Dwarf satellite galaxies in the modified dynamics

In the modified dynamics (MOND) the inner workings of dwarf satellites can be greatly affected by their mother galaxy-over and beyond its tidal effects. Because of MOND's nonlinearity a system's internal dynamics can be altered by an external field in which it is immersed (even when this field, by itself, is constant in space). As a result, the size and velocity dispersion of the satellite vary as the external field varies along its orbit. A notable outcome of this is a substantial increase in the dwarf's vulnerability to eventual tidal disruption-rather higher than Newtonian dynamics (with a dark-matter halo) would lead us to expect for a satellite with given observed parameters.Comment: 15 pages with 5 embedded figures; Astrophysical J in press Corrected error in names of author

A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse.

A randomized, multicentre, open-label, phase II study compared temozolomide (TMZ), an oral second-generation alkylating agent, and procarbazine (PCB) in 225 patients with glioblastoma multiforme at first relapse. Primary objectives were to determine progression-free survival (PFS) at 6 months and safety for TMZ and PCB in adult patients who failed conventional treatment. Secondary objectives were to assess overall survival and health-related quality of life (HRQL). TMZ was given orally at 200 mg/m(2)/day or 150 mg/m(2)/day (prior chemotherapy) for 5 days, repeated every 28 days. PCB was given orally at 150 mg/m(2)/day or 125 mg/m(2)/day (prior chemotherapy) for 28 days, repeated every 56 days. HRQL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 [+3]) and the Brain Cancer Module 20 (BCM20). The 6-month PFS rate for patients who received TMZ was 21%, which met the protocol objective. The 6-month PFS rate for those who received PCB was 8% (P = 0.008, for the comparison). Overall PFS significantly improved with TMZ, with a median PFS of 12.4 weeks in the TMZ group and 8.32 weeks in the PCB group (P = 0.0063). The 6-month overall survival rate for TMZ patients was 60% vs. 44% for PCB patients (P = 0.019). Freedom from disease progression was associated with maintenance of HRQL, regardless of treatment received. TMZ had an acceptable safety profile; most adverse events were mild or moderate in severity

On the gravitational potential of modified Newtonian dynamics

Producción CientíficaThe mathematical structure of the Poisson equation of Modified Newtonian Dynamics (MOND) is studied. The appropriate setting turns out to be an Orlicz-Sobolev space whose Orlicz function is related to Milgrom’s μ-function, where there exists existence and uniqueness of weak solutions. Since these do not have in principle much regularity, a further study is performed where the gravitational field is not too large, where MOND is most relevant. In that case the field turns out to be H¨older continuous. Quasilinear MOND is also analyzed

Galactic kinematics with modified Newtonian dynamics

We look for observational signatures that could discriminate between Newtonian and modified Newtonian (MOND) dynamics in the Milky Way, in view of the advent of large astrometric and spectroscopic surveys. Indeed, a typical signature of MOND is an apparent disk of "phantom" dark matter, which is uniquely correlated with the visible disk-density distribution. Due to this phantom dark disk, Newtonian models with a spherical halo have different signatures from MOND models close to the Galactic plane. The models can thus be differentiated by measuring dynamically (within Newtonian dynamics) the disk surface density at the solar radius, the radial mass gradient within the disk, or the velocity ellipsoid tilt angle above the Galactic plane. Using the most realistic possible baryonic mass model for the Milky Way, we predict that, if MOND applies, the local surface density measured by a Newtonist will be approximately 78 Msun/pc2 within 1.1 kpc of the Galactic plane, the dynamically measured disk scale-length will be enhanced by a factor of 1.25 with respect to the visible disk scale-length, and the local vertical tilt of the velocity ellipsoid at 1 kpc above the plane will be approximately 6 degrees. None of these tests can be conclusive for the present-day accuracy of Milky Way data, but they will be of prime interest with the advent of large surveys such as GAIA.Comment: 5 page

Dynamic scaling for 2D superconductors, Josephson junction arrays and superfluids

The value of the dynamic critical exponent $z$ is studied for two-dimensional superconducting, superfluid, and Josephson Junction array systems in zero magnetic field via the Fisher-Fisher-Huse dynamic scaling. We find $z\simeq5.6\pm0.3$, a relatively large value indicative of non-diffusive dynamics. Universality of the scaling function is tested and confirmed for the thinnest samples. We discuss the validity of the dynamic scaling analysis as well as the previous studies of the Kosterlitz-Thouless-Berezinskii transition in these systems, the results of which seem to be consistent with simple diffusion ($z=2$). Further studies are discussed and encouraged.Comment: 19 pages in two-column RevTex, 8 embedded EPS figure

Glioblastoma adaptation traced through decline of an IDH1 clonal driver and macro-evolution of a double-minute chromosome

Background: Glioblastoma (GBM) is the most common malignant brain cancer occurring in adults, and is associated with dismal outcome and few therapeutic options. GBM has been shown to predominantly disrupt three core pathways through somatic aberrations, rendering it ideal for precision medicine approaches. Methods: We describe a 35-year-old female patient with recurrent GBM following surgical removal of the primary tumour, adjuvant treatment with temozolomide and a 3-year disease-free period. Rapid whole-genome sequencing (WGS) of three separate tumour regions at recurrence was carried out and interpreted relative to WGS of two regions of the primary tumour. Results: We found extensive mutational and copy-number heterogeneity within the primary tumour. We identified a TP53 mutation and two focal amplifications involving PDGFRA, KIT and CDK4, on chromosomes 4 and 12. A clonal IDH1 R132H mutation in the primary, a known GBM driver event, was detectable at only very low frequency in the recurrent tumour. After sub-clonal diversification, evidence was found for a whole-genome doubling event and a translocation between the amplified regions of PDGFRA, KIT and CDK4, encoded within a double-minute chromosome also incorporating miR26a-2. The WGS analysis uncovered progressive evolution of the double-minute chromosome converging on the KIT/PDGFRA/PI3K/mTOR axis, superseding the IDH1 mutation in dominance in a mutually exclusive manner at recurrence, consequently the patient was treated with imatinib. Despite rapid sequencing and cancer genome-guided therapy against amplified oncogenes, the disease progressed, and the patient died shortly after. Conclusion: This case sheds light on the dynamic evolution of a GBM tumour, defining the origins of the lethal sub-clone, the macro-evolutionary genomic events dominating the disease at recurrence and the loss of a clonal driver. Even in the era of rapid WGS analysis, cases such as this illustrate the significant hurdles for precision medicine success

Glioblastoma adaptation traced through decline of an IDH1 clonal driver and macro-evolution of a double-minute chromosome

In a glioblastoma tumour with multi-region sequencing before and after recurrence, we find an IDH1 mutation that is clonal in the primary but lost at recurrence. We also describe the evolution of a double-minute chromosome encoding regulators of the PI3K signalling axis that dominates at recurrence, emphasizing the challenges of an evolving and dynamic oncogenic landscape for precision medicin

Observational Constraints on the Modified Gravity Model (MOG) Proposed by Moffat: Using the Magellanic System

A simple model for the dynamics of the Magellanic Stream (MS), in the framework of modified gravity models is investigated. We assume that the galaxy is made up of baryonic matter out of context of dark matter scenario. The model we used here is named Modified Gravity (MOG) proposed by Moffat (2005). In order to examine the compatibility of the overall properties of the MS under the MOG theory, the observational radial velocity profile of the MS is compared with the numerical results using the $\chi^2$ fit method. In order to obtain the best model parameters, a maximum likelihood analysis is performed. We also compare the results of this model with the Cold Dark Matter (CDM) halo model and the other alternative gravity model that proposed by Bekenstein (2004), so called TeVeS. We show that by selecting the appropriate values for the free parameters, the MOG theory seems to be plausible to explain the dynamics of the MS as well as the CDM and the TeVeS models.Comment: 14 pages, 3 Figures, accepted in Int. J. Theor. Phy

Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse

Background: Recurrent glioblastoma multiforme (GBM) is resistant to most therapeutic endeavors, with low response rates and survival rarely exceeding six months. There are no clearly established chemotherapeutic regimens and the aim of treatment is palliation with improvement in the quality of life. Patients and methods: We report an open-label, uncontrolled, multicenter phase II trial of temozolomide in 138 patients (intent-to-treat [ITI] population) with glioblastoma multiforme at first relapse and a Karnofsky performance status (KPS) ≥ 70. One hundred twenty-eight patients were histologically confirmed with GBM or gliosarcoma (GS) by independent central review. Chemotherapy-naïve patients were treated with temozolomide 200 mg/m2/day2/day orally for the first five days of a 28-day cycle. Patients previously treated with nitrosourea- containing adjuvant chemotherapy received 150 mg/m2/day for the first five days of a 28-day cycle. In the absence of grade 3 or 4 toxicity, patients on the 150 mg/m2 dose schedule were eligible for a 200 mg/m2 dose on the next cycle. Results: The primary endpoint was six-month progression-free survival assessed with strict radiological and clinical criteria. Secondary endpoints included radiological response and Health-related Quality of Life (HQL). Progression-free survival at six months was 18% (95% confidence interval (CI): 11%-26%) for the eligible-histology population. Median progression-free survival and median overall survival were 2.1 months and 5.4 months, respectively. The six-month survival rate was 46%. The objective response rate (complete response and partial response) determined by independent central review of gadolinium-enhanced magnetic resonance imaging (MRI) scans was 8% for both the ITT and eligible-histology populations, with an additional 43%;A and 45% of patients, respectively, having stable disease (SD). Objectively assessed response and maintenance of a progression-free status were both associated with HQL benefits (characterized by improvements over baseline in HQL domains). Temozolomide had an acceptable safety profile, with only 9% of therapy cycles requiring a dose reduction due to thrombocytopenia. There was no evidence of cumulative hematologic toxicity. Conclusions: Temozolomide demonstrated modest clinical efficacy, with an acceptable safety profile and measurable improvement in quality of life in patients with recurrent GBM. The use of this drug should be explored further in an adjuvant setting and in combination with other agent

Local-Group tests of dark-matter Concordance Cosmology: Towards a new paradigm for structure formation

(abridged) Predictions of the Concordance Cosmological Model (CCM) of the structures in the environment of large spiral galaxies are compared with observed properties of Local Group galaxies. Five new most probably irreconcilable problems are uncovered. However, the Local Group properties provide hints that may lead to a solution of the above problems The DoS and bulge--satellite correlation suggest that dissipational events forming bulges are related to the processes forming phase-space correlated satellite populations. Such events are well known to occur since in galaxy encounters energy and angular momentum are expelled in the form of tidal tails, which can fragment to form populations of tidal-dwarf galaxies (TDGs) and associated star clusters. If Local Group satellite galaxies are to be interpreted as TDGs then the sub-structure predictions of CCM are internally in conflict. All findings thus suggest that the CCM does not account for the Local Group observations and that therefore existing as well as new viable alternatives have to be further explored. These are discussed and natural solutions for the above problems emerge.Comment: A and A, in press, 25 pages, 9 figures; new version contains minor text adjustments for conformity with the published version and additional minor changes resulting from reader's feedback. The speculation on a dark force has been added. Also, the Fritz Zwicky Paradox is now included to agree with the published versio