A Test of the Standard Hypothesis for the Origin of the HI Holes in Holmberg II

The nearby irregular galaxy Holmberg II has been extensively mapped in HI using the Very Large Array (VLA), revealing intricate structure in its interstellar gas component (Puche et al. 1992). An analysis of these structures shows the neutral gas to contain a number of expanding HI holes. The formation of the HI holes has been attributed to multiple supernova events occurring within wind-blown shells around young, massive star clusters, with as many as 10-200 supernovae required to produce many of the holes. From the sizes and expansion velocities of the holes, Puche et al. assigned ages of ~10^7 to 10^8 years. If the supernova scenario for the formation of the HI holes is correct, it implies the existence of star clusters with a substantial population of late-B, A and F main sequence stars at the centers of the holes. Many of these clusters should be detectable in deep ground-based CCD images of the galaxy. In order to test the supernova hypothesis for the formation of the HI holes, we have obtained and analyzed deep broad-band BVR and narrow-band H-alpha images of Ho II. We compare the optical and HI data and search for evidence of the expected star clusters in and around the HI holes. We also use the HI data to constrain models of the expected remnant stellar population. We show that in several of the holes the observed upper limits for the remnant cluster brightness are strongly inconsistent with the SNe hypothesis described in Puche et al. Moreover, many of the HI holes are located in regions of very low optical surface brightness which show no indication of recent star formation. Here we present our findings and explore possible alternative explanations for the existence of the HI holes in Ho II, including the suggestion that some of the holes were produced by Gamma-ray burst events.Comment: 30 pages, including 6 tables and 3 images. To appear in Astron. Journal (June 1999

The Arabidopsis KH-Domain RNA-Binding Protein ESR1 Functions in Components of Jasmonate Signalling, Unlinking Growth Restraint and Resistance to Stress

Glutathione S-transferases (GSTs) play important roles in the protection of cells against toxins and oxidative damage where one Arabidopsis member, GSTF8, has become a commonly used marker gene for early stress and defense responses. A GSTF8 promoter fragment fused to the luciferase reporter gene was used in a forward genetic screen for Arabidopsis mutants with up-regulated GSTF8 promoter activity. This identified the esr1-1 (enhanced stress response 1) mutant which also conferred increased resistance to the fungal pathogen Fusarium oxysporum. Through positional cloning, the ESR1 gene was found to encode a KH-domain containing RNA-binding protein (At5g53060). Whole transcriptome sequencing of esr1-1 identified altered expression of genes involved in responses to biotic and abiotic stimuli, hormone signaling pathways and developmental processes. In particular was an overall significant enrichment for jasmonic acid (JA) mediated processes in the esr1-1 down-regulated dataset. A subset of these genes were tested for MeJA inducibility and we found the expression of some but not all were reduced in esr1-1. The esr1-1 mutant was not impaired in other aspects of JA-signalling such as JA- sensitivity or development, suggesting ESR1 functions in specific components of the JA-signaling pathway. Examination of salicylic acid (SA) regulated marker genes in esr1-1 showed no increase in basal or SA induced expression suggesting repression of JA-regulated genes is not due to antagonistic SA-JA crosstalk. These results define new roles for KH-domain containing proteins with ESR1 unlinking JA-mediated growth and defense responses.http://doi.org/10.1371/journal.pone.0126978</a

Development of extractive distillation processes for close-boiling polar systems

Extractive distillation is a distillation technique that can be applied for separation of azeotropic mixtures and mixtures of close-boiling compounds. In extractive distillation a solvent is applied to increase the relative volatility by interacting with the components in the system, typically with a difference in affinity for the components. To study the relation between the affinity strength and the effect of the solvent on the relative volatility, the research here presented focused on a solvent selection for the separation of two close-boiling, highly polar binary systems. 1) The acids valeric acid and its isomer 2-methylbutyric acid (ΔTboil = 10°C, ΔpKa = 0.1), and 2) the bases diethyl methylamine and diisopropylether (ΔTboil = 3-6°C, ΔpKb ≈ 14). For both the acids and the bases the binary VLE-data and ternary data with solvents were measured using an ebulliometer. The solvents resulted in negative deviations of Raoult's law. The solvent selection was performed based on literature, followed by an experimental evaluation of the possible solvent types. For the valeric acid mixture the solvent 2-methylbutyrate, which is similar in structure to the components in the mixture, appeared to be most promising. In the ether-amine mixture a series of hydrogen bonding solvents with a hydroxyl group were found most promising, and also the regeneration of the solvent was an important factor in the study.</p

Partial stem resistance in Brassica napus to highly aggressive and genetically diverse Sclerotinia sclerotiorum isolates from Australia

Sclerotinia sclerotiorum is a fungal pathogen that causes stem rot in oilseed rape (Brassica napus). Previously, B. napus accessions with partial stem resistance to a Canadian S. sclerotiorum isolate (#321) were identified using a stem test in which flowering plants were inoculated with mycelium plugs. The present study examined the partial stem resistance of four of these accessions, PAK54, PAK93, DC21 and K22, following inoculation with Australian isolates. Mycelial compatibility groups and intergenic spacer (IGS) region haplotypes were identified among 71 isolates from Australian oilseed rape and lupin fields. Eleven genetically diverse isolates showed differences in aggressiveness when inoculated onto nine oilseed rape varieties and one Chinese accession. Isolates CU8.24, CU10.17 and CU11.19 were selected based on genetic diversity, growth rate in vitro and high aggressiveness in the initial screen and subsequently inoculated onto the four B. napus accessions. These accessions developed significantly smaller lesions compared with the susceptible control varieties (‘AV Garnet’ and ‘Westar’), with the average frequency of soft and collapsed lesions being less than 20% in PAK54, DC21 and K22, 29% in PAK93 and greater than 88% in the susceptible controls. Microscopic examination revealed that hyphae were typically confined to the stem cortex in the smallest lesions, but could be found in the stem pith in larger lesions. These results show that B. napus accessions PAK54, PAK93, DC21 and K22 can be used in Australia for development of varieties with partial stem resistance to S. sclerotiorum

Efficacy and safety of dupilumab in patients with severe chronic hand eczema with inadequate response or intolerance to alitretinoin:a randomized, double-blind, placebo-controlled phase IIb proof-of-concept study

BACKGROUND: Effective treatment options for patients with chronic hand eczema (CHE) are scarce. Dupilumab is licensed for the treatment of moderate-to-severe atopic dermatitis and has shown promising results on hand eczema in other studies.OBJECTIVE: To evaluate the efficacy and safety of dupilumab in adult patients with severe CHE (subtypes recurrent vesicular HE or chronic fissured HE) with an inadequate response/intolerance to alitretinoin, or when alitretinoin is medically inadvisable.METHODS: In this 16-weeks, randomized, double-blind, placebo-controlled, proof-of-concept phase IIb trial, patients with severe CHE were randomized 2:1 to dupilumab 300mg or placebo subcutaneously every two weeks. Patients visited the outpatient clinic at initiation of the study drug, and every 4 weeks until 16 weeks of treatment. The primary end point was the proportion of patients achieving at least 75% improvement on the Hand Eczema Severity Index score (HECSI-75) at week 16. Adverse events were monitored during each visit. The study was registered on ClinicalTrials.gov (identifier NCT04512339).RESULTS: In total, 30 patients were randomized, and 29 patients received the assigned study drug (dupilumab N = 20, placebo N = 9). At week 16, more patients achieved HECSI-75 in the dupilumab group than in the placebo group (95.0% [95% confidence interval (CI), 73.1%; 99.7.0%] versus 33.3% [95% CI, 9.0%; 69.1%]). Dupilumab also showed greater least square mean percentage change from baseline to week 16 in peak pruritus numerical rating scale than placebo (-66.5 ±10.7 [95% CI, -88.6; -44.5] versus -25.3 ±17.0 [95% CI, -60.1; 9.4]). Adverse events were similar between dupilumab and placebo groups and were mostly mild. There were no serious adverse events, nor did any of the adverse events lead to discontinuation of the study drug.CONCLUSION: Dupilumab was efficacious and well tolerated. Larger studies of longer duration, are needed to provide more evidence on the efficacy of dupilumab in CHE. Moreover, larger studies could also enable comparisons between clinical subtypes or etiological diagnoses.</p

Efficacy and safety of dupilumab in patients with severe chronic hand eczema with inadequate response or intolerance to alitretinoin:a randomized, double-blind, placebo-controlled phase IIb proof-of-concept study

BACKGROUND: Effective treatment options for patients with chronic hand eczema (CHE) are scarce. Dupilumab is licensed for the treatment of moderate-to-severe atopic dermatitis and has shown promising results on hand eczema in other studies.OBJECTIVE: To evaluate the efficacy and safety of dupilumab in adult patients with severe CHE (subtypes recurrent vesicular HE or chronic fissured HE) with an inadequate response/intolerance to alitretinoin, or when alitretinoin is medically inadvisable.METHODS: In this 16-weeks, randomized, double-blind, placebo-controlled, proof-of-concept phase IIb trial, patients with severe CHE were randomized 2:1 to dupilumab 300mg or placebo subcutaneously every two weeks. Patients visited the outpatient clinic at initiation of the study drug, and every 4 weeks until 16 weeks of treatment. The primary end point was the proportion of patients achieving at least 75% improvement on the Hand Eczema Severity Index score (HECSI-75) at week 16. Adverse events were monitored during each visit. The study was registered on ClinicalTrials.gov (identifier NCT04512339).RESULTS: In total, 30 patients were randomized, and 29 patients received the assigned study drug (dupilumab N = 20, placebo N = 9). At week 16, more patients achieved HECSI-75 in the dupilumab group than in the placebo group (95.0% [95% confidence interval (CI), 73.1%; 99.7.0%] versus 33.3% [95% CI, 9.0%; 69.1%]). Dupilumab also showed greater least square mean percentage change from baseline to week 16 in peak pruritus numerical rating scale than placebo (-66.5 ±10.7 [95% CI, -88.6; -44.5] versus -25.3 ±17.0 [95% CI, -60.1; 9.4]). Adverse events were similar between dupilumab and placebo groups and were mostly mild. There were no serious adverse events, nor did any of the adverse events lead to discontinuation of the study drug.CONCLUSION: Dupilumab was efficacious and well tolerated. Larger studies of longer duration, are needed to provide more evidence on the efficacy of dupilumab in CHE. Moreover, larger studies could also enable comparisons between clinical subtypes or etiological diagnoses.</p

Efficacy and safety of dupilumab in patients with severe chronic hand eczema with inadequate response or intolerance to alitretinoin:a randomized, double-blind, placebo-controlled phase IIb proof-of-concept study

BACKGROUND: Effective treatment options for patients with chronic hand eczema (CHE) are scarce. Dupilumab is licensed for the treatment of moderate-to-severe atopic dermatitis and has shown promising results on hand eczema in other studies.OBJECTIVE: To evaluate the efficacy and safety of dupilumab in adult patients with severe CHE (subtypes recurrent vesicular HE or chronic fissured HE) with an inadequate response/intolerance to alitretinoin, or when alitretinoin is medically inadvisable.METHODS: In this 16-weeks, randomized, double-blind, placebo-controlled, proof-of-concept phase IIb trial, patients with severe CHE were randomized 2:1 to dupilumab 300mg or placebo subcutaneously every two weeks. Patients visited the outpatient clinic at initiation of the study drug, and every 4 weeks until 16 weeks of treatment. The primary end point was the proportion of patients achieving at least 75% improvement on the Hand Eczema Severity Index score (HECSI-75) at week 16. Adverse events were monitored during each visit. The study was registered on ClinicalTrials.gov (identifier NCT04512339).RESULTS: In total, 30 patients were randomized, and 29 patients received the assigned study drug (dupilumab N = 20, placebo N = 9). At week 16, more patients achieved HECSI-75 in the dupilumab group than in the placebo group (95.0% [95% confidence interval (CI), 73.1%; 99.7.0%] versus 33.3% [95% CI, 9.0%; 69.1%]). Dupilumab also showed greater least square mean percentage change from baseline to week 16 in peak pruritus numerical rating scale than placebo (-66.5 ±10.7 [95% CI, -88.6; -44.5] versus -25.3 ±17.0 [95% CI, -60.1; 9.4]). Adverse events were similar between dupilumab and placebo groups and were mostly mild. There were no serious adverse events, nor did any of the adverse events lead to discontinuation of the study drug.CONCLUSION: Dupilumab was efficacious and well tolerated. Larger studies of longer duration, are needed to provide more evidence on the efficacy of dupilumab in CHE. Moreover, larger studies could also enable comparisons between clinical subtypes or etiological diagnoses.</p

Efficacy and safety of dupilumab in patients with severe chronic hand eczema with inadequate response or intolerance to alitretinoin:a randomized, double-blind, placebo-controlled phase IIb proof-of-concept study

BACKGROUND: Effective treatment options for patients with chronic hand eczema (CHE) are scarce. Dupilumab is licensed for the treatment of moderate-to-severe atopic dermatitis and has shown promising results on hand eczema in other studies.OBJECTIVE: To evaluate the efficacy and safety of dupilumab in adult patients with severe CHE (subtypes recurrent vesicular HE or chronic fissured HE) with an inadequate response/intolerance to alitretinoin, or when alitretinoin is medically inadvisable.METHODS: In this 16-weeks, randomized, double-blind, placebo-controlled, proof-of-concept phase IIb trial, patients with severe CHE were randomized 2:1 to dupilumab 300mg or placebo subcutaneously every two weeks. Patients visited the outpatient clinic at initiation of the study drug, and every 4 weeks until 16 weeks of treatment. The primary end point was the proportion of patients achieving at least 75% improvement on the Hand Eczema Severity Index score (HECSI-75) at week 16. Adverse events were monitored during each visit. The study was registered on ClinicalTrials.gov (identifier NCT04512339).RESULTS: In total, 30 patients were randomized, and 29 patients received the assigned study drug (dupilumab N = 20, placebo N = 9). At week 16, more patients achieved HECSI-75 in the dupilumab group than in the placebo group (95.0% [95% confidence interval (CI), 73.1%; 99.7.0%] versus 33.3% [95% CI, 9.0%; 69.1%]). Dupilumab also showed greater least square mean percentage change from baseline to week 16 in peak pruritus numerical rating scale than placebo (-66.5 ±10.7 [95% CI, -88.6; -44.5] versus -25.3 ±17.0 [95% CI, -60.1; 9.4]). Adverse events were similar between dupilumab and placebo groups and were mostly mild. There were no serious adverse events, nor did any of the adverse events lead to discontinuation of the study drug.CONCLUSION: Dupilumab was efficacious and well tolerated. Larger studies of longer duration, are needed to provide more evidence on the efficacy of dupilumab in CHE. Moreover, larger studies could also enable comparisons between clinical subtypes or etiological diagnoses.</p

Efficacy and safety of dupilumab in patients with severe chronic hand eczema with inadequate response or intolerance to alitretinoin:a randomized, double-blind, placebo-controlled phase IIb proof-of-concept study

BACKGROUND: Effective treatment options for patients with chronic hand eczema (CHE) are scarce. Dupilumab is licensed for the treatment of moderate-to-severe atopic dermatitis and has shown promising results on hand eczema in other studies.OBJECTIVE: To evaluate the efficacy and safety of dupilumab in adult patients with severe CHE (subtypes recurrent vesicular HE or chronic fissured HE) with an inadequate response/intolerance to alitretinoin, or when alitretinoin is medically inadvisable.METHODS: In this 16-weeks, randomized, double-blind, placebo-controlled, proof-of-concept phase IIb trial, patients with severe CHE were randomized 2:1 to dupilumab 300mg or placebo subcutaneously every two weeks. Patients visited the outpatient clinic at initiation of the study drug, and every 4 weeks until 16 weeks of treatment. The primary end point was the proportion of patients achieving at least 75% improvement on the Hand Eczema Severity Index score (HECSI-75) at week 16. Adverse events were monitored during each visit. The study was registered on ClinicalTrials.gov (identifier NCT04512339).RESULTS: In total, 30 patients were randomized, and 29 patients received the assigned study drug (dupilumab N = 20, placebo N = 9). At week 16, more patients achieved HECSI-75 in the dupilumab group than in the placebo group (95.0% [95% confidence interval (CI), 73.1%; 99.7.0%] versus 33.3% [95% CI, 9.0%; 69.1%]). Dupilumab also showed greater least square mean percentage change from baseline to week 16 in peak pruritus numerical rating scale than placebo (-66.5 ±10.7 [95% CI, -88.6; -44.5] versus -25.3 ±17.0 [95% CI, -60.1; 9.4]). Adverse events were similar between dupilumab and placebo groups and were mostly mild. There were no serious adverse events, nor did any of the adverse events lead to discontinuation of the study drug.CONCLUSION: Dupilumab was efficacious and well tolerated. Larger studies of longer duration, are needed to provide more evidence on the efficacy of dupilumab in CHE. Moreover, larger studies could also enable comparisons between clinical subtypes or etiological diagnoses.</p