Mycobacterium tuberculosis is an old enemy of the human race, with evidence of infection observed as early as 5000 years ago. Although more host-restricted than Mycobacterium bovis, which can infect ...all warm-blooded vertebrates, M. tuberculosis can infect, and cause morbidity and mortality in, several veterinary species as well. As M. tuberculosis is one of the earliest described bacterial pathogens, the literature describing this organism is vast and overwhelming. This review strives to distill what is currently known about this bacterium and the disease it causes for the veterinary pathologist.
In many tokamak and stellarator experiments around the globe that are investigating energy production via controlled thermonuclear fusion, electron cyclotron heating and current drive (ECH&CD) are ...used for plasma start-up, heating, non-inductive current drive and magnetohydrodynamic stability control. ECH will be the first auxiliary heating method used on ITER. Megawatt-class, continuous wave gyrotrons are employed as high-power millimeter (mm)-wave sources. The present review reports on the worldwide state-of-the-art of high-power gyrotrons. Their successful development during recent years changed ECH from a minor to a major heating method. After a general introduction of the various functions of ECH&CD in fusion physics, especially for ITER, section 2 will explain the fast-wave gyrotron interaction principle. Section 3 discusses innovations on the components of modern long-pulse fusion gyrotrons (magnetron injection electron gun, beam tunnel, cavity, quasi-optical output coupler, synthetic diamond output window, single-stage depressed collector) and auxiliary components (superconducting magnets, gyrotron diagnostics, high-power calorimetric dummy loads). Section 4 deals with present megawatt-class gyrotrons for ITER, W7-X, LHD, EAST, KSTAR and JT-60SA, and also includes tubes for moderate pulse length machines such as ASDEX-U, DIII-D, HL-2A, TCV, QUEST and GAMMA-10. In section 5 the development of future advanced fusion gyrotrons is discussed. These are tubes with higher frequencies for DEMO, multi-frequency (multi-purpose) gyrotrons, stepwise frequency tunable tubes for plasma stabilization, injection-locked and coaxial-cavity multi-megawatt gyrotrons, as well as sub-THz gyrotrons for collective Thomson scattering. Efficiency enhancement via multi-stage depressed collectors, fast oscillation recovery methods and reliability, availability, maintainability and inspectability will be discussed at the end of this section.
This study aimed to evaluate the effects of triglycerides containing medium-chain fatty acids (MCT) and tributyrin (TB) supplementation in a milk replacer (MR) on growth performance, plasma ...metabolites, and hormone concentrations in dairy calves. Sixty-three Holstein heifer calves (body weight at 8 d of age, 41.1 ± 2.91 kg; mean ± SD) were randomly assigned to 1 of 4 experimental MR (28% crude protein and 18% fat): (1) containing 3.2% C8:0 and 2.8% C10:0 (in fat basis) without TB supplementation (CONT; n = 15), (2) containing 6.7% C8:0 and 6.4% C10:0 without TB supplementation (MCT; n = 16), (3) containing 3.2% C8:0 and 2.8% C10:0 with 0.6% (dry matter basis) TB supplementation (CONT+TB; n = 16), (4) containing 6.7% C8:0 and 6.4% C10:0 with 0.6% TB supplementation (MCT+TB; n = 16). The MR were offered at 600 g/d (powder basis) from 8 to 14 d, up to 1,300 g/d from 15 to 21 d, 1,400 g/d from 22 to 49 d, down to 700 g/d from 50 to 56 d, 600 g/d from 57 to 63 d, and weaned at 64 d of age. All calves were fed calf starter, chopped hay, and water ad libitum. The data were analyzed using a 2-way ANOVA via the fit model procedure of JMP Pro 16 (SAS Institute Inc.). Medium-chain fatty acid supplementation did not affect the total dry matter intake. However, calves that were fed MCT had greater feed efficiency (gain/feed) before weaning (0.74 ± 0.098 vs. 0.71 ± 0.010 kg/kg) compared with non-MCT calves. The MCT calves also had a lower incidence of diarrhea compared with non-MCT calves during 23 to 49 d of age and the weaning period (50 to 63 d of age; 9.2% vs. 18.5% and 10.5% vs. 17.2%, respectively). Calves fed with TB had a greater total dry matter intake during postweaning (3,465 vs. 3,232 g/d). Calves fed TB also had greater body weight during the weaning (90.7 ± 0.97 vs. 87.9 ± 1.01 kg) and postweaning period (116.5 ± 1.47 vs. 112.1 ± 1.50 kg) compared with that of non-TB calves. The plasma metabolites and hormone concentrations were not affected by MCT or TB. These results suggest that MCT and TB supplementation in the MR may improve the growth performance and gut health of dairy calves.
We report Atacama Large Millimeter/submillimeter Array (ALMA) observations of CO(3-2) emission in a sample of seven Seyfert/LINER galaxies at the unprecedented spatial resolution of 0.″1 = 4−8 0 . ″ ...1 = 4 − 9 $ 0 {{\overset{\prime\prime}{.}}}1=4{-}9 $ pc. Our aim is to explore the close environment of active galactic nuclei (AGN), and the dynamical structures leading to their fueling, through the morphology and kinematics of the gas inside the sphere of influence of the black hole. The selected galaxies host low-luminosity AGN and have a wide range of activity types (Seyferts 1 to 2, LINERs), and barred or ringed morphologies. The observed maps reveal the existence of circumnuclear disk structures, defined by their morphology and decoupled kinematics, in most of the sample. We call these structures molecular tori, even though they often appear as disks without holes in the center. They have varying orientations along the line of sight, unaligned with the host galaxy orientation. The radius of the tori ranges from 6 to 27 pc, and their mass from 0.7 × 107 to 3.9 × 107 M⊙. The most edge-on orientations of the torus correspond to obscured Seyferts. In only one case (NGC 1365), the AGN is centered on the central gas hole of the torus. On a larger scale, the gas is always piled up in a few resonant rings 100 pc in scale that play the role of a reservoir to fuel the nucleus. In some cases, a trailing spiral is observed inside the ring, providing evidence for feeding processes. More frequently, the torus and the AGN are slightly off-centered with respect to the bar-resonant ring position, implying that the black hole is wandering by a few 10 pc amplitude around the center of mass of the galaxy. Our spatial resolution allows us to measure gas velocities inside the sphere of influence of the central black holes. By fitting the observations with different simulated cubes, varying the torus inclination and the black hole mass, it is possible to estimate the mass of the central black hole, which is in general difficult for such late-type galaxies, with only a pseudo-bulge. In some cases, AGN feedback is revealed through a molecular outflow, which will be studied in detail in a subsequent article.
Context. Observations of chemical species can provide insights into the physical conditions of the emitting gas however it is important to understand how their abundances and excitation vary within ...different heating environments. C2H is a molecule typically found in PDR regions of our own Galaxy but there is evidence to suggest it also traces other regions undergoing energetic processing in extragalactic environments. Aims. As part of the ALCHEMI ALMA large program, we map the emission of C2H in the central molecular zone of the nearby starburst galaxy NGC 253 at 1.6″ (28 pc) resolution and characterize it to understand its chemical origins. Methods. We used spectral modeling of the N = 1−0 through N = 4−3 rotational transitions of C2H to derive the C2H column densities towards the dense clouds in NGC 253. We then use chemical modeling, including photodissociation region (PDR), dense cloud, and shock models to investigate the chemical processes and physical conditions that are producing the molecular emission. Results. We find high C2H column densities of ∼1015 cm−2 detected towards the dense regions of NGC 253. We further find that these column densities cannot be reproduced if it is assumed that the emission arises from the PDR regions at the edge of the clouds. Instead, we find that the C2H abundance remains high even in the high visual extinction interior of these clouds and that this is most likely caused by a high cosmic-ray ionization rate.
Proteolysis targeting chimeric molecules (Protacs) target proteins for destruction by exploiting the ubiquitin-dependent proteolytic system of eukaryotic cells. We designed two Protacs that contain ...the peptide 'degron' from hypoxia-inducible factor-1alpha, which binds to the Von-Hippel-Lindau (VHL) E3 ubiquitin ligase complex, linked to either dihydroxytestosterone that targets the androgen receptor (AR; Protac-A), or linked to estradiol (E2) that targets the estrogen receptor-alpha (ERalpha; Protac-B). We hypothesized that these Protacs would recruit hormone receptors to the VHL E3 ligase complex, resulting in the degradation of receptors, and decreased proliferation of hormone-dependent cell lines. Treatment of estrogen-dependent breast cancer cells with Protac-B induced the degradation of ERalpha in a proteasome-dependent manner. Protac-B inhibited the proliferation of ERalpha-dependent breast cancer cells by inducing G(1) arrest, inhibition of retinoblastoma phosphorylation and decreasing expression of cyclin D1, progesterone receptors A and B. Protac-B treatment did not affect the proliferation of estrogen-independent breast cancer cells that lacked ERalpha expression. Similarly, Protac-A treatment of androgen-dependent prostate cancer cells induced G(1) arrest but did not affect cells that do not express AR. Our results suggest that Protacs specifically inhibit the proliferation of hormone-dependent breast and prostate cancer cells through degradation of the ERalpha and AR, respectively.
Minocycline is commonly used to inhibit microglial activation. It is widely accepted that activated microglia exert dual functions, that is, pro-inflammatory (M1) and anti-inflammatory (M2) ...functions. The in vivo status of activated microglia is probably on a continuum between these two extreme states. However, the mechanisms regulating microglial polarity remain elusive. Here, we addressed this question focusing on minocycline. We used SOD1(G93A) mice as a model, which exhibit the motor neuron-specific neurodegenerative disease, amyotrophic lateral sclerosis. Administration of minocycline attenuated the induction of the expression of M1 microglia markers during the progressive phase, whereas it did not affect the transient enhancement of expression of M2 microglia markers during the early pathogenesis phase. This selective inhibitory effect was confirmed using primary cultured microglia stimulated by lipopolysaccharide (LPS) or interleukin (IL)-4, which induced M1 or M2 polarization, respectively. Furthermore, minocycline inhibited the upregulation of NF-κB in the LPS-stimulated primary cultured microglia and in the spinal cord of SOD1(G93A) mice. On the other hand, IL-4 did not induce upregulation of NF-κB. This study indicates that minocycline selectively inhibits the microglia polarization to a proinflammatory state, and provides a basis for understanding pathogeneses of many diseases accompanied by microglial activation.
Submillimetre and millimetre line and continuum observations are important in probing the morphology, column density, and dynamics of the molecular gas and dust around obscured active galactic nuclei ...(AGNs) and their mechanical feedback. With very high-resolution (0.″02 × 0.″03 (2 × 3 pc)) ALMA 345 GHz observations of CO 3–2, HCO
+
4–3, vibrationally excited HCN 4–3
ν
2
= 1
f
, and continuum we have studied the remarkable, extremely radio-quiet, molecular jet and wind of the lenticular galaxy NGC 1377. The outflow structure is resolved, revealing a 150 pc long, clumpy, high-velocity (∼600 km s
−1
), collimated molecular jet where the molecular emission is emerging from the spine of the jet with an average diameter of 3–7 pc. The jet widens to 10–15 pc about 25 pc from the centre, which is possibly due to jet-wind interactions. A narrow-angle (50°–70°), misaligned and rotating molecular wind surrounds the jet, and both are enveloped by a larger-scale CO-emitting structure at near-systemic velocity. The jet and narrow wind have steep radial gas excitation gradients and appear turbulent with high gas dispersion (
σ
> 40 km s
−1
). The jet shows velocity reversals that we propose are caused by precession, or more episodic directional changes. We discuss the mechanisms powering the outflow, and we find that an important process for the molecular jet and narrow wind is likely magneto-centrifugal driving. In contrast, the large-scale CO-envelope may be a slow wind, or cocoon that stems from jet-wind interactions. An asymmetric, nuclear
r
∼ 2 pc dust structure with a high inferred molecular column density
N
(H
2
) ≃1.8 × 10
24
cm
−2
is detected in continuum and also shows compact emission from vibrationally excited HCN. The nuclear dust emission is hot (
T
d
> 180 K) and its luminosity is likely powered by a buried AGN. The lopsided structure appears to be a warped disk, which is responsible for a significant part of the nuclear obscuration and possibly formed as a result of uneven gas inflows. The dynamical mass inside
r
= 1.4 pc is estimated to 9
−3
+2
× 10
6
M
⊙
, implying that the supermassive black hole (SMBH) has a high mass with respect to the stellar velocity dispersion of NGC 1377. We suggest that the SMBH of NGC 1377 is currently in a state of moderate growth, at the end of a more intense phase of accretion and also evolving from a state of more extreme nuclear obscuration. The nuclear growth may be fuelled by low-angular momentum gas inflowing from the gas ejected in the molecular jet and wind. Such a feedback-loop of cyclic outflows and central accretion could explain why there is still a significant reservoir of molecular gas in this ageing, lenticular galaxy. A feedback-loop would be an effective process in growing the nuclear SMBH and thus would constitute an important phase in the evolution of NGC 1377. This also invites new questions as to SMBH growth processes in obscured, dusty galaxies.
With high resolution (0.̋25 × 0.̋18) ALMA CO 3−2 (345 GHz) observations of the nearby (D = 21 Mpc, 1′′ = 102 pc), extremely radio-quiet galaxy NGC 1377, we have discovered a high-velocity, very ...collimated nuclear outflow which we interpret as a molecular jet with a projected length of ±150 pc. The launch region is unresolved and lies inside a radius r< 10 pc. Along the jet axis we find strong velocity reversals where the projected velocity swings from −150km s-1 to +150 km s-1. A simple model of a molecular jet precessing around an axis close to the plane of the sky can reproduce the observations. The velocity of the outflowing gas is difficult to constrain due to the velocity reversals but we estimate it to be between 240 and 850 km s-1 and the jet to precess with a period P = 0.3−1.1 Myr. The CO emission is clumpy along the jet and the total molecular mass in the high-velocity (±(60 to 150 km s-1)) gas lies between 2 × 106M⊙ (light jet) and 2 × 107M⊙ (massive jet). There is also CO emission extending along the minor axis of NGC 1377. It holds > 40% of the flux in NGC 1377 and may be a slower, wide-angle molecular outflow which is partially entrained by the molecular jet. We discuss the driving mechanism of the molecular jet and suggest that it is either powered by a (faint) radio jet or by an accretion disk-wind similar to those found towards protostars. It seems unlikely that a massive jet could have been driven out by the current level of nuclear activity which should then have undergone rapid quenching. The light jet would only have expelled 10% of the inner gas and may facilitate nuclear activity instead of suppressing it. The nucleus of NGC 1377 harbours intense embedded activity and we detect emission from vibrationally excited HCN J = 4−3ν2 = 1f which is consistent with hot gas and dust. We find large columns of H2 in the centre of NGC 1377 which may be a sign of a high rate of recent gas infall. The dynamical age ofthe molecular jet is short (<1 Myr), which could imply that it is young and consistent with the notion that NGC 1377 is caught in a transient phase of its evolution. However, further studies are required to determine the age of the molecular jet, its mass and the role it is playing in the growth of the nucleus of NGC 1377.
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