion oncogene coding sequence alone, SS18-SSX1 and SS18-SSX2 can each drive comparable synovial sarcomagenesis, independent from other genetic drivers. SS18-SSX1 and SS18-SSX2 tumor transcriptomes demonstrated very few consistent differences overall. In direct tumorigenesis comparisons, SS18-SSX2 was slightly more sarcomagenic than SS18-SSX1, but equivalent in its generation of biphasic histologic features. Meta-analysis of human synovial sarcoma patient series identified two tumor-gentoype-phenotype correlations that were not modeled by the mice, namely a scarcity of male hosts and biphasic histologic features among SS18-SSX2 tumors. Re-analysis of human SS18-SSX1 and SS18-SSX2 tumor transcriptomes demonstrated very few consistent differences, but highlighted increased native SSX2 expression in SS18-SSX1 tumors. This suggests that the translocated locus may drive genotype-phenotype differences more than the coding sequence of the fusion gene created. Two possible roles for native SSX2 in synovial sarcomagenesis are explored. Thus, even specific partial failures of mouse genetic modeling can be instructive to human tumor biology

Top Quarks as a Window to String Resonances

We study the discovery potential of string resonances decaying to $t\bar{t}$ final state at the LHC. We point out that top quark pair production is a promising and an advantageous channel for studying such resonances, due to their low Standard Model background and unique kinematics. We study the invariant mass distribution and angular dependence of the top pair production cross section via exchanges of string resonances. The mass ratios of these resonances and the unusual angular distribution may help identify their fundamental properties and distinguish them from other new physics. We find that string resonances for a string scale below 4 TeV can be detected via the $t\bar{t}$ channel, either from reconstructing the $t\bar{t}$ semi-leptonic decay or recent techniques in identifying highly boosted tops.Comment: 22 pages, 6 figure

Evidence for F(uzz) Theory

We show that in the decoupling limit of an F-theory compactification, the internal directions of the seven-branes must wrap a non-commutative four-cycle S. We introduce a general method for obtaining fuzzy geometric spaces via toric geometry, and develop tools for engineering four-dimensional GUT models from this non-commutative setup. We obtain the chiral matter content and Yukawa couplings, and show that the theory has a finite Kaluza-Klein spectrum. The value of 1/alpha_(GUT) is predicted to be equal to the number of fuzzy points on the internal four-cycle S. This relation puts a non-trivial restriction on the space of gauge theories that can arise as a limit of F-theory. By viewing the seven-brane as tiled by D3-branes sitting at the N fuzzy points of the geometry, we argue that this theory admits a holographic dual description in the large N limit. We also entertain the possibility of constructing string models with large fuzzy extra dimensions, but with a high scale for quantum gravity.Comment: v2: 66 pages, 3 figures, references and clarifications adde

Superpotential de-sequestering in string models

Non-perturbative superpotential cross-couplings between visible sector matter and K\"ahler moduli can lead to significant flavour-changing neutral currents in compactifications of type IIB string theory. Here, we compute corrections to Yukawa couplings in orbifold models with chiral matter localised on D3-branes and non-perturbative effects on distant D7-branes. By evaluating a threshold correction to the D7-brane gauge coupling, we determine conditions under which the non-perturbative corrections to the Yukawa couplings appear. The flavour structure of the induced Yukawa coupling generically fails to be aligned with the tree-flavour structure. We check our results by also evaluating a correlation function of two D7-brane gauginos and a D3-brane Yukawa coupling. Finally, by calculating a string amplitude between n hidden scalars and visible matter we show how non-vanishing vacuum expectation values of distant D7-brane scalars, if present, may correct visible Yukawa couplings with a flavour structure that differs from the tree-level flavour structure.Comment: 37 pages + appendices, 8 figure

Single-Scale Natural SUSY

We consider the prospects for natural SUSY models consistent with current data. Recent constraints make the standard paradigm unnatural so we consider what could be a minimal extension consistent with what we now know. The most promising such scenarios extend the MSSM with new tree-level Higgs interactions that can lift its mass to at least 125 GeV and also allow for flavor-dependent soft terms so that the third generation squarks are lighter than current bounds on the first and second generation squarks. We argue that a common feature of almost all such models is the need for a new scale near 10 TeV, such as a scale of Higgsing or confinement of a new gauge group. We consider the question whether such a model can naturally derive from a single mass scale associated with supersymmetry breaking. Most such models simply postulate new scales, leaving their proximity to the scale of MSSM soft terms a mystery. This coincidence problem may be thought of as a mild tuning, analogous to the usual mu problem. We find that a single mass scale origin is challenging, but suggest that a more natural origin for such a new dynamical scale is the gravitino mass, m_{3/2}, in theories where the MSSM soft terms are a loop factor below m_{3/2}. As an example, we build a variant of the NMSSM where the singlet S is composite, and the strong dynamics leading to compositeness is triggered by masses of order m_{3/2} for some fields. Our focus is the Higgs sector, but our model is compatible with a light stop (with the other generation squarks heavy, or with R-parity violation or another mechanism to hide them from current searches). All the interesting low-energy mass scales, including linear terms for S playing a key role in EWSB, arise dynamically from the single scale m_{3/2}. However, numerical coefficients from RG effects and wavefunction factors in an extra dimension complicate the otherwise simple story.Comment: 32 pages, 3 figures; version accepted by JHE

On domain walls in a Ginzburg-Landau non-linear S^2-sigma model

The domain wall solutions of a Ginzburg-Landau non-linear $S^2$-sigma hybrid model are unveiled. There are three types of basic topological walls and two types of degenerate families of composite - one topological, the other non-topological- walls. The domain wall solutions are identified as the finite action trajectories (in infinite time) of a related mechanical system that is Hamilton-Jacobi separable in sphero-conical coordinates. The physical and mathematical features of these domain walls are thoroughly discussed.Comment: 26 pages, 18 figure

Smooth tensionful higher-codimensional brane worlds with bulk and brane form fields

Completely regular tensionful codimension-n brane world solutions are discussed, where the core of the brane is chosen to be a thin codimension-(n-1) shell in an infinite volume flat bulk, and an Einstein-Hilbert term localized on the brane is included (Dvali-Gabadadze-Porrati models). In order to support such localized sources we enrich the vacuum structure of the brane by the inclusion of localized form fields. We find that phenomenological constraints on the size of the internal core seem to impose an upper bound to the brane tension. Finite transverse-volume smooth solutions are also discussed.Comment: 1+14 pages, 2 figures; section 2.3 improved, typos corrected and references added. Published versio

Evaluating privacy-preserving record linkage using cryptographic long-term keys and multibit trees on large medical datasets.

Background: Integrating medical data using databases from different sources by record linkage is a powerful technique increasingly used in medical research. Under many jurisdictions, unique personal identifiers needed for linking the records are unavailable. Since sensitive attributes, such as names, have to be used instead, privacy regulations usually demand encrypting these identifiers. The corresponding set of techniques for privacy-preserving record linkage (PPRL) has received widespread attention. One recent method is based on Bloom filters. Due to superior resilience against cryptographic attacks, composite Bloom filters (cryptographic long-term keys, CLKs) are considered best practice for privacy in PPRL. Real-world performance of these techniques using large-scale data is unknown up to now. Methods: Using a large subset of Australian hospital admission data, we tested the performance of an innovative PPRL technique (CLKs using multibit trees) against a gold-standard derived from clear-text probabilistic record linkage. Linkage time and linkage quality (recall, precision and F-measure) were evaluated. Results: Clear text probabilistic linkage resulted in marginally higher precision and recall than CLKs. PPRL required more computing time but 5 million records could still be de-duplicated within one day. However, the PPRL approach required fine tuning of parameters. Conclusions: We argue that increased privacy of PPRL comes with the price of small losses in precision and recall and a large increase in computational burden and setup time. These costs seem to be acceptable in most applied settings, but they have to be considered in the decision to apply PPRL. Further research on the optimal automatic choice of parameters is needed

Enhanced Eyelashes: Prescription and Over-the-Counter Options

Women have long strived to possess long, thick, and dark eyelashes. Prominent eyes and eyelashes are often considered a sign of beauty and can be associated with increased levels of attractiveness, confidence, and well-being. Numerous options may improve the appearance of eyelashes. Mascara aims to temporarily darken, lengthen, and thicken eyelashes using a combination of waxes, pigments, and resins. Artificial eyelashes can be adhered either to the dermal margin or to individual eyelashes. Individuals may even use eyelash transplantations to improve the appearance of their eyelashes. The unique properties of eyelashes (e.g., relatively long telogen and short anagen phases compared with scalp hairs, slow rate of growth, and a lack of influence by androgens) may allow for specific aesthetic interventions to improve the appearance of natural eyelashes. Some over-the-counter (OTC) products may contain prostaglandin analogs that can affect eyelash growth, but neither the safety nor efficacy of these OTC cosmetics has been fully studied. Originally indicated for the reduction of intraocular pressure, the synthetic prostaglandin analog bimatoprost was recently approved for the treatment of hypotrichosis of the eyelashes. In a double-blinded, randomized, vehicle-controlled trial, bimatoprost safely and effectively grew natural eyelashes, making them longer, thicker, and darker. Bimatoprost was generally safe and well tolerated and appears to provide an additional option for individuals looking to improve the appearance of their eyelashes

Operating theatre related syncope in medical students: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>Observing surgical procedures is a beneficial educational experience for medical students during their surgical placements. Anecdotal evidence suggests that operating theatre related syncope may have detrimental effects on students' views of this. Our study examines the frequency and causes of such syncope, together with effects on career intentions, and practical steps to avoid its occurrence.</p> <p>Methods</p> <p>All penultimate and final year students at a large UK medical school were surveyed using the University IT system supplemented by personal approach. A 20-item anonymous questionnaire was distributed and results were analysed using the Statistical Package for Social Sciences, version 15.0 (Chicago, Illinois, USA).</p> <p>Results</p> <p>Of the 630 clinical students surveyed, 77 responded with details of at least one near or actual operating theatre syncope (12%). A statistically significant gender difference existed for syncopal/near-syncopal episodes (male 12%; female 88%), p < 0.05. Twenty-two percent of those affected were graduate entry medical course students with the remaining 78% undergraduate. Mean age was 23-years (range 20 – 45). Of the 77 reactors, 44 (57%) reported an intention to pursue a surgical career. Of this group, 7 (9%) reported being discouraged by syncopal episodes in the operating theatre. The most prevalent contributory factors were reported as hot temperature (n = 61, 79%), prolonged standing (n = 56, 73%), wearing a surgical mask (n = 36, 47%) and the smell of diathermy (n = 18, 23%). The most frequently reported measures that students found helpful in reducing the occurrence of syncopal episodes were eating and drinking prior to attending theatre (n = 47, 61%), and moving their legs whilst standing (n = 14, 18%).</p> <p>Conclusion</p> <p>Our study shows that operating theatre related syncope among medical students is common, and we establish useful risk factors and practical steps that have been used to prevent its occurrence. Our study also highlights the detrimental effect of this on the career intentions of medical students interested in surgery. Based on these findings, we recommend that dedicated time should be set aside in surgical teaching to address this issue prior to students attending the operating theatre.</p