In this paper, we present the first observations of the Ophiuchus molecular cloud performed as part of the James Clerk Maxwell Telescope (JCMT) Gould Belt Survey (GBS) with the SCUBA-2 instrument. We ...demonstrate methods for combining these data with previous HARP CO, Herschel, and IRAM N2H+ observations in order to accurately quantify the properties of the SCUBA-2 sources in Ophiuchus. We produce a catalogue of all of the sources found by SCUBA-2. We separate these into protostars and starless cores. We list all of the starless cores and perform a full virial analysis, including external pressure. This is the first time that external pressure has been included in this level of detail. We find that the majority of our cores are either bound or virialized. Gravitational energy and external pressure are on average of a similar order of magnitude, but with some variation from region to region. We find that cores in the Oph A region are gravitationally bound prestellar cores, while cores in the Oph C and E regions are pressure-confined. We determine that N2H+ is a good tracer of the bound material of prestellar cores, although we find some evidence for N2H+ freeze-out at the very highest core densities. We find that non-thermal linewidths decrease substantially between the gas traced by C18O and that traced by N2H+, indicating the dissipation of turbulence at higher densities. We find that the critical Bonnor–Ebert stability criterion is not a good indicator of the boundedness of our cores. We detect the pre-brown dwarf candidate Oph B-11 and find a flux density and mass consistent with previous work. We discuss regional variations in the nature of the cores and find further support for our previous hypothesis of a global evolutionary gradient across the cloud from south-west to north-east, indicating sequential star formation across the region.
Antibody-drug conjugates (ADC) utilizing noncleavable linker drugs have been approved for clinical use, and several are in development targeting solid and hematologic malignancies including multiple ...myeloma. Currently, there are no reliable biomarkers of activity for these ADCs other than presence of the targeted antigen. We observed that certain cell lines are innately resistant to such ADCs, and sought to uncover the underlying mechanism of resistance.
The expression of 43 lysosomal membrane target genes was evaluated in cell lines resistant to ADCs bearing the noncleavable linker, pyrrolobenzodiazepine payload SG3376,
. The functional relevance of SLC46A3, a lysosomal transporter of noncleavable ADC catabolites whose expression uniquely correlated with SG3376 resistance, was assessed using EPHA2-, HER2-, and BCMA-targeted ADCs and isogenic cells overexpressing or genetically inactivated for
.
expression was also examined in patient-derived xenograft and
models of acquired T-DM1 resistance and multiple myeloma bone marrow samples by RT-PCR.
Loss of
expression was found to be a mechanism of innate and acquired resistance to ADCs bearing DM1 and SG3376. Sensitivity was restored in refractory lines upon introduction of
, suggesting that expression of
may be more predictive of activity than target antigen levels alone. Interrogation of primary multiple myeloma samples indicated a range of
expression, including samples with undetectable levels like multiple myeloma cell lines resistant to BCMA-targeting DM1 and SG3376 ADCs.
Our findings support
as a potential patient selection biomarker with immediate relevance to clinical trials involving these ADCs.
Primal‐Dual Optimization for Fluids Inglis, T.; Eckert, M.‐L.; Gregson, J. ...
Computer graphics forum,
December 2017, Letnik:
36, Številka:
8
Journal Article
Recenzirano
Odprti dostop
We apply a novel optimization scheme from the image processing and machine learning areas, a fast Primal‐Dual method, to achieve controllable and realistic fluid simulations. While our method is ...generally applicable to many problems in fluid simulations, we focus on the two topics of fluid guiding and separating solid‐wall boundary conditions. Each problem is posed as an optimization problem and solved using our method, which contains acceleration schemes tailored to each problem. In fluid guiding, we are interested in partially guiding fluid motion to exert control while preserving fluid characteristics. With our method, we achieve explicit control over both large‐scale motions and small‐scale details which is valuable for many applications, such as level‐of‐detail adjustment (after running the coarse simulation), spatially varying guiding strength, domain modification, and resimulation with different fluid parameters. For the separating solid‐wall boundary conditions problem, our method effectively eliminates unrealistic artefacts of fluid crawling up solid walls and sticking to ceilings, requiring few changes to existing implementations. We demonstrate the fast convergence of our Primal‐Dual method with a variety of test cases for both model problems.
We apply a novel optimization scheme from the image processing and machine learning areas, a fast Primal‐Dual method, to achieve controllable and realistic fluid simulations. While our method is generally applicable to many problems in fluid simulations, we focus on the two topics of fluid guiding and separating solid‐wall boundary conditions. Each problem is posed as an optimization problem and solved using our method, which contains acceleration schemes tailored to each problem.
We present observations of the Cepheus Flare obtained as part of the James Clerk Maxwell Telescope (JCMT) Gould Belt Legacy Survey (GBLS) with the SCUBA-2 instrument. We produce a catalogue of ...sources found by SCUBA-2, and separate these into starless cores and protostars. We determine masses and densities for each of our sources, using source temperatures determined by the Herschel Gould Belt Survey. We compare the properties of starless cores in four different molecular clouds: L1147/58, L1172/74, L1251 and L1228. We find that the core mass functions for each region typically show shallower-than-Salpeter behaviour. We find that L1147/58 and L1228 have a high ratio of starless cores to Class II protostars, while L1251 and L1174 have a low ratio, consistent with the latter regions being more active sites of current star formation, while the former are forming stars less actively. We determine that if modelled as thermally supported Bonnor-Ebert spheres, most of our cores have stable configurations accessible to them. We estimate the external pressures on our cores using archival 13CO velocity dispersion measurements and find that our cores are typically pressure confined, rather than gravitationally bound. We perform a virial analysis on our cores, and find that they typically cannot be supported against collapse by internal thermal energy alone, due primarily to the measured external pressures. This suggests that the dominant mode of internal support in starless cores in the Cepheus Flare is either non-thermal motions or internal magnetic fields.
We present 450 and 850 m submillimeter continuum observations of the IC 5146 star-forming region taken as part of the James Clerk Maxwell Telescope Gould Belt Survey. We investigate the location of ...bright submillimeter (clumped) emission with the larger-scale molecular cloud through comparison with extinction maps, and find that these denser structures correlate with higher cloud column density. Ninety-six individual submillimeter clumps are identified using FellWalker, and their physical properties are examined. These clumps are found to be relatively massive, ranging from 0.5 to 116 with a mean mass of 8 and a median mass of 3.7 . A stability analysis for the clumps suggests that the majority are (thermally) Jeans stable, with . We further compare the locations of known protostars with the observed submillimeter emission, finding that younger protostars, i.e., Class 0 and I sources, are strongly correlated with submillimeter peaks and that the clumps with protostars are among the most Jeans unstable. Finally, we contrast the evolutionary conditions in the two major star-forming regions within IC 5146: the young cluster associated with the Cocoon Nebula and the more distributed star formation associated with the Northern Streamer filaments. The Cocoon Nebula appears to have converted a higher fraction of its mass into dense clumps and protostars, the clumps are more likely to be Jeans unstable, and a larger fraction of these remaining clumps contain embedded protostars. The Northern Streamer, however, has a larger number of clumps in total and a larger fraction of the known protostars are still embedded within these clumps.
Abstract
Background
M184V/I cause high-level lamivudine (3TC) and emtricitabine (FTC) resistance and increased tenofovir disoproxil fumarate (TDF) susceptibility. Nonetheless, 3TC and FTC ...(collectively referred to as XTC) appear to retain modest activity against human immunodeficiency virus-1 with these mutations possibly as a result of reduced replication capacity. In this study, we determined how M184V/I impacts virus load (VL) in patients failing therapy on a TDF/XTC plus nonnucleoside reverse-transcriptase inhibitor (NNRTI)-containing regimen.
Methods
We compared VL in the absence and presence of M184V/I across studies using random effects meta-analysis. The effect of mutations on virus reverse-transcriptase activity and infectiousness was analyzed in vitro.
Results
M184I/V was present in 817 (56.5%) of 1445 individuals with virologic failure (VF). Virus load was similar in individuals with or without M184I/V (difference in log10 VL, 0.18; 95% confidence interval, .05–.31). CD4 count was lower both at initiation of antiretroviral therapy and at VF in participants who went on to develop M184V/I. L74I was present in 10.2% of persons with M184V/I but absent in persons without M184V/I (P < .0001). In vitro, L74I compensated for defective replication of M184V-mutated virus.
Conclusions
Virus loads were similar in persons with and without M184V/I during VF on a TDF/XTC/NNRTI-containing regimen. Therefore, we did not find evidence for a benefit of XTC in the context of first-line failure on this combination.
Lamivudine is a cornerstone antiretroviral whose efficacy has been ascribed to high fitness cost of the lamivudine resistance mutation M184V. However, here we demonstrate elevated viral loads in the context of M184V, likely attributable to compensatory mutations such as L74I.
ABSTRACT The dust emissivity spectral index, β, is a critical parameter for deriving the mass and temperature of star-forming structures and, consequently, their gravitational stability. The β value ...is dependent on various dust grain properties, such as size, porosity, and surface composition, and is expected to vary as dust grains evolve. Here we present β, dust temperature, and optical depth maps of the star-forming clumps in the Perseus Molecular Cloud determined from fitting spectral energy distributions to combined Herschel and JCMT observations in the 160, 250, 350, 500, and 850 m bands. Most of the derived β and dust temperature values fall within the ranges of 1.0-2.7 and 8-20 K, respectively. In Perseus, we find the β distribution differs significantly from clump to clump, indicative of grain growth. Furthermore, we also see significant localized β variations within individual clumps and find low-β regions correlate with local temperature peaks, hinting at the possible origins of low-β grains. Throughout Perseus, we also see indications of heating from B stars and embedded protostars, as well evidence of outflows shaping the local landscape.
We employ SCUBA-2 (Submillimetre Common-User Bolometer Array 2) observations of the Orion A North molecular cloud to derive column density and temperature maps. We apply a novel, Hessian-based ...structural identification algorithm for detection of prestellar cores to these data, allowing for automated generation of the prestellar mass function. The resulting mass function is observed to peak at
$1.39^{+0.18}_{-0.19}$
M⊙, indicating a star-forming efficiency lower limit of ∼14 per cent when compared with the Orion nebula Cluster initial mass function (IMF) peak. Additionally, the prestellar mass function is observed to decay with a high-mass power-law exponent
$\alpha =2.53^{+0.16}_{-0.14}$
, indicating approximate functional similarity with the Salpeter IMF (α = 2.35). This result, when combined with the results of previous investigations suggests a regional dependence of the star-forming efficiency.
Prevalence of spasticity post stroke Watkins, C L; Leathley, M J; Gregson, J M ...
Clinical rehabilitation,
08/2002, Letnik:
16, Številka:
5
Journal Article
Recenzirano
Objectives: To establish the prevalence of spasticity 12 months after stroke and examine its relationship with functional ability.
Design: A cohort study of prevalence of spasticity at 12 months post ...stroke. Setting: Initially hospitalized but subsequently community-dwelling stroke survivors in Liverpool, UK.
Subjects: One hundred and six consecutively presenting stroke patients surviving to 12 months.
Main outcome measures: Muscle tone measured at the elbow using the Modi”ed Ashworth Scale and at several joints, in the arms and legs, using the Tone Assessment Scale; functional ability using the modi”ed Barthel Index.
Results: Increased muscle tone (spasticity) was present in 29 (27%) and 38 (36%) of the 106 patients when measured using the Modi”ed Ashworth Scale and Tone Assessment Scale respectively. Combining the results from both scales produced a prevalence of 40 (38%). Those with spasticity had signi”cantly lower Barthel scores at 12 months (p < 0.0001).
Conclusion: When estimating the prevalence of spasticity it is essential to assess both arms and legs, using both scales. Despite measuring tone at several joints, spasticity was demonstrated in only 40 (38%) patients, lower than previous estimates.
We present the JCMT Gould Belt Survey's first look results of the southern extent of the Orion A Molecular Cloud (δ ≤ −5:31:27.5). Employing a two-step structure identification process, we construct ...individual catalogues for large-scale regions of significant emission labelled as islands and smaller-scale subregions called fragments using the 850 μm continuum maps obtained using SCUBA-2. We calculate object masses, sizes, column densities, and concentrations. We discuss fragmentation in terms of a Jeans instability analysis and highlight interesting structures as candidates for follow-up studies. Furthermore, we associate the detected emission with young stellar objects (YSOs) identified by Spitzer and Herschel. We find that although the population of active star-forming regions contains a wide variety of sizes and morphologies, there is a strong positive correlation between the concentration of an emission region and its calculated Jeans instability. There are, however, a number of highly unstable subregions in dense areas of the map that show no evidence of star formation. We find that only ∼72 per cent of the YSOs defined as Class 0+I and flat-spectrum protostars coincide with dense 850 μm emission structures (column densities >3.7 × 1021 cm−2). The remaining 28 per cent of these objects, which are expected to be embedded in dust and gas, may be misclassified. Finally, we suggest that there is an evolution in the velocity dispersion of YSOs such that sources which are more evolved are associated with higher velocities.
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