Sideromimic Modification of Lactivicin Dramatically Increases Potency against Extensively Drug-Resistant <i>Stenotrophomonas maltophilia </i>Clinical Isolates

Acetamido derivatives of the naturally antibacterial non-β-lactam lactivicin (LTV) have improved activity against their penicillin binding protein targets and reduced hydrolysis by β-lactamases, but penetration into Gram-negative bacteria is still relatively poor. Here we report that modification of the LTV lactone with a catechol-type siderophore increases potency 1,000-fold against Stenotrophomonas maltophilia, a species renowned for its insusceptibility to antimicrobials. The MIC90 of modified lactone compound 17 (LTV17) against a global collection of extensively drug-resistant clinical S. maltophilia isolates was 0.063 μg · ml(-1) Sideromimic modification does not reduce the ability of LTVs to induce production of the L1 and L2 β-lactamases in S. maltophilia and does not reduce the rate at which LTVs are hydrolyzed by L1 or L2. We conclude, therefore, that lactivicin modification with a siderophore known to be preferentially used by S. maltophilia substantially increases penetration via siderophore uptake. LTV17 has the potential to be developed as a novel antimicrobial for treatment of infections by S. maltophilia More generally, our work shows that sideromimic modification in a species-targeted manner might prove useful for the development of narrow-spectrum antimicrobials that have reduced collateral effects

Statistical properties of 12.2 GHz methanol masers associated with a complete sample of 6.7 GHz methanol masers

We present definitive detection statistics for 12.2 GHz methanol masers towards a complete sample of 6.7 GHz methanol masers detected in the Methanol Multibeam survey south of declination -20 degrees. In total, we detect 250 12.2 GHz methanol masers towards 580 6.7 GHz methanol masers. This equates to a detection rate of 43.1%, which is lower than that of previous significant searches of comparable sensitivity. Both the velocity ranges and the flux densities of the target 6.7 GHz sources surpass that of their 12.2 GHz companion in almost all cases. 80 % of the detected 12.2 GHz methanol maser peaks are coincident in velocity with the 6.7 GHz maser peak. Our data support an evolutionary scenario whereby the 12.2 GHz sources are associated with a somewhat later evolutionary stage than the 6.7 GHz sources devoid of this transition. Furthermore, we find that the 6.7 GHz and 12.2 GHz methanol sources increase in luminosity as they evolve. In addition to this, evidence for an increase in velocity range with evolution is presented. This implies that it is not only the luminosity, but also the volume of gas conducive to the different maser transitions, that increases as the sources evolve. Comparison with GLIMPSE mid-infrared sources has revealed a coincidence rate between the locations of the 6.7 GHz methanol masers and GLIMPSE point sources similar to that achieved in previous studies. Overall, the properties of the GLIMPSE sources with and without 12.2 GHz counterparts are similar. There is a higher 12.2 GHz detection rate towards those 6.7 GHz methanol masers that are coincident with extended green objects.Comment: Accepted to ApJ March 2011. 28 pages, 9 figure

Cargo Cults in Information Systems Development: a Definition and an Analytical Framework

Organizations today adopt agile information systems development methods (ISDM), but many do not succeed with the adoption process and in achieving desired results. Systems developers sometimes fail in efficient use of ISDM, often due to a lack of understanding the fundamental intentions of the chosen method. In many cases organizations simply imitate the behavior of others without really understanding why. This conceptual paper defines this phenomenon as an ISDM cargo cult behavior and proposes an analytical framework to identify such situations. The concept of cargo cults originally comes from the field of social anthropology and has been used to explain irrational, ritualistic imitation of certain behavior. By defining and introducing the concept in the field of information systems development we provide a diagnostic tool to better understand one of the reasons why ISDM adoption sometimes fail

12.2-GHz methanol maser MMB follow-up catalogue - I. Longitude range 330 to 10 degrees

We present a catalogue of 12.2-GHz methanol masers detected towards 6.7-GHz methanol masers observed in the unbiased Methanol Multibeam (MMB) survey in the longitude range 330\circ (through 360\circ) to 10\circ. This is the first portion of the catalogue which, when complete, will encompass all of the MMB detections. We report the detection of 184 12.2-GHz sources towards 400 6.7-GHz methanol maser targets, equating to a detection rate of 46 per cent. Of the 184 12.2-GHz detections, 117 are reported here for the first time. We draw attention to a number of 'special' sources, particularly those with emission at 12.2-GHz stronger than their 6.7-GHz counterpart and conclude that these unusual sources are not associated with a specific evolutionary stage.Comment: accepted to MNRAS 21 Dec 201

Methods for Fine Scale Functional Imaging of Tactile Motion in Human and Nonhuman Primates

In the visual and auditory systems specialized neural pathways use motion cues to track object motion and self-motion, and use differential motion cues for figure-ground segregation. To examine the neural circuits that encode motion in the somatosensory system, we have developed neuroimaging methods to study motion processing in human and nonhuman primates. We have implemented stimulus presentation paradigms to examine neural encoding of apparent motion percepts. These paradigms are designed to be compatible with fMRI, optical imaging, and electrophysiological methods, thereby permitting direct comparison of data derived across neurofunctional scales. An additional motivation for using a common tactile motion stimulation paradigm is to bridge two disparate bodies of work, that derived from neuroimaging studies in humans and another from neuroimaging, neurophysiological and neuroanatomical studies in monkeys. Here, we demonstrate that such an approach through the use of optical imaging and 9.4 Tesla fMRI experiments in monkeys, and 7 Tesla fMRI experiments in humans is effective in revealing neural regions activated by tactile motion stimuli. These methods span spatial scales capable of detecting 100 μm sized domains to those that would reveal global whole brain circuits. Armed with such capabilities, our long-term goals are to identify directionally selective areas and directionally se-lective functional domains and understand the global pathways within which they reside. Such knowledge would have great impact on our thinking regarding not only tactile motion processing, but also general strategies underlying somatosensory cortical processing

The SQUALO project (Star formation in QUiescent And Luminous Objects) I: clump-fed accretion mechanism in high-mass star-forming objects

The formation mechanism of the most massive stars is far from completely understood. It is still unclear if the formation is core-fed or clump-fed, i.e. if the process is an extension of what happens in low-mass stars, or if the process is more dynamical such as a continuous, multiscale accretion from the gas at parsec (or even larger) scales. In this context, we introduce the SQUALO project, an ALMA 1.3 and 3 mm survey designed to investigate the properties of 13 massive clumps selected at various evolutionary stages, with the common feature that they all show evidence for accretion at the clump scale. In this work, we present the results obtained from the 1.3 mm continuum data. Our observations identify 55 objects with masses in the range 0.4 ≤ M ≤ 309 M☉, with evidence that the youngest clumps already present some degree of fragmentation. The data show that physical properties such as mass and surface density of the fragments and their parent clumps are tightly correlated. The minimum distance between fragments decreases with evolution, suggesting a dynamical scenario in which massive clumps first fragment under the influence of non-thermal motions driven by the competition between turbulence and gravity. With time gravitational collapse takes over and the fragments organize themselves into more thermally supported objects while continuing to accrete from their parent clump. Finally, one source does not fragment, suggesting that the support of other mechanisms (such as magnetic fields) is crucial only in specific star-forming regions. © 2023 The Author(s) Published by Oxford University Press on behalf of Royal Astronomical Society.This paper makes use of the following ALMA data: ADS/JAO.ALMA#2018.1.00443.S. ALMA is a partnership of ESO (representing its member states), NSF (USA) and NINS (Japan), together with NRC (Canada), MOST and ASIAA (Taiwan), and KASI (Republic of Korea), in cooperation with the Republic of Chile. The Joint ALMA Observatory is operated by ESO, AUI/NRAO, and NAOJ. AT gratefully acknowledges support from a mini-grant funded by INAF. AT acknowledges support from the European Research Council Synergy Grant ECOGAL (Grant: 855130). AA acknowledges support from STFC grants ST/T001488/1 and ST/P000827/1. GAF acknowledges support from the Collaborative Research Centre 956, funded by the Deutsche Forschungsgemeinschaft (DFG) project ID 184018867. GAF also acknowledges financial support from the State Agency for Research of the Spanish MCIU through the AYA 2017-84390-C2-1-R grant (co-funded by FEDER) and through the Center of Excellence Severo Ochoa' award for the Instituto de Astrofisica de Andalucia (SEV-2017-0709). RJS acknowledges funding from an STFC ERF (grant ST/N00485X/1) and HPC from the DiRAC facility (ST/P002293/1). TGSP gratefully acknowledges support by the National Science Foundation under grant No. AST-2009842 and AST-2108989

12.2-GHz methanol maser MMB follow-up catalogue - II. Longitude range 186 to 330 degrees

We present the second portion of a catalogue of 12.2-GHz methanol masers detected towards 6.7-GHz methanol masers observed in the unbiased Methanol Multibeam (MMB) Survey. Using the Parkes radio telescope we have targeted all 207 6.7-GHz methanol masers in the longitude range 186 to 330 degrees for 12.2-GHz counterparts. We report the detection of 83 12.2-GHz methanol masers, and one additional source which we suspect is thermal emission, equating to a detection rate of 40 per cent. Of the 83 maser detections, 39 are reported here for the first time. We discuss source properties, including variability and highlight a number of unusual sources. We present a list of 45 candidates that are likely to harbor methanol masers in the 107.0-GHz transition.Comment: Accepted MNRAS 19 July 201