In this work we investigated the fluid dynamics in a pilot-scale bubble column equipped with an asymmetric “tree” type sparger at superficial velocities between 0.01 and 0.37 m s–1. We present an ...extensive experimental data set consisting of overall holdup measurements, liquid velocity, gas velocity, and local gas volume fraction profiles as well as bubble size distributions. The second part of this work examines the modeling of the column using computational fluid dynamics (CFD). It is found that the computationally efficient single bubble size model used in this work offered satisfactory predictions of the complex flow patterns found inside bubble columns operated in the industrially relevant heterogeneous flow regime.
In this work we have quantified the effect of surfactant addition on the overall hold-up, local hold-up, liquid velocity, gas velocity, bubble size distribution (BSD) and mixing time using a bubble ...column 0.39m in diameter and 2m in height operated at superficial velocities between 0.01 and 0.28m/s. The surfactant used was 2-propanol, which was chosen because its addition causes an air/water system to behave similarly to the complex and poorly defined fermentation media used in industrial bioprocesses. The second portion of the study examines the extension of an existing computational fluid dynamics (CFD) model to account for the impact of surfactant addition; it was found that the inclusion of a correction term into the drag coefficient calculation led to predictions that were in good agreement with experimental results.
•Impact of surfactant addition on pilot-scale bubble column was quantified.•Measurements of mixing, BSD, hold-up, liquid and gas velocity made.•CFD model of surfactant containing systems developed.•Model in good agreement with experimental data.
Meticillin-resistant Staphylococcus pseudintermedius (MRSP) has recently emerged as a worldwide cause of canine pyoderma. In this study, we characterized 22 S. pseudintermedius isolates cultured from ...19 dogs with pyoderma that attended a veterinary dermatology referral clinic in Australia in 2011 and 2012. Twelve isolates were identified as MRSP by mecA real-time PCR and phenotypic resistance to oxacillin. In addition to β-lactam resistance, MRSP isolates were resistant to erythromycin (91.6 %), gentamicin (83.3 %), ciprofloxacin (83.3 %), chloramphenicol (75 %), clindamycin (66 %), oxytetracycline (66 %) and tetracycline (50 %), as shown by disc-diffusion susceptibility testing. Meticillin-susceptible S. pseudintermedius isolates only showed resistance to penicillin/ampicillin (90 %) and tetracycline (10 %). PFGE using the SmaI restriction enzyme was unable to type nine of the 12 MRSP isolates. However the nine isolates provided the same PFGE pulsotype using the Cfr91 restriction enzyme. Application of the mec-associated direct repeat unit (dru) typing method identified the nine SmaI PFGE-untypable isolates as dt11cb, a dru type that has only previously been associated with MRSP sequence type (ST)45 isolates that possess a unique SCCmec element. The dt11cb isolates shared a similar multidrug-resistant antibiogram phenotype profile, whereas the other MRSP isolates, dt11a, dt11af (dt11a-associated) and dt10h, were resistant to fewer antibiotic classes and had distinct PFGE profiles. This is the first report of MRSP causing pyoderma in dogs from Australia. The rapid intercontinental emergence and spread of multidrug-resistant MRSP strains confirms the urgent need for new treatment modalities for recurrent canine pyoderma in veterinary practice.
Helicases, G4-DNAs, and drug design Hale, Tracy K; Norris, Gillian E; Jameson, Geoffrey B ...
ChemMedChem,
September 2014, Letnik:
9, Številka:
9
Journal Article
Recenzirano
New helicase assays that recognise therapeutically important G4-DNA structures will lead to the discovery of novel molecular entities that bind not only to G4-tetrads, but also to grooves and loops ...of G4-DNA. Such assays can also provide inhibitors of G4-specific helicases that will shed light on the emerging involvement of helicases in cancer and other diseases linked to defective DNA repair pathways.
•Staphylococcus felis isolates were examined using whole genome sequencing and phenotypic tests.•Gene sequences of putative virulence factors were found in all isolates.•Ninety two percent of ...isolates were susceptible to all antimicrobials tested.•One isolate caused coagulation of feline plasma.
This study used phenotypic tests and whole genome sequencing to characterise a collection of 37 clinical Staphylococcus felis isolates from cats. Samples were isolated from a range of diseases including feline lower urinary tract disease (n = 15), otitis externa (n = 13), and ocular disease (n = 2). Isolates were identified using MALDI-TOF MS and by BLASTn analysis of S. felis-specific 16S rRNA, rpoB and nuc genes in whole genome sequence-based contigs. Phenotypic antimicrobial resistance was determined using disk diffusion and broth microdilution. Coagulase activity was assessed using feline and rabbit plasma. Genomes were screened for putative virulence and antimicrobial resistance genes using the sequences of known genes from other staphylococci as homologous references. Phylogenetic relationships were inferred using single nucleotide polymorphisms. One isolate was coagulase-positive when tested with feline plasma but all isolates were rabbit plasma coagulase-negative. No genetic determinant of coagulase activity was identified in this isolate. A range of putative virulence genes were found amongst isolates including genes associated with adhesion, toxin production and immune evasion. Ninety two percent of isolates were fully susceptible to all antimicrobials tested, which was reflected by a general absence of resistance genes. Clustering within the phylogenetic tree suggested a multiclonal population structure; this clustering did not correlate with disease syndrome or geographic origin of the isolate. Future studies of veterinary staphylococci will benefit from the publicly available S. felis draft genomes that were generated in this study.
•Ultra-high resolution crystal structure of caprine βlg.•AUC and SAXS data confirm that caprine βlg is a dimer in solution.•AUC data (between 5 and 50μM) suggest that the protein is in a ...monomer–dimer self-association.
β-Lactoglobulin (βlg) is the most abundant whey protein in the milks of ruminant animals. While bovine βlg has been subjected to a vast array of studies, little is known about the caprine ortholog. We present an ultra-high resolution crystal structure of caprine βlg complemented by analytical ultracentrifugation and small-angle X-ray scattering data. In both solution and crystalline states caprine βlg is dimeric (KD<5μM); however, our data suggest a flexible quaternary arrangement of subunits within the dimer. These structural findings will provide insight into relationships among structural, processing, nutritional and immunological characteristics that distinguish cow’s and goat’s milk.
cBlg and cBlgbind by cosedimentation in solution (View interaction)
bBlg and bBlgbind by cosedimentation in solution (View interaction)
cBlg and cBlgbind by X ray scattering (View interaction)
cBlg and cBlgbind by X-ray crystallography (View interaction)
Several studies suggest that maternal folic acid supplementation before or during pregnancy protects against childhood acute lymphoblastic leukemia (ALL). We investigated associations between ALL ...risk and folate pathway gene polymorphisms, and their modification by maternal folic acid supplements, in a population-based case-control study (2003-2007).
All Australian pediatric oncology centers provided cases; controls were recruited by national random digit dialing. Data from 392 cases and 535 controls were included. Seven folate pathway gene polymorphisms (MTHFR 677C>T, MTHFR 1298A>C, MTRR 66A>G, MTR 2756 A>G, MTR 5049 C>A, CBS 844 Ins68, and CBS 2199 T>C) were genotyped in children and their parents. Information on prepregnancy maternal folic acid supplement use was collected. ORs were estimated with unconditional logistic regression adjusted for frequency-matched variables and potential confounders. Case-parent trios were also analyzed.
There was some evidence of a reduced risk of ALL among children who had, or whose father had, the MTRR 66GG genotype: ORs 0.60 95% confidence interval (CI) 0.39-0.91 and 0.64 (95% CI, 0.40-1.03), respectively. The ORs for paternal MTHFR 677CT and TT genotypes were 1.41 (95% CI, 1.02-1.93) and 1.81 (95% CI, 1.06-3.07). ORs varied little by maternal folic acid supplementation.
Some folate pathway gene polymorphisms in the child or a parent may influence ALL risk. While biologically plausible, underlying mechanisms for these associations need further elucidation.
Folate pathway polymorphisms may be related to risk of childhood ALL, but larger studies are needed for conclusive results.
Background. Improved treatment options are needed for patients infected with multidrug-resistant human immunodeficiency virus type 1 (HIV-1). The nonpeptidic protease inhibitor tipranavir has ...demonstrated antiviral activity against many protease inhibitor-resistant HIV-1 isolates. The Randomized Evaluation of Strategic Intervention in multi-drug reSistant patients with Tipranavir (RESIST-1) trial is an ongoing, open-label study comparing the efficacy and safety of ritonavir-boosted tipranavir (TPV/r) with an investigator-selected ritonavir-boosted comparator protease inhibitor (CPI/r) in treatment-experienced, HIV-1-infected patients. Methods. Six hundred twenty antiretroviral-experienced patients were treated at 125 sites in North America and Australia. Before randomization, all patients underwent genotypic resistance testing, which investigators used to select a CPI/r and an optimized background regimen. Patients were randomized to receive TPV/r or CPI/r and were stratified on the basis of preselected protease inhibitor and enfuvirtide use. Treatment response was defined as a confirmed reduction in the HIV-1 load of ⩾1 log10 less than the baseline level without treatment change at week 24. Results. Mean baseline HIV-1 loads and CD4+ cell counts were 4.74 log10 copies/mL and 164 cells/mm3, respectively. At week 24, a total of 41.5% of patients in the TPV/r arm and 22.3% in the CPI/r arm had a ⩾1-log10 reduction in the HIV-1 load (intent-to-treat population; P < .0001). Mean increases in the CD4+ cell count of 54 and 24 cells/mm3 occurred in the TPV/r and CPI/r groups, respectively. Adverse events were slightly more common in the TPV/r group and included diarrhea, nausea, and vomiting. Elevations in alanine and aspartate aminotransferase levels and in cholesterol/triglyceride levels were more frequent in the TPV/r group. Conclusions. TPV/r demonstrated superior antiviral activity, compared with investigator-selected, ritonavir-boosted protease inhibitors, at week 24 in treatment-experienced patients with multidrug-resistant HIV-1 infection.
We examined the oxacillin resistance phenotype and genomic structure of staphylococcal cassette chromosome
(SCC
) elements from 77 veterinary methicillin-resistant
(MRSP) isolates. Isolates were ...characterized by oxacillin broth microdilution, whole-genome sequencing, and bioformatics analysis. Five previously described SCC
elements, and a sixth novel element, were identified: SCC
III (also known as II-III), ΨSCC
, and SCC
(a SCC
VII variant), all previously described in MRSP, and SCC
IVg and SCC
V
, previously described in both methicillin-resistant
(MRSA) and MRSP. The sixth element was novel and found among nine geographically clustered isolates. This novel pseudostaphylococcal cassette chromosome (ΨSCC
) contained a class A
gene complex but lacked
genes. It also harbored heavy metal (cadmium) resistance determinants. The median oxacillin MIC values among ΨSCC
, SCC
III, and SCC
V
isolates were significantly higher than those determined for the SCC
VII variant isolates and ΨSCC
and SCC
IVg isolates. ΨSCC
was found exclusively in sequence type 497 (ST497), an MRSP clone that is locally successful in Victoria, Australia. Future studies are necessary to determine if this clone has disseminated further afield and if ΨSCC
has moved into other MRSP lineages or staphylococcal species.
is a significant veterinary pathogen and occasional cause of infections in humans. β-Lactams are an important group of antimicrobials used to treat staphylococcal infections in humans and animals. However, when staphylococci become methicillin resistant via the acquisition of a mobile genetic element called staphylococcal cassette chromosome
(SCC
), they become resistant to all β-lactams. This study detected a novel SCC
element among a cluster of methicillin-resistant
isolates from animals in Australia. It also detected SCC
elements in
that had high similarity to those identified in methicillin-resistant
, demonstrating how human and animal pathogens can share the same resistance determinants.
Abstract only
226
Background: Based on the positive results of the CALGB 80803 study (J Clin Oncol 2017;35:1 abstr), we have added D to induction FOLFOX and pre-op CRT. Methods: Patients (Pts) had T
...any
N+ or T3-4N
any
M0 esophageal and Siewert Type I-III GEJ adenocarcinoma staged by EUS, PET/CT and CT. Pts received mFOLFOX6 ×2 prior to repeat PET/CT. PET responders (PETr) received 5-FU or capecitabine and oxaliplatin with RT to 50.4Gy, while induction PET non-responders (PETnr) received carboplatin/paclitaxel with RT. All Pts received D 1,500 mg q4W ×2 starting 2 wks prior to and during CRT. Esophagectomy was planned 6-8 weeks after CRT. Pts who had R0 resections received adjuvant D 1,500mg q4W ×6. Results: 36 Pts have been enrolled: 25 GEJ, 11 esophageal; 23 N+ and 32 T3/4. 26 of 36 Pts (72%) are PETr. 2 Pts developed metastatic disease after CRT and 9 Pts remain on preop treatment. 25 Pts have had surgery (Table). Pathologic complete response (pCR) was seen in 6 (24%); 5 Pts (20%) had ypT1N0 tumors with 99% response and 2 Pts (8%) had ypT0N1 with 99% response. 20 Pts (80%) had >90% response. 3 Pts had MSI tumors (2 PETr; 1 pCR, 1 T1aN0 99% response, 1 ypT2N0 90% response). Notable grade (gd) 3/4 adverse events (AEs) observed were neutropenia in 8 Pts (22%), diarrhea and vomiting in 2 Pts each (6%). Notable gd 1/2 AEs in ≥20%: anemia (31 Pts), thrombocytopenia (29 Pts), nausea (21 Pts), fatigue (25 Pts), increased AST (20 Pts), constipation and diarrhea (9 Pts), diarrhea (8 Pts). Immune-related AEs noted were gd 2 dermatitis (2 Pts), gd 3 hepatitis and gd 1 hypothyroidism in 1 Pt each. Median length of post-op stay was 8 days, with 12% anastomotic complication rate, including 1 Pt who died of hematemesis 16 days after discharge from 55-day hospitalization. Conclusions: The addition of D to induction FOLFOX and PET-directed CRT is safe and feasible. pCR and near-pCR in ½ of operated Pts is encouraging and compares favorably to the pCR rate of 31% in CALGB 80803 Pts who received induction FOLFOX. The final pCR rate and correlatives for the fully accrued study will be presented. Clinical trial information: NCT02962063. Table: see text
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