Disentangling the circumnuclear environs of Centaurus A: II. On the nature of the broad absorption line

We report on atomic gas (HI) and molecular gas (as traced by CO(2-1)) redshifted absorption features toward the nuclear regions of the closest powerful radio galaxy, Centaurus A (NGC 5128). Our HI observations using the Very Long Baseline Array allow us to discern with unprecedented sub-parsec resolution HI absorption profiles toward different positions along the 21 cm continuum jet emission in the inner 0."3 (or 5.4 pc). In addition, our CO(2-1) data obtained with the Submillimeter Array probe the bulk of the absorbing molecular gas with little contamination by emission, not possible with previous CO single-dish observations. We shed light with these data on the physical properties of the gas in the line of sight, emphasizing the still open debate about the nature of the gas that produces the broad absorption line (~55 km/s). First, the broad H I line is more prominent toward the central and brightest 21 cm continuum component than toward a region along the jet at a distance ~ 20 mas (or 0.4 pc) further from it. This suggests that the broad absorption line arises from gas located close to the nucleus, rather than from diffuse and more distant gas. Second, the different velocity components detected in the CO(2-1) absorption spectrum match well other molecular lines, such as those of HCO+(1-0), except the broad absorption line that is detected in HCO+(1-0) (and most likely related to that of the H I). Dissociation of molecular hydrogen due to the AGN seems to be efficient at distances <= 10 pc, which might contribute to the depth of the broad H I and molecular lines.Comment: 17 pages, 9 figures, accepted for publication in Ap

3D Growth of Cancer Cells Elicits Sensitivity to Kinase Inhibitors but Not Lipid Metabolism Modifiers

Tumor cells exhibit altered lipid metabolism compared with normal cells. Cell signaling kinases are important for regulating lipid synthesis and energy storage. How upstream kinases regulate lipid content, versus direct targeting of lipid-metabolizing enzymes, is currently unexplored. We evaluated intracellular lipid concentrations in prostate and breast tumor spheroids, treated with drugs directly inhibiting metabolic enzymes fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC), diacylglyceride acyltransferase (DGAT), and pyruvate dehydrogenase kinase (PDHK), or cell signaling kinase enzymes PI3K, AKT, and mTOR with lipidomic analysis. We assessed whether baseline lipid profiles corresponded to inhibitors' effectiveness in modulating lipid profiles in three-dimensional (3D) growth and their relationship to therapeutic activity. Inhibitors against PI3K, AKT, and mTOR significantly inhibited MDA-MB-468 and PC3 cell growth in two-dimensional (2D) and 3D spheroid growth, while moderately altering lipid content. Conversely, metabolism inhibitors against FASN and DGAT altered lipid content most effectively, while only moderately inhibiting growth compared with kinase inhibitors. The FASN and ACC inhibitors' effectiveness in MDA-MB-468, versus PC3, suggested the former depended more on synthesis, whereas the latter may salvage lipids. Although baseline lipid profiles did not predict growth effects, lipid changes on therapy matched the growth effects of FASN and DGAT inhibitors. Several phospholipids, including phosphatidylcholine, were also upregulated following treatment, possibly via the Kennedy pathway. As this promotes tumor growth, combination studies should include drugs targeting it. Two-dimensional drug screening may miss important metabolism inhibitors or underestimate their potency. Clinical studies should consider serial measurements of tumor lipids to prove target modulation. Pretherapy tumor classification by de novo lipid synthesis versus uptake may help demonstrate efficacy

Tumor biopsy and patient enrollment in clinical trials for advanced hepatocellular carcinoma

Tumor biopsies may help to reliably distinguish hepatocellular carcinoma (HCC) from other tumors, mostly cholangiocarcinoma as well as to identify the patient populations who most benefit from target-driven HCC treatments, in order to improve the success rate of experimental therapies. Clarifying tumor biology may also lead to identify biomarkers with prognostic role and/or enabling to predict response or resistance to therapies. Recently, clinical trials have more efficiently included biomarker endpoints and increasingly collected tumor tissue from enrolled patients. Due to their frail status and sometimes fast-progressing disease, the performance status of patients with HCC progressing on first-line therapy can deteriorate quickly, preventing their enrollment in clinical trials. However, the challenge of identifying the proper patient at the proper time can be overcome by periodic inter-department meetings involving the key specialists taking care of HCC patients, and solid networks between research centers and referring institutions. An early planned biopsy would also facilitate timely inclusion of patients in biology-driven clinical trials. Ultimately, institution of multidisciplinary teams can optimize treatment choice, biopsy timing, and quick enrollment of patients in clinical trials, before their performance status deteriorates

Multisensory information facilitates reaction speed by enlarging activity difference between superior colliculus hemispheres in rats

Animals can make faster behavioral responses to multisensory stimuli than to unisensory stimuli. The superior colliculus (SC), which receives multiple inputs from different sensory modalities, is considered to be involved in the initiation of motor responses. However, the mechanism by which multisensory information facilitates motor responses is not yet understood. Here, we demonstrate that multisensory information modulates competition among SC neurons to elicit faster responses. We conducted multiunit recordings from the SC of rats performing a two-alternative spatial discrimination task using auditory and/or visual stimuli. We found that a large population of SC neurons showed direction-selective activity before the onset of movement in response to the stimuli irrespective of stimulation modality. Trial-by-trial correlation analysis showed that the premovement activity of many SC neurons increased with faster reaction speed for the contraversive movement, whereas the premovement activity of another population of neurons decreased with faster reaction speed for the ipsiversive movement. When visual and auditory stimuli were presented simultaneously, the premovement activity of a population of neurons for the contraversive movement was enhanced, whereas the premovement activity of another population of neurons for the ipsiversive movement was depressed. Unilateral inactivation of SC using muscimol prolonged reaction times of contraversive movements, but it shortened those of ipsiversive movements. These findings suggest that the difference in activity between the SC hemispheres regulates the reaction speed of motor responses, and multisensory information enlarges the activity difference resulting in faster responses

Testing Lorentz Invariance and CPT Conservation with NuMI Neutrinos in the MINOS Near Detector

A search for a sidereal modulation in the MINOS near detector neutrino data was performed. If present, this signature could be a consequence of Lorentz and CPT violation as predicted by a class of extensions to the Standard Model. No evidence for a sidereal signal in the data set was found, implying that there is no significant change in neutrino propagation that depends on the direction of the neutrino beam in a sun-centered inertial frame. Upper limits on the magnitudes of the Lorentz and CPT violating terms in these extensions to the Standard Model lie between 0.01-1% of the maximum expected, assuming a suppression of these signatures by factor of $10^{-17}$.

A Study of Muon Neutrino Disappearance Using the Fermilab Main Injector Neutrino Beam

We report the results of a search for muon-neutrino disappearance by the Main Injector Neutrino Oscillation Search. The experiment uses two detectors separated by 734 km to observe a beam of neutrinos created by the Neutrinos at the Main Injector facility at Fermi National Accelerator Laboratory. The data were collected in the first 282 days of beam operations and correspond to an exposure of 1.27e20 protons on target. Based on measurements in the Near Detector, in the absence of neutrino oscillations we expected 336 +/- 14 muon-neutrino charged-current interactions at the Far Detector but observed 215. This deficit of events corresponds to a significance of 5.2 standard deviations. The deficit is energy dependent and is consistent with two-flavor neutrino oscillations according to delta m-squared = 2.74e-3 +0.44/-0.26e-3 eV^2 and sin^2(2 theta) > 0.87 at 68% confidence level.Comment: In submission to Phys. Rev.

Measurement of the Atmospheric Muon Charge Ratio at TeV Energies with MINOS

The 5.4 kton MINOS far detector has been taking charge-separated cosmic ray muon data since the beginning of August, 2003 at a depth of 2070 meters-water-equivalent in the Soudan Underground Laboratory, Minnesota, USA. The data with both forward and reversed magnetic field running configurations were combined to minimize systematic errors in the determination of the underground muon charge ratio. When averaged, two independent analyses find the charge ratio underground to be 1.374 +/- 0.004 (stat.) +0.012 -0.010(sys.). Using the map of the Soudan rock overburden, the muon momenta as measured underground were projected to the corresponding values at the surface in the energy range 1-7 TeV. Within this range of energies at the surface, the MINOS data are consistent with the charge ratio being energy independent at the two standard deviation level. When the MINOS results are compared with measurements at lower energies, a clear rise in the charge ratio in the energy range 0.3 -- 1.0 TeV is apparent. A qualitative model shows that the rise is consistent with an increasing contribution of kaon decays to the muon charge ratio.Comment: 16 pages, 17 figure

Measurement of neutrino velocity with the MINOS detectors and NuMI neutrino beam

The velocity of a ~3 GeV neutrino beam is measured by comparing detection times at the near and far detectors of the MINOS experiment, separated by 734 km. A total of 473 far detector neutrino events was used to measure (v-c)/c=5.12.910-5 (at 68% C.L.). By correlating the measured energies of 258 charged-current neutrino events to their arrival times at the far detector, a limit is imposed on the neutrino mass of mnu&lt;50 MeV/c2 (99% C.L.)

First observations of separated atmospheric nu_mu and bar{nu-mu} events in the MINOS detector

The complete 5.4 kton MINOS far detector has been taking data since the beginning of August 2003 at a depth of 2070 meters water-equivalent in the Soudan mine, Minnesota. This paper presents the first MINOS observations of nuµ and [overline nu ]µ charged-current atmospheric neutrino interactions based on an exposure of 418 days. The ratio of upward- to downward-going events in the data is compared to the Monte Carlo expectation in the absence of neutrino oscillations, giving Rup/downdata/Rup/downMC=0.62-0.14+0.19(stat.)±0.02(sys.). An extended maximum likelihood analysis of the observed L/E distributions excludes the null hypothesis of no neutrino oscillations at the 98% confidence level. Using the curvature of the observed muons in the 1.3 T MINOS magnetic field nuµ and [overline nu ]µ interactions are separated. The ratio of [overline nu ]µ to nuµ events in the data is compared to the Monte Carlo expectation assuming neutrinos and antineutrinos oscillate in the same manner, giving R[overline nu ][sub mu]/nu[sub mu]data/R[overline nu ][sub mu]/nu[sub mu]MC=0.96-0.27+0.38(stat.)±0.15(sys.), where the errors are the statistical and systematic uncertainties. Although the statistics are limited, this is the first direct observation of atmospheric neutrino interactions separately for nuµ and [overline nu ]µ

Area-Wide Suppression of the Mediterranean Fruit Fly, Ceratitis capitata, and the Oriental Fruit Fly, Bactrocera dorsalis, in Kamuela, Hawaii

The United States Department of Agriculture's Agricultural Research Service initiated an area-wide fruit fly management program in Hawaii in 2000. The first demonstration site was established in Kamuela, Hawaii, USA. This paper documents suppression of the Mediterranean fruit fly, Ceratitis capitata (Wiedemann), and the oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae), in a 40 km2 area containing urban, rural and agricultural zones during a 6 year period. The suppression techniques included sanitation, GF-120 NF Naturalyte Fruit Fly Bait sprays, male annihilation, Biolure® traps, and parasitoids against C. capitata and B. dorsalis. In addition, small numbers of sterile males were released against B. dorsalis. Substantial reductions in fruit infestation levels were achieved for both species (90.7 and 60.7% for C. capitata and B. dorsalis, respectively) throughout the treatment period. Fruit fly captures in the 40 km2 treatment area were significantly lower during the 6 year period than those recorded in three non-treated areas. The strategy of combining suppression techniques in an area-wide approach is discussed