A next generation, pilot-scale continuous sterilization system for fermentation media

A new continuous sterilization system was designed, constructed, started up, and qualified for media sterilization for secondary metabolite cultivations, bioconversions, and enzyme production. An existing Honeywell Total Distributed Control 3000-based control system was extended using redundant High performance Process Manager controllers for 98 I/O (input/output) points. This new equipment was retrofitted into an industrial research fermentation pilot plant, designed and constructed in the early 1980s. Design strategies of this new continuous sterilizer system and the expanded control system are described and compared with the literature (including dairy and bio-waste inactivation applications) and the weaknesses of the prior installation for expected effectiveness. In addition, the reasoning behind selection of some of these improved features has been incorporated. Examples of enhancements adopted include sanitary heat exchanger (HEX) design, incorporation of a “flash” cooling HEX, on-line calculation of F(o) and R(o), and use of field I/O modules located near the vessel to permit low-cost addition of new instrumentation. Sterilizer performance also was characterized over the expected range of operating conditions. Differences between design and observed temperature, pressure, and other profiles were quantified and investigated

iTRAQ Analysis of Complex Proteome Alterations in 3xTgAD Alzheimer's Mice: Understanding the Interface between Physiology and Disease

Alzheimer's disease (AD) is characterized by progressive cognitive impairment associated with accumulation of amyloid β-peptide, synaptic degeneration and the death of neurons in the hippocampus, and temporal, parietal and frontal lobes of the cerebral cortex. Analysis of postmortem brain tissue from AD patients can provide information on molecular alterations present at the end of the disease process, but cannot discriminate between changes that are specifically involved in AD versus those that are simply a consequence of neuronal degeneration. Animal models of AD provide the opportunity to elucidate the molecular changes that occur in brain cells as the disease process is initiated and progresses. To this end, we used the 3xTgAD mouse model of AD to gain insight into the complex alterations in proteins that occur in the hippocampus and cortex in AD. The 3xTgAD mice express mutant presenilin-1, amyloid precursor protein and tau, and exhibit AD-like amyloid and tau pathology in the hippocampus and cortex, and associated cognitive impairment. Using the iTRAQ stable-isotope-based quantitative proteomic technique, we performed an in-depth proteomic analysis of hippocampal and cortical tissue from 16 month old 3xTgAD and non-transgenic control mice. We found that the most important groups of significantly altered proteins included those involved in synaptic plasticity, neurite outgrowth and microtubule dynamics. Our findings have elucidated some of the complex proteome changes that occur in a mouse model of AD, which could potentially illuminate novel therapeutic avenues for the treatment of AD and other neurodegenerative disorders

A mobile phone application for the assessment and management of youth mental health problems in primary care: a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Over 75% of mental health problems begin in adolescence and primary care has been identified as the target setting for mental health intervention by the World Health Organisation. The <it>mobiletype </it>program is a mental health assessment and management mobile phone application which monitors mood, stress, coping strategies, activities, eating, sleeping, exercise patterns, and alcohol and cannabis use at least daily, and transmits this information to general practitioners (GPs) via a secure website in summary format for medical review.</p> <p>Methods</p> <p>We conducted a randomised controlled trial in primary care to examine the mental health benefits of the <it>mobiletype </it>program. Patients aged 14 to 24 years were recruited from rural and metropolitan general practices. GPs identified and referred eligible participants (those with mild or more mental health concerns) who were randomly assigned to either the intervention group (where mood, stress, and daily activities were monitored) or the attention comparison group (where only daily activities were monitored). Both groups self-monitored for 2 to 4 weeks and reviewed the monitoring data with their GP. GPs, participants, and researchers were blind to group allocation at randomisation. Participants completed pre-, post-, and 6-week post-test measures of the Depression, Anxiety, Stress Scale and an Emotional Self Awareness (ESA) Scale.</p> <p>Results</p> <p>Of the 163 participants assessed for eligibility, 118 were randomised and 114 participants were included in analyses (intervention group n = 68, comparison group n = 46). Mixed model analyses revealed a significant group by time interaction on ESA with a medium size of effect suggesting that the <it>mobiletype </it>program significantly increases ESA compared to an attention comparison. There was no significant group by time interaction for depression, anxiety, or stress, but a medium to large significant main effect for time for each of these mental health measures. Post-hoc analyses suggested that participation in the RCT lead to enhanced GP mental health care at pre-test and improved mental health outcomes.</p> <p>Conclusions</p> <p>Monitoring mental health symptoms appears to increase ESA and implementing a mental health program in primary care and providing frequent reminders, clinical resources, and support to GPs substantially improved mental health outcomes for the sample as a whole.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00794222">NCT00794222</a>.</p

Long memory estimation for complex-valued time series

Long memory has been observed for time series across a multitude of fields and the accurate estimation of such dependence, e.g. via the Hurst exponent, is crucial for the modelling and prediction of many dynamic systems of interest. Many physical processes (such as wind data), are more naturally expressed as a complex-valued time series to represent magnitude and phase information (wind speed and direction). With data collection ubiquitously unreliable, irregular sampling or missingness is also commonplace and can cause bias in a range of analysis tasks, including Hurst estimation. This article proposes a new Hurst exponent estimation technique for complex-valued persistent data sampled with potential irregularity. Our approach is justified through establishing attractive theoretical properties of a new complex-valued wavelet lifting transform, also introduced in this paper. We demonstrate the accuracy of the proposed estimation method through simulations across a range of sampling scenarios and complex- and real-valued persistent processes. For wind data, our method highlights that inclusion of the intrinsic correlations between the real and imaginary data, inherent in our complex-valued approach, can produce different persistence estimates than when using real-valued analysis. Such analysis could then support alternative modelling or policy decisions compared with conclusions based on real-valued estimation

Characterization of interactions between transcription factors and a regulatory region spanning nt-320 to-281 of the HIV-1 LTR in T-lymphoid and non-T-lymphoid cells

HIV-1 gene expression is regulated by the interplay of transcription factors with multiple binding motifs present within the U3, R and U5 regions of the long terminal repeat (LTR). Here we report novel DNA binding complexes (termed 9a, 9b and 9c) between nuclear proteins from T-lymphoid and non-T-lymphoid cells and a region of the U3 LTR between nucleotides (nts) -320 to -281 in the HIV strain HXB2. Complex 9b bound a motif predicted to bind E-box or c-Myb proteins and a partially overlapping dyad symmetrical motif, and included basic helix-loop-helix proteins (E12, E47 or ITF-1) but surprisingly not c-Myb. Complex 9c, which bound to a pair of GATA sites, included GATA-3 and GATA-4 in Jurkat and MT-2 cells, respectively. We also demonstrate that the c-Myb/E-box and GATA sites form a bipartite motif required for the formation of complex 9a. Transient transfection experiments with T cells revealed that in the context of a minichromosome assembled full-length LTR, mutation of region -320 to -281 increased basal and PMA-stimulated LTR activity. These findings suggest that this region is an important component of the HIV-1 LTR required for response to different cellular transcription factors. Copyright (C) 2002 National Science Council, ROC and S. Karger AG, Basel