Discovery of molecular subtypes in leiomyosarcoma through integrative molecular profiling.

Leiomyosarcoma (LMS) is a soft tissue tumor with a significant degree of morphologic and molecular heterogeneity. We used integrative molecular profiling to discover and characterize molecular subtypes of LMS. Gene expression profiling was performed on 51 LMS samples. Unsupervised clustering showed three reproducible LMS clusters. Array comparative genomic hybridization (aCGH) was performed on 20 LMS samples and showed that the molecular subtypes defined by gene expression showed distinct genomic changes. Tumors from the muscle-enriched cluster showed significantly increased copy number changes (P=0.04). A majority of the muscle-enriched cases showed loss at 16q24, which contains Fanconi anemia, complementation group A, known to have an important role in DNA repair, and loss at 1p36, which contains PRDM16, of which loss promotes muscle differentiation. Immunohistochemistry (IHC) was performed on LMS tissue microarrays (n=377) for five markers with high levels of messenger RNA in the muscle-enriched cluster (ACTG2, CASQ2, SLMAP, CFL2 and MYLK) and showed significantly correlated expression of the five proteins (all pairwise P<0.005). Expression of the five markers was associated with improved disease-specific survival in a multivariate Cox regression analysis (P<0.04). In this analysis that combined gene expression profiling, aCGH and IHC, we characterized distinct molecular LMS subtypes, provided insight into their pathogenesis, and identified prognostic biomarkers

Occultation analysis of BATSE data: Operational aspects

The Burst and Transient Source Experiment (BATSE) large area detectors are being used to monitor hard x-ray/gamma ray sources on a daily basis for evidence of transient behavior. Flux measurements are performed using a simple earth occultation technique. Daily searches are also being performed to detect occultation steps of sources which are not being routinely monitored. Topics concerning the operational aspects of the occultation measurements are presented. Preliminary spectral results are also presented for several of the brighter sources

Lohnsubventionen in Deutschland: wie sieht eine optimale Evaluierungsstrategie aus?

Lohnsubventionen werden als eine relativ flexible und effiziente Methode gesehen, um die Nachfrage nach gering qualifizierten Arbeitnehmern zu erhöhen und ihre Einkommens- und Beschäftigungschancen zu verbessern. Auch in Deutschland gewinnt die Förderung durch dieses Instrument aktiver Arbeitsmarktpolitik einerseits zunehmend an Bedeutung, wird andererseits aber auch kritisiert. Neben dem aus humankapitaltheoretischer Sicht fehlenden Weiterbildungsaspekt steht vor allem das Auftreten von Mitnahme-, Substitutions- und Verdrängungseffekten im Mittelpunkt der Kritik. Diese Effekte konterkarieren die erhoffte positive Wirkung von Lohnsubventionen und sind in der Regel schwer zu messen. Wir skizzieren in diesem Papier eine dreistufige Evaluierungsstrategie, bei der zunächst auf mikroökonomischer Ebene die Wirkung der Subvention auf den geförderten Arbeitnehmer untersucht wird. Anschließend steht die Arbeitsnachfrage im Vordergrund des Interesses, um Mitnahme- und Substitutionseffekte innerhalb eines Unternehmens zu ermitteln, bevor die Effekte auf gesamtwirtschaftlicher Ebene analysiert werden sollen. Die umfassende empirische Evaluation von Lohnsubventionen in Deutschland steht noch aus, da die dafür notwendigen Daten noch nicht zur Verfügung stehen. Sobald dies der Fall ist, kann eine Bewertung auf den drei angesprochenen Ebenen erfolgen

Global monopole, dark matter and scalar tensor theory

In this article, we discuss the space-time of a global monopole field as a candidate for galactic dark matter in the context of scalar tensor theory.Comment: 8 pages, Accepted in Mod. Phys. Lett.

A Sequence of Declining Outbursts from GX339-4

The flux and spectrum of the black hole candidate GX339-4 has been monitored by the Burst and Transient Source Experiment (BATSE) on the Compton Gamma-ray Observatory (CGRO) since the observatory became operational in May 1991. Between the summer of 1991 and the fall of 1996, eight outbursts from GX339-4 were observed. The history of these outbursts is one of declining fluence or total energy release, as well as a shortening of the time between outbursts. A rough linear correlation exists between the fluence emitted during an outburst and the time elapsed between the end of the previous outburst and the beginning of the current one. The peak flux is also roughly linearly correlated with outburst fluence. The lightcurves of the earlier, more intense, outbursts (except for the second one) can be modeled by a fast exponential (time constant ~ 10 days) followed by a slower exponential (~ 100 days) on the rise and a fast exponential decay (~ 5 days) on the fall. The later, weaker, outbursts are modeled with a single rising time constant (~ 20 days) and a longer decay on the fall (~ 50 days). An exponential model gives a marginally better fit than a power law to the rise/decay profiles. GX339-4 is a unique source in having more frequent outbursts than other low mass x-ray binary black hole candidates. These observations can be used to constrain models of the behavior of the accretion disk surrounding the compact object.Comment: Accepted for Publication in the Astrophysical Journal Letters, AASTE

Resistance-promoting effects of ependymoma treatment revealed through genomic analysis of multiple recurrences in a single patient

As in other brain tumors, multiple recurrences after complete resection and irradiation of supratentorial ependymoma are common and frequently result in patient death. This standard-of-care treatment was established in the pregenomic era without the ability to evaluate the effect that mutagenic therapies may exert on tumor evolution and in promoting resistance, recurrence, and death. We seized a rare opportunity to characterize treatment effects and the evolution of a single patient's ependymoma across four recurrences after different therapies. A combination of high-depth whole-genome and exome-based DNA sequencing of germline and tumor specimens, RNA sequencing of tumor specimens, and advanced computational analyses were used. Treatment with radiation and chemotherapies resulted in a substantial increase in mutational burden and diversification of the tumor subclonal architecture without eradication of the founding clone. Notable somatic alterations included a MEN1 driver, several epigenetic modifiers, and therapy-induced mutations that impacted multiple other cancer-relevant pathways and altered the neoantigen landscape. These genomic data provided new mechanistic insights into the genesis of ependymoma and pathways of resistance. They also revealed that radiation and chemotherapy were significant forces in shaping the increased subclonal complexity of each tumor recurrence while also failing to eradicate the founding clone. This raises the question of whether standard-of-care treatments have similar consequences in other patients with ependymoma and other types of brain tumors. If so, the perspective obtained by real-time genomic characterization of a tumor may be essential for making effective patient-specific and adaptive clinical decisions.</jats:p

Fermionic and Bosonic Stabilizing Effects for Type I and Type II Dimension Bubbles

We consider two types of "dimension bubbles", which are viewed as 4d nontopological solitons that emerge from a 5d theory with a compact extra dimension. The size of the extra dimension varies rapidly within the domain wall of the soliton. We consider the cases of type I (II) bubbles where the size of the extra dimension inside the bubble is much larger (smaller) than outside. Type I bubbles with thin domain walls can be stabilized by the entrapment of various particle modes whose masses become much smaller inside than outside the bubble. This is demonstrated here for the cases of scalar bosons, fermions, and massive vector bosons, including both Kaluza-Klein zero modes and Kaluza-Klein excitation modes. Type II bubbles expel massive particle modes but both types can be stabilized by photons. Plasma filled bubbles containing a variety of massless or nearly massless radiation modes may exist as long-lived metastable states. Furthermore, in contrast to the case with a "gravitational bag", the metric for a fluid-filled dimension bubble does not exhibit a naked singularity at the bubble's center.Comment: 17 pages, no figs; to appear in Phys.Rev.

Jet substructure as a new Higgs search channel at the LHC

It is widely considered that, for Higgs boson searches at the Large Hadron Collider, WH and ZH production where the Higgs boson decays to b anti-b are poor search channels due to large backgrounds. We show that at high transverse momenta, employing state-of-the-art jet reconstruction and decomposition techniques, these processes can be recovered as promising search channels for the standard model Higgs boson around 120 GeV in mass.Comment: 4 pages, 3 figure

Zeta-Functions for Non-Minimal Operators

We evaluate zeta-functions $\zeta(s)$ at $s=0$ for invariant non-minimal 2nd-order vector and tensor operators defined on maximally symmetric even dimensional spaces. We decompose the operators into their irreducible parts and obtain their corresponding eigenvalues. Using these eigenvalues, we are able to explicitly calculate $\zeta(0)$ for the cases of Euclidean spaces and $N$-spheres. In the $N$-sphere case, we make use of the Euler-Maclaurin formula to develop asymptotic expansions for the required sums. The resulting $\zeta(0)$ values for dimensions 2 to 10 are given in the Appendix.Comment: 26 pages, additional reference