We report the detection of absorption lines by the reactive ions OH+, H2O+and H3O+ along the line of sight to the submillimeter continuum source G10.6-0.4 (W31C). We used the Herschel HIFI instrument ...in dual beam switch mode to observe the ground state rotational transitions of OH+ at 971 GHz, H2O+ at 1115 and 607 GHz, and H3O+ at 984 GHz. The resultant spectra show deep absorption over a broad velocity range that originates in the interstellar matter along the line of sight to G10.6-0.4 as well as in the molecular gas directly associated with that source. The OH+ spectrum reaches saturation over most velocities corresponding to the foreground gas, while the opacity of the H2O+ lines remains lower than 1 in the same velocity range, and the H3O+line shows only weak absorption. For LSR velocities between 7 and 50 km s-1 we estimate total column densities of N(OH+) >= 2.5 × 1014 cm-2, N(H2O+) ~6 × 1013 cm-2 and N(H3O+) ~4.0 × 1013 cm-2. These detections confirm the role of O+ and OH+ in initiating the oxygen chemistry in diffuse molecular gas and strengthen our understanding of the gas phase production of water. The high ratio of the OH+ by the H2O+ column density implies that these species predominantly trace low-density gas with a small fraction of hydrogen in molecular form.
Obtaining reliable distance estimates to gas clouds within the Milky Way is challenging in the absence of certain tracers. The kinematic distance approach has been used as an alternative, derived ...from the assumption of circular trajectories around the Galactic centre. Consequently, significant errors are expected in regions where gas flow deviates from purely circular motions. We aim to quantify the systematic errors that arise from the kinematic distance method in the presence of a Galactic potential that is non-axisymmetric. We investigate how these errors differ in certain regions of the Galaxy and how they relate to the underlying dynamics. We perform 2D isothermal hydrodynamical simulation of the gas disk with the moving-mesh code Arepo, adding the capability of using an external potential provided by the Agama library for galactic dynamics. We introduce a new analytic potential of the Milky Way, taking elements from existing models and adjusting parameters to match recent observational constraints. We find significant errors in the kinematic distance estimate for gas close to the Sun, along sight lines towards the Galactic centre and anti-centre, and significant deviations associated with the Galactic bar. Kinematic distance errors are low within the spiral arms as gas resides close to local potential minima and the resulting line-of-sight velocity is close to what is expected for an axisymmetric potential. Interarm regions exhibit large deviations at any given Galactic radius. This is caused by the gas being sped up or slowed down as it travels into or out of the spiral arm. We are able to define 'zones of avoidance' in the lv-diagram, where the kinematic distance method is particularly unreliable and should only be used with caution. We report a power law relation between the kinematic distance error and the deviation of the project line-of-sight velocity from circular motion.
Irinotecan (CPT-11) is a topoisomerase I inhibitor commonly used in the treatment of colorectal tumors. It is a prodrug, converted to an active metabolite, SN-38, by carboxylesterases (CEs). CEs are ...ubiquitary enzymes that react with numerous substrates. A specific CPT-11 converting enzyme was isolated from rat serum, with different kinetic properties than other CEs. We determined kinetic properties of specific CPT-11 CE activity (CPT-CE) in human normal liver and colon tumors. Km were very similar (3.4 μM in liver and 3.8 μM in colon tumors), but Vmax was higher in liver (2.7 pmol/min/mg protein) than in colon tumor (1.7 pmol/min/mg protein). CPT-CE and total CE (using p-nitro-phenylacetate as substrate) were weakly correlated in colon tumors. The large interpatient variability observed in liver CPT-CE activity could play a potential role in the pharmacokinetic variability observed with irinotecan.
Paclitaxel and vinorelbine are two drugs active against breast cancer. A phase II study was initiated with the aim of assessing the efficacy and feasibility of the combination. Twenty-six patients ...presenting with advanced breast cancer with a taxane- and vinorelbine-free line of chemotherapy were included and treated with vinorelbine (20 mg/m2 on D1, D15), followed by paclitaxel (175 mg/m2 on D1), every 3 weeks. A 48% (95% CI: 35-61) response rate was obtained in the 23 patients evaluable for response. Vinorelbine was administered on D15, as scheduled, in 72% of cycles. The main toxicity observed was grade III to IV neutropenia in 73% of patients. Febrile neutropenia was reported in three patients. Disease-free survival was 118 days, and overall median survival was 361 days. This combination of paclitaxel and vinorelbine is feasible and effective in patients with early relapse or previously treated with first-line chemotherapy for metastatic disease.
CPT-11 is a prodrug activated by carboxylesterases to the active metabolite SN-38 which is a potent inhibitor of topoisomerase I. CPT-11 is of clinical interest in the treatment of colorectal cancer. ...We evaluated the activities of CPT-11 converting carboxylesterase (CPT-CE) and topoisomerase I (topo I) in 53 colorectal tumours, in eight liver metastases and in normal tissue adjacent to the tumours. Both CPT-CE and topo I activities were widely variable in the malignant and the normal tissue of patients with colorectal carcinomas. CPT-CE was only two to threefold lower in primary tumours compared to normal liver, suggesting that a local conversion to SN-38 might occur in tumour cells. CPT-CE was similar in liver and in normal colon tissues. Levels of topo I in tumour ranged from 580 to 84 900 U mg protein(-1) and was above 40 000 U mg protein(-1) in 11 of 53 patients. Similarly, a very high ratio (> 5) between tumour and normal tissues were observed in 12 of 53 patients. An inverse correlation was observed between the topo I activity and the clinical stage of disease. Clinical studies are in progress in our institution to explore a possible relationship between CPT-CE and topo I activities in tumour cells and the response to CPT-11-based chemotherapy in patients with colorectal cancer.
We review current theories for the origin of the Stellar Initial Mass Function (IMF) with particular focus on the extent to which the IMF can be considered universal across various environments. To ...place the issue in an observational context, we summarize the techniques used to determine the IMF for different stellar populations, the uncertainties affecting the results, and the evidence for systematic departures from universality under extreme circumstances. We next consider theories for the formation of prestellar cores by turbulent fragmentation and the possible impact of various thermal, hydrodynamic and magneto-hydrodynamic instabilities. We address the conversion of prestellar cores into stars and evaluate the roles played by different processes: competitive accretion, dynamical fragmentation, ejection and starvation, filament fragmentation and filamentary accretion flows, disk formation and fragmentation, critical scales imposed by thermodynamics, and magnetic braking. We present explanations for the characteristic shapes of the Present-Day Prestellar Core Mass Function and the IMF and consider what significance can be attached to their apparent similarity. Substantial computational advances have occurred in recent years, and we review the numerical simulations that have been performed to predict the IMF directly and discuss the influence of dynamics, time-dependent phenomena, and initial conditions.
In order to study the fragmentation of massive dense cores, which constitute the cluster cradles, we observed with the PdBI in the most extended configuration the continuum at 1.3 mm and the CO(2-1) ...emission of four massive cores. We detect dust condensations down to ~0.3 Msun and separate millimeter sources down to 0.4" or ~1000 AU, comparable to the sensitivities and separations reached in optical/infrared studies of clusters. The CO(2-1) high angular resolution images reveal high-velocity knots usually aligned with previously known outflow directions. This, in combination with additional cores from the literature observed at similar mass sensitivity and spatial resolution, allowed us to build a sample of 18 protoclusters with luminosities spanning 3 orders of magnitude. Among the 18 regions, ~30% show no signs of fragmentation, while 50% split up into ~4 millimeter sources. We compiled a list of properties for the 18 massive dense cores, such as bolometric luminosity, total mass, and mean density, and found no correlation of any of these parameters with the fragmentation level. In order to investigate the combined effects of magnetic field, radiative feedback and turbulence in the fragmentation process, we compared our observations to radiation magneto-hydrodynamic simulations, and found that the low-fragmented regions are well reproduced in the magnetized core case, while the highly-fragmented regions are consistent with cores where turbulence dominates over the magnetic field. Overall, our study suggests that the fragmentation in massive dense cores could be determined by the initial magnetic field/turbulence balance in each particular core.
The identification of factors associated with breast recurrence as first event (62 cases, 10%) following conservative surgery and radiation therapy are drawn out from a series++ of 618 mammary ...carcinomas of clinical size less than 40 mm, stage I and II (UICC), with a median follow up of 8 years. The most powerful predictive characteristic associated with the likelihood of breast recurrence is multiple foci of invasion (42.9% vs 8.9, P = 0.0001, relative risk RR: 6). After this rarely cited feature, young age, less than 40 years (20% vs 7.3%, P = 0.0001, RR: 2.8), extensive in situ carcinoma more than 25% (19.2% vs 8.7%, P = 0.003, RR: 2.5) were found also persistent in the Cox model, but not histologic size more than 25 mm (18.9% vs 9.1%, P = 0.01, RR: 2.3). The site of recurrence was studied on the 54 salvage mastectomy done. A high rate of recurrence at distance of the initial site was found: 37% whose more than half, 22%, were multicentric. No significant difference in the mean delay of appearance was noted between recurrence near or at distance of the initial cancer (mean delay 52 months vs 64 months). From the recurrence the evolution is not very favourable: excluding simultaneous metastases found at the preoperative investigation, ten cases, mammary recurrence is followed by a metastatic syndrome in 36% of cases against 17% without it (P = 0.01, RR: 1.9). Metastatic evolution is not significantly linked with the time, early or late, of the mammary recurrence (54.5% before 5 years vs 39% after) but with the association of a controlateral cancer (P = 0.03). Locally ten of the 54 mastectomy presented a thoracic recurrence, often in case of multicentric breast recurrence (P = 0.05) and not significantly when skin or areola were invaded by carcinoma.
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