RF Electronics: design and simulation

[Extract] The material presented in this book evolved from teaching analogue electronics courses at James Cook University over many years. When I started teaching electronics design, computer simulation tools were non-existent and most of the design optimisation was done by replacing components in hardware. It was a big step forward when EESOF became available in the mid 1980's. The computer simulation tools have progressed enormously since then. Early in my career, I was given the following advice for designing electronic circuits. "Get the circuit to work and then start taking components out. Put back the one that stops the circuit from working." This is a silly statement, since in a proper design removing any component will stop if from working, but it does illustrate the goal of any designer: Design a circuit that will work first time, according to specification. It must do so reliably and at as low a cost as possible. Since labour is expensive, the circuits also should not require any adjustments after manufacture in order that they meet the specifications

High-efficiency biolistic co-transformation and regeneration of 'Chardonnay' ( Vitis vinifera L.) containing npt-II and antimicrobial peptide genes

A reliable and efficient system for transformation and regeneration of 'Chardonnay' (Vitis vinifera L.) plants via microprojectile bombardment was developed. Improvements over the previous biolistic transformation system included: (1) the use of gold particles for bombardment; (2) step-wise selection at 10 then 15mg/l kanamycin; and (3) embryo induction at 27°C. Embryogenic cell cultures were either bombarded with pBI426, which contains the reporter gene gus (uidA) coding for β-glucuronidase (GUS), or were co-bombarded with pSAN237 carrying the npt-II (neomycin phosphotransferase II) selectable marker gene, and a second plasmid with an antimicrobial peptide gene. A large number of transient (7,883±1,928) and stable (46±32) blue spots per plate at 2 and 95days after bombardment, respectively, were obtained according to GUS expression analyses. A total of 447 putative transgenic embryos was harvested from 84 bombarded plates. From these embryos, 242 (54%) were regenerated into plants within the first year of the experiment. Southern blot analyses confirmed integration of the transgenes into the grape genome. Co-transformation was tested with four separate antimicrobial constructs. The co-transformation frequency of unlinked genes was 48% as measured by polymerase chain reaction (PCR), and 56% as estimated by dot blot hybridization. Expression of the gus gene, and PCR and Southern blot analyses of npt-II and antimicrobial genes from regenerated plants document stable transformation of 'Chardonnay' and establish the parameters for highly-efficient biolistic transformation in V. vinifer

Viral deubiquitinating proteases and the promising strategies of their inhibition

Several viruses are now known to code for deubiquitinating proteases in their genomes. Ubiquitination is an essential post-translational modification of cellular substrates involved in many processes in the cell, including in innate immune signalling. This post-translational modification is regulated by the ubiquitin conjugation machinery, as well as various host deubiquitinating enzymes. The conjugation of ubiquitin chains to several innate immune related factors is often needed to induce downstream signalling, shaping the antiviral response. Viral deubiquitinating proteins, besides often having a primary function in the viral replication cycle by cleaving the viral polyprotein, are also able to cleave ubiquitin chains from such host substrates, in that way exerting a function in innate immune evasion. The presence of viral deubiquitinating enzymes has been firmly established for numerous animal-infecting viruses, such as some well-researched and clinically important nidoviruses, and their presence has now been confirmed in several plant viruses as well. Viral proteases in general have long been highlighted as promising drug targets, with a current focus on small molecule inhibitors. In this review, we will discuss the range of viral deubiquitinating proteases known to date, summarise the various avenues explored to inhibit such proteases and discuss novel strategies and models intended to inhibit and study these specific viral enzymes.</p

The burden of disease in patients eligible for mentalization-based treatment (MBT): Quality of life and costs

Background: Mentalization-Based Treatment (MBT) is a promising, though expensive treatment for severely ill patients with Borderline Personality Disorder (BPD). A high burden of disease in terms of quality of life (QoL) and life years lost can be a reason to prioritize mental health interventions, and specifically for BPD patients. Moreover, when the societal costs of the illness are high, spending resources on high treatment costs would be more easily legitimized. Therefore, the purpose of this study was to calculate the burden of disease of BPD patients eligible for MBT. Methods: The 403 patients included in this study were recruited from two mental health care institutes in the Netherlands. All patients were eligible for MBT. Burden of disease consisted of QoL, measured with the EuroQol EQ-5D-3L, and costs, calculated using the Trimbos and Institute for Medical Technology Assessment Questionnaire for Costs Associated with Psychiatric Illness. Results: The mean QoL index score was.48. The mean total costs in the year prior to treatment were €16,879 per patient, of which 21 % consisted of productivity costs. Conclusions: The burden of disease in BPD patients eligible for MBT is high, which makes it more likely that society is willing to invest in treatment for these patients. However, this finding should not be interpreted as a license to unlimitedly use resources to reimburse treatment for severe BPD patients, as these findings do not provide any information on the effectiveness of MBT or other available treatment programs for BPD. The effectiveness of available treatments should be evident by studies on the effectiveness of the treatment itself and by comparing the effectiveness of these treatments to treatment as usual and to other treatment options for BPD patients. Trial registration: The data on this paper came from two trials: NTR2175and NTR2292

Growth Manipulation of Slicer Carrots by Foliar-applied Gibberellic Acid in New York

New York, USA, is a regional hub for processing carrot (Daucus carota ssp. sativus) production and Nantes-type cultivars are preferred for slicing. Diameter is critical in carrots for slicing, with roots larger than 1 5/8 inch being rejected. The potential to manipulate carrot root diameter and hence suitability for slicing by foliar-applied gibberellic acid (GA3) was tested in four small plot replicated field trials over 3 years (2020, 2021, and 2022). In the most efficacious treatments, GA3 resulted in a 23.1% to 135.4% increase in foliar biomass at the expense of root weight and diameter. Increases in foliar biomass are beneficial to facilitate top-pulling harvest. Reductions in root diameter from GA3 ranged from 9.5% to 19.6%, and in 2020 and 2022, increased the proportion of roots suitable for slicing. GA3 did not significantly affect root length and number. In two 2021 trials, GA3 increased color intensity quantified by a colorimeter, but this change was not noticeable to the naked eye. The optimal number of GA3 applications was seasonally dependent, ranging from a single application at 107 to 108 days after planting (DAP) in 2021, to two applications at 74 + 92 DAP in 2022. Three GA3 applications per season or late applications (up to 14 days prior to harvest) were not beneficial

Medication strategies in first episode psychosis patients:A survey among psychiatrists

Aim There is an ongoing debate regarding the optimal timing of discontinuation of antipsychotic drugs for patients with first episode psychosis. Although most guidelines recommend maintenance therapy for at least 1 or 2 years after reaching remission, study results indicate that early discontinuation may be beneficial for at least a subsample of patients. To date, little is known about which medication strategies are applied in patients recovering from a first psychotic episode. In this study, we examined the beliefs and practices of clinicians on medication discontinuation. Methods We performed a survey among 50 experienced Dutch psychiatrists to assess how often specific treatment strategies have been applied in the past 12 months, as well as their knowledge and expectations with respect to medication discontinuation. Results Psychiatrists estimated that, after remission, they continued medication at the same dose for at least 12 months in 51.2% of cases, continued in a reduced dose in 33.8% of cases and discontinued medication in 9.1% of cases after 4.4 months of remission on average. Although the medication is discontinued in only a relatively small proportion of patients, almost half of all clinicians (45.9%) used this strategy at least once in the past 12 months. Conclusions There is substantial practice variation in antipsychotic medication strategies after remission from a first psychotic episode. Future research on long-term effects of early medication discontinuation can guide clinicians in making evidence-based decisions when treating first-episode patients

Genetic structure of Cercospora beticola populations on Beta vulgaris in New York and Hawaii

Cercospora leaf spot (CLS), caused by Cercospora beticola, is a major disease of Beta vulgaris worldwide. No sexual stage is known for C. beticola but in its asexual form it overwinters on infected plant debris as pseudostromata, and travels short distances by rain splash-dispersed conidiospores. Cercospora beticola infects a broad range of host species and may be seedborne. The relative contribution of these inoculum sources to CLS epidemics on table beet is not well understood. Pathogen isolates collected from table beet, Swiss chard and common lambsquarters in mixed-cropping farms and monoculture fields in New York and Hawaii, USA, were genotyped (n = 600) using 12 microsatellite markers. All isolates from CLS symptoms on lambsquarters were identified as C. chenopodii. Sympatric populations of C. beticola derived from Swiss chard and table beet were not genetically differentiated. Results suggested that local (within field) inoculum sources may be responsible for the initiation of CLS epidemics in mixed-cropping farms, whereas external sources of inoculum may be contributing to CLS epidemics in the monoculture fields in New York. New multiplex PCR assays were developed for mating-type determination for C. beticola. Implications of these findings for disease management are discussed

Anticholinergic and Sedative Medications and Dynamic Gait Parameters in Older Patients

BACKGROUND: Anticholinergic and sedative medications are associated with poorer physical function in older age. Gait and physical function have traditionally been assessed with the time needed to execute objective function tests. Accelerometer-based gait parameters provide a precise capturing of gait dynamics and patterns and as such have added value. OBJECTIVES: This study examined the associations between cumulative exposure to anticholinergic and sedative medications and gait dimensions as assessed with accelerometer-based dynamic gait parameters. METHODS: Data were collected from outpatients of a diagnostic geriatric day clinic who underwent a comprehensive geriatric assessment (CGA). Cumulative exposure to anticholinergic and sedative medications was quantified with the Drug Burden Index (DBI), a linear additive pharmacological dose-response model. From a total of 22 dynamic gait parameters, the gait dimensions 'Regularity', 'Complexity', 'Stability', 'Pace', and 'Postural Control' were derived using factor analysis (and standardized total scores for these dimensions were calculated accordingly). Data were analyzed with multivariable linear regression analysis, in which adjustment was made for the covariates age, gender, body mass index (BMI), Mini Mental State Examination (MMSE) score, Charlson Comorbidity Index (CCI) including dementia, and number of medications not included in the DBI. RESULTS: A total of 184 patients participated, whose mean age was 79.8 years (± SD 5.8), of whom 110 (60%) were women and of whom 88 (48%) had polypharmacy (i.e., received treatment with ≥5 medications). Of the 893 medications that were prescribed in total, 157 medications (17.6%) had anticholinergic and/or sedative properties. Of the patients, 100 (54%) had no exposure (DBI = 0), 42 (23%) had moderate exposure (0 > DBI ≤ 1), while another 42 (23%) had high exposure (DBI >1) to anticholinergic and sedative medications. Findings showed that high cumulative exposure to anticholinergic and sedative medications was related with poorer function on the Regularity and Pace dimensions. Furthermore, moderate and high exposure were associated with poorer function on the Complexity dimension. CONCLUSIONS: These findings show that in older patients with comorbidities, cumulative anticholinergic and sedative exposure is associated with poorer function on multiple gait dimensions