UNDERSTANDING EFFECT OF IONIC LIQUID ON METALLOPROTEINS: LACCASE AND AZURIN

Interactions between ionic liquids and biomolecules have been of great interest due to the intrinsic properties of ionic liquids and the flexibility to mix and match cations and anions to create unique ionic liquids. A number of ionic liquid-biomolecule studies have focused on the interactions with proteins, including industrially relevant enzymes. One of these, laccase from Trametes versicolor, is a naturally derived enzyme used in the breakdown of phenolic compounds in a wide variety of industries, especially useful in breakdown of lignocellulosic materials. Here, a combination of experiments and molecular dynamics (MD) simulations were used to investigate the interactions of ionic liquids with laccase. Enzyme kinetics assays indicated that ionic liquids composed of tetramethylguanidine (TMG) and either serine or threonine caused significant reduction of enzymatic activity, while kinetics was not impacted by TMG-Asp or TMG-Glu ionic liquids. Similarly, intrinsic fluorescence of laccase in the presence of TMG-Ser and TMG-Thr exhibited a shift in spectral properties consistent with structural destabilization, but again TMG-Asp and TMG-Glu had no impact. MD simulations of laccase and ABTS with/without TMG-Ser ionic liquid provide insight into the deactivation mechanism of laccase. The simulations indicate that TMG-Ser disrupts the electron transfer mechanism in laccase

Peri-prostatic fat volume measurement as a predictive tool for castration resistance in advanced prostate cancer

Background: Obesity and aggressive prostate cancer (PC) may be linked, but how local peri-prostatic fat relates to tumour response following androgen deprivation therapy (ADT) is unknown. Objective: To test if peri-prostatic fat volume (PPFV) predicts tumour response to ADT. Design, setting, and participants: We performed a retrospective study on consecutive patients receiving primary ADT. From staging pelvic magnetic resonance imaging scans, the PPFV was quantified with OsirixX 6.5 imaging software. Statistical (univariate and multivariate) analysis were performed using R Version 3.2.1. Results and limitations: Of 224 consecutive patients, 61 with advanced (≥T3 or N1 or M1) disease had (3-mm high resolution axial sections) pelvic magnetic resonance imaging scan before ADT. Median age = 75 yr; median PPFV = 24.8 cm3 (range, 7.4–139.4 cm3). PPFV was significantly higher in patients who developed castration resistant prostate cancer (CRPC; n = 31), with a median of 37.9 cm3 compared with 16.1 cm3 (p < 0.0001, Wilcoxon rank sum test) in patients who showed sustained response to ADT (n = 30). Multivariate analysis using Cox proportional hazards models were performed controlling for known predictors of CRPC. PPFV was shown to be independent of all included factors, and the most significant predictor of time to CRPC. Using our multivariate model consisting of all known factors prior to ADT, PPFV significantly improved the area under the curve of the multivariate models receiver operating characteristic analysis. The main study limitation is a relatively small cohort to account for multiple variables, necessitating a future large-scale prospective analysis of PPFV in advanced PC. Conclusions: PPFV quantification in patients with advanced PC predicts tumour response to ADT

Acute puerperal uterine inversion: Case report

Acute puerperal uterine inversion is a rare but potentially fatal obstetric emergency in which the uterine fundus collapses into the uterine cavity. Maternal mortality is high unless the condition is recognised and quickly corrected. The duration of time elapsed from moment of diagnosis to that of correction, along with rapid resuscitation measures are of utmost importance in its prognosis. A recent case managed successfully is described followed by a short review of the literature

A systematic review of the role of bisphosphonates in metastatic disease

Objectives: To identify evidence for the role of bisphosphonates in malignancy for the treatment of hypercalcaemia, prevention of skeletal morbidity and use in the adjuvant setting. To perform an economic review of current literature and model the cost effectiveness of bisphosphonates in the treatment of hypercalcaemia and prevention of skeletal morbidity Data sources: Electronic databases (1966-June 2001). Cochrane register. Pharmaceutical companies. Experts in the field. Handsearching of abstracts and leading oncology journals (1999-2001). Review methods: Two independent reviewers assessed studies for inclusion, according to predetermined criteria, and extracted relevant data. Overall event rates were pooled in a meta-analysis, odds ratios ( OR) were given with 95% confidence intervals (CI). Where data could not be combined, studies were reported individually and proportions compared using chi- squared analysis. Cost and cost-effectiveness were assessed by a decision analytic model comparing different bisphosphonate regimens for the treatment of hypercalcaemia; Markov models were employed to evaluate the use of bisphosphonates to prevent skeletal-related events (SRE) in patients with breast cancer and multiple myeloma. Results: For acute hypercalcaemia of malignancy, bisphosphonates normalised serum calcium in >70% of patients within 2-6 days. Pamidronate was more effective than control, etidronate, mithramycin and low-dose clodronate, but equal to high dose clodronate, in achieving normocalcaemia. Pamidronate prolongs ( doubles) the median time to relapse compared with clodronate or etidronate. For prevention of skeletal morbidity, bisphosphonates compared with placebo, significantly reduced the OR for fractures (OR [95% CI], vertebral, 0.69 [0.57-0.84], non-vertebral, 0.65 [0.54-0.79], combined, 0.65 [0.55-0.78]) radiotherapy 0.67 [0.57-0.79] and hypercalcaemia 0.54 [0.36-0.81] but not orthopaedic surgery 0.70 [0.46-1.05] or spinal cord compression 0.71 [0.47-1.08]. However, reduction in orthopaedic surgery was significant in studies that lasted over a year 0.59 [0.39-0.88]. Bisphosphonates significantly increased the time to first SRE but did not affect survival. Subanalyses were performed for disease groups, drugs and route of administration. Most evidence supports the use of intravenous aminobisphosphonates. For adjuvant use of bisphosphonates, Clodronate, given to patients with primary operable breast cancer and no metastatic disease, significantly reduced the number of patients developing bone metastases. This benefit was not maintained once regular administration had been discontinued. Two trials reported significant survival advantages in the treated groups. Bisphosphonates reduce the number of bone metastases in patients with both early and advanced breast cancer. Bisphosphonates are well tolerated with a low incidence of side-effects. Economic modelling showed that for acute hypercalcaemia, drugs with the longest cumulative duration of normocalcaemia were most cost-effective. Zoledronate 4 mg was the most costly, but most cost-effective treatment. For skeletal morbidity, Markov models estimated that the overall cost of bisphosphonate therapy to prevent an SRE was pound250 and pound1500 per event for patients with breast cancer and multiple myeloma, respectively. Bisphosphonate treatment is sometimes cost-saving in breast cancer patients where fractures are prevented. Conclusions: High dose aminobisphosphonates are most effective for the treatment of acute hypercalcaemia and delay time to relapse. Bisphosphonates significantly reduce SREs and delay the time to first SRE in patients with bony metastatic disease but do not affect survival. Benefit is demonstrated after administration for at least 6-12 months. The greatest body of evidence supports the use of intravenous aminobisphosphonates. Further evidence is required to support use in the adjuvant setting

Enhancement of quantum dot peak-spacing fluctuations in the fractional q uantum Hall regime

The fluctuations in the spacing of the tunneling resonances through a quantum dot have been studied in the quantum Hall regime. Using the fact that the ground-state of the system is described very well by the Laughlin wavefunction, we were able to determine accurately, via classical Monte Carlo calculations, the amplitude and distribution of the peak-spacing fluctuations. Our results clearly demonstrate a big enhancement of the fluctuations as the importance of the electronic correlations increases, namely as the density decreases and filling factor becomes smaller. We also find that the distribution of the fluctuations approaches a Gaussian with increasing density of random potentials.Comment: 6 pages, 3 figures all in gzipped tarred fil

Signatures of Inelastic Scattering in Coulomb-Blockade Quantum Dots

We calculate the finite-temperature conductance peak-height distributions in Coublomb-blockade quantum dots in the limit where the inelastic scattering rate in the dot is large compared with the mean elastic tunneling rate. The relative reduction of the standard deviation of the peak-height distribution by a time-reversal symmetry-breaking magnetic field, which is essentially temperature-independent in the elastic limit, is enhanced by the inclusion of inelastic scattering at finite temperature. We suggest this quantity as an independent experimental probe for inelastic scattering in closed dots.Comment: 4 pages, 3 eps figures, revtex

Parametrical modeling and design optimization of blood plasma separation device with microchannel mechanism

This paper presents an analysis of biofluid behavior in a T-shaped microchannel device and a design optimization for improved biofluid performance in terms of particle liquid separation. The biofluid is modeled with single phase shear rate non-Newtonian flow with blood property. The separation of red blood cell from plasma is evident based on biofluid distribution in the microchannels against various relevant effects and findings, including Zweifach-Fung bifurcation law, Fahraeus effect, Fahraeus-Lindqvist effect and cell free phenomenon. The modeling with the initial device shows that this T-microchannel device can separate red blood cell from plasma but the separation efficiency among different bifurcations varies largely. In accordance with the imbalanced performance, a design optimization is conducted. This includes implementing a series of simulations to investigate the effect of the lengths of the main and branch channels to biofluid behavior and searching an improved design with optimal separation performance. It is found that changing relative lengths of branch channels is effective to both uniformity of flow rate ratio among bifurcations and reduction of difference of the flow velocities between the branch channels, whereas extending the length of the main channel from bifurcation region is only effective for uniformity of flow rate ratio

Redefining Career Communities in Higher Education

This study aims to revisit the understudied concept of career communities. Using mixed methods, this study assesses how university students define and characterize career communities compared to general communities. Based on our interviews (N=25) and survey (N=123), we formally define a career community more narrowly as a group of individuals who share similar career interests or aspirations where one can receive direct or indirect customized benefits through the exchange of knowledge, expertise, and resources. Theoretical and practical implications with future research opportunities have been recommended