Biological denitrification : fundamental kinetic studies, and process analysis for sequencing batch reactor operation

This study dealt with a detailed investigation of biological denitrification of nitrate and nitrite by a pure culture of Pseudomonas denitrificans (ATCC 13867), under anaerobic conditions. In the first part of the study, the kinetics of denitrification were studied in serum-bottle experiments. It was found that reduction of both nitrate and nitrite follows inhibitory expressions of the Andrews type. It was also found that when nitrite is present at levels above 15 mg/L, nitrite and nitrate are involved in a cross-inhibitory, non-competitive, interaction pattern. Analysis of the kinetic data has shown that the culture used has severe maintenance requirements, which can be described by the model proposed by Herbert. Experiments at different temperatures have revealed that the optimum temperature is around 38 °C. Activation energies have been determined as 8.6 Kcal/mole for nitrate, and 7.21 Kcal/mole for nitrite reduction. Studies on the effect of pH have shown that the optimal value is about 7.5. Based on the detailed kinetic expressions determined in the first part of the study, denitrification of nitrite and nitrate/nitrite mixtures was theoretically analyzed and experimentally investigated in a continuously operated sequencing batch reactor. The theoretical analysis was based on the bifurcation theory for forced systems. The different types of the dynamical behavior of the system were found, and are presented in the form of bifurcation diagrams and two-dimensional operating diagrams. The analysis predicts that there are domains in the operating parameter space where the system can reach different periodic patterns which are determined by the conditions under which the process is started-up. The analysis also predicts that improper selection of operating parameters can lead to high nitrite accumulation in the reactor. The predictions of the theory were tested in experiments with a specially designed system. The unit involved a fully automated 2-liter reactor which operated under different inlet flowrate and concentration conditions. During the experiments the system was perfectly sealed and the medium kept under a helium atmosphere of pressure slightly higher than 1 atm. In all cases, a remarkably good agreement was found between theoretical predictions and experimental data. The experimentally validated model can be used in process optimization studies, and preliminary scale-up calculations

Real-time photoacoustic flow cytography and photothermolysis of single circulating melanoma cells in vivo

Metastasis is responsible for as many as 90% of cancer-related deaths, and the deadliest skin cancer, melanoma, has a high propensity for metastasis. Since hematogenous spread of circulating tumor cells (CTCs) is cancer’s main route of metastasis, detecting and destroying CTCs can impede metastasis and improve patients’ prognoses. Extensive studies employing exogenous agents to detect tumor-specific biomarkers and guide therapeutics to CTCs have achieved promising results, but biosafety remains a critical concern. Taking another approach, physical detection and destruction of CTCs is a safer way to evaluate and reduce metastasis risks. Melanoma cells strongly express melanosomes, providing a striking absorption contrast with the blood background in the red to near-infrared spectrum. Exploiting this intrinsic optical absorption contrast of circulating melanoma cells, we coupled dual-wavelength photoacoustic flow cytography with a nanosecond-pulsed laser killing mechanism that specifically targets melanoma CTCs. We have successfully achieved in vivo label-free imaging of rare single CTCs and CTC clusters in mice. Further, the photoacoustic signal from a CTC immediately hardware-triggers a lethal pinpoint laser irradiation that lyses it on the spot in a thermally confined manner. Our technology can facilitate early inhibition of metastasis by clearing circulating tumor cells from vasculature

A water-immersible 2-axis scanning mirror microsystem for ultrasound and photoacoustic microscopic imaging applications

For both ultrasound and photoacoustic microscopic imaging, a fast scanning ability is required, whereas the liquid environment for acoustic propagation limits the usage of traditional MEMS scanning mirrors. In this paper, a new waterimmersible scanning mirror microsystem has been designed, fabricated and tested. To achieve reliable underwater scanning, flexible polymer torsion hinges fabricated by laser micromachining were used to support the reflective silicon mirror plate. Two efficient electromagnetic microactuators consisting of compact RF choke inductors and high-strength neodymium magnet disc were constructed to drive the silicon mirror plate around a fast axis and a slow axis, respectively. The performance of the water-immersible scanning mirror microsystem in both air and water were tested using the laser tracing method. For the fast axis, the resonance frequency reached 224 Hz in air and 164 Hz in water, respectively. The scanning angles in air and water under ±10 V AC driving (at the resonance frequencies) were ±13.6° and ±10°. The scanning angles in both air and water under ±16 V DC driving were ±12°. For the slow axis, the resonance frequency reached 55 Hz in air and 38 Hz in water, respectively. The scanning angles in air and water under ±10 V AC driving (at the resonance frequencies) were ±8.5° and ±6°. The scanning angles in both air and water under ±10 V DC driving were ± 6.5°. The feasibility of using such a water-immersible scanning mirror microsystem for scanning ultrasound microscopic (SAM) imaging has been demonstrated with a 25-MHz ultrasound pulse/echo system and a target consisting of three optical fibers

Associations of Long-Term Physical Activity Trajectories With All-Cause Mortality in a General Population

Objectives: We investigated the associations of mean levels of leisure-time physical activity (LTPA) and latent LTPA trajectories with all-cause mortality risk.Methods: Trajectories of LTPA were established using group-based trajectory analysis with a latent class growth model in a population-based cohort between 1996 and 2014. A Cox-proportional hazard model was conducted to examine the associations of LTPA quintiles and LTPA trajectories with all-cause mortality.Results: A total of 21,211 participants (age 18–90 years) were analyzed (median follow-up 16.8 years). The study participants were divided into five groups according to percentiles of LTPA (<20th, 20th–<40th, 40th–<60th, 60th–<80th, ≥80th) and LTPA trajectories (low/stable, medium/stable, increasing, decreasing, and fluctuating), respectively. Participants with a decreasing trajectory did not have a significantly lower risk of all-cause mortality despite having the highest baseline level of LTPA. In contrast, participants with a medium/stable (HR 0.84, 95% CI 0.72–0.98, p = 0.031) or an increasing (HR 0.57, 95% CI 0.33–0.97, p = 0.037) trajectory had a significantly lower risk of all-cause mortality.Conclusion: Promotion of maintaining stable LTPA is beneficial for public health and survival

Two separate gene clusters encode the biosynthetic pathway for the meroterpenoids, austinol and dehydroaustinol in Aspergillus nidulans

This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Journal of the American Chemical Society, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/ja209809t.Meroterpenoids are a class of fungal natural products that are produced from polyketide and terpenoid precursors. An understanding of meroterpenoid biosynthesis at the genetic level should facilitate engineering of second-generation molecules and increasing production of first-generation compounds. The filamentous fungus Aspergillus nidulans has previously been found to produce two meroterpenoids, austinol and dehydroaustinol. Using targeted deletions that we created, we have determined that, surprisingly, two separate gene clusters are required for meroterpenoid biosynthesis. One is a cluster of four genes including a polyketide synthase gene, ausA. The second is a cluster of ten additional genes including a prenyltransferase gene, ausN, located on a separate chromosome. Chemical analysis of mutant extracts enabled us to isolate 3,5-dimethylorsellinic acid and ten additional meroterpenoids that are either intermediates or shunt products from the biosynthetic pathway. Six of them were identified as novel meroterpenoids in this study. Our data, in aggregate, allow us to propose a complete biosynthetic pathway for the A. nidulans meroterpenoids

In vivo label-free photoacoustic flow cytography and on-the-spot laser killing of single circulating melanoma cells

Metastasis causes as many as 90% of cancer-related deaths, especially for the deadliest skin cancer, melanoma. Since hematogenous dissemination of circulating tumor cells is the major route of metastasis, detection and destruction of circulating tumor cells are vital for impeding metastasis and improving patient prognosis. Exploiting the exquisite intrinsic optical absorption contrast of circulating melanoma cells, we developed dual-wavelength photoacoustic flow cytography coupled with a nanosecond-pulsed melanoma-specific laser therapy mechanism. We have successfully achieved in vivo label-free imaging of rare single circulating melanoma cells in both arteries and veins of mice. Further, the photoacoustic signal from a circulating melanoma cell immediately hardware-triggers a lethal pinpoint laser irradiation to kill it on the spot in a thermally confined manner without causing collateral damage. A pseudo-therapy study including both in vivo and in vitro experiments demonstrated the performance and the potential clinical value of our method, which can facilitate early treatment of metastasis by clearing circulating tumor cells from vasculature

Publisher Correction: Copper adparticle enabled selective electrosynthesis of n-propanol.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Molecular genetic characterization of a cluster in A. terreus for biosynthesis of the meroterpenoid terretonin

Meroterpenoids are natural products produced from polyketide and terpenoid precursors. A gene targeting system for A. terreus NIH2624 was developed and a gene cluster for terretonin biosynthesis was characterized. The intermediates and shunt products were isolated from the mutant strains and a pathway for terretonin biosynthesis is proposed. Analysis of two meroterpenoid pathways corresponding to terretonin in A. terreus and austinol in A. nidulans reveals that they are closely related evolutionarily