Dynamic response of a cracked atomic force microscope cantilever used for nanomachining

The vibration behavior of an atomic force microscope [AFM] cantilever with a crack during the nanomachining process is studied. The cantilever is divided into two segments by the crack, and a rotational spring is used to simulate the crack. The two individual governing equations of transverse vibration for the cracked cantilever can be expressed. However, the corresponding boundary conditions are coupled because of the crack interaction. Analytical expressions for the vibration displacement and natural frequency of the cracked cantilever are obtained. In addition, the effects of crack flexibility, crack location, and tip length on the vibration displacement of the cantilever are analyzed. Results show that the crack occurs in the AFM cantilever that can significantly affect its vibration response

Insights from linking police domestic abuse data and health data in South Wales, UK: a linked routine data analysis using decision tree classification

BACKGROUND: Exposure to domestic abuse can lead to long-term negative impacts on the victim's physical and psychological wellbeing. The 1998 Crime and Disorder Act requires agencies to collaborate on crime reduction strategies, including data sharing. Although data sharing is feasible for individuals, rarely are whole-agency data linked. This study aimed to examine the knowledge obtained by integrating information from police and health-care datasets through data linkage and analyse associated risk factor clusters. METHODS: This retrospective cohort study analyses data from residents of South Wales who were victims of domestic abuse resulting in a Public Protection Notification (PPN) submission between Aug 12, 2015 and March 31, 2020. The study links these data with the victims' health records, collated within the Secure Anonymised Information Linkage databank, to examine factors associated with the outcome of an Emergency Department attendance, emergency hospital admission, or death within 12 months of the PPN submission. To assess the time to outcome for domestic abuse victims after the index PPN submission, we used Kaplan-Meier survival analysis. We used multivariable Cox regression models to identify which factors contributed the highest risk of experiencing an outcome after the index PPN submission. Finally, we created decision trees to describe specific groups of individuals who are at risk of experiencing a domestic abuse incident and subsequent outcome. FINDINGS: After excluding individuals with multiple PPN records, duplicates, and records with a poor matching score or missing fields, the resulting clean dataset consisted of 8709 domestic abuse victims, of whom 6257 (71·8%) were female. Within a year of a domestic abuse incident, 3650 (41·9%) individuals had an outcome. Factors associated with experiencing an outcome within 12 months of the PPN included younger victim age (hazard ratio 1·183 [95% CI 1·053-1·329], p=0·0048), further PPN submissions after the initial referral (1·383 [1·295-1·476]; p<0·0001), injury at the scene (1·484 [1·368-1·609]; p<0·0001), assessed high risk (1·600 [1·444-1·773]; p<0·0001), referral to other agencies (1·518 [1·358-1·697]; p<0·0001), history of violence (1·229 [1·134-1·333]; p<0·0001), attempted strangulation (1·311 [1·148-1·497]; p<0·0001), and pregnancy (1·372 [1·142-1·648]; p=0·0007). Health-care data before the index PPN established that previous Emergency Department and hospital admissions, smoking, smoking cessation advice, obstetric codes, and prescription of antidepressants and antibiotics were associated with having a future outcome following a domestic abuse incident. INTERPRETATION: The results indicate that vulnerable individuals are detectable in multiple datasets before and after involvement of the police. Operationalising these findings could reduce police callouts and future Emergency Department or hospital admissions, and improve outcomes for those who are vulnerable. Strategies include querying previous Emergency Department and hospital admissions, giving a high-risk assessment for a pregnant victim, and facilitating data linkage to identify vulnerable individuals

Ecstasy use and depression: A 4-year longitudinal study among an Australian general community sample

RATIONALE: Longitudinal, population-based studies can better assess the relationship of ecstasy use with depression. OBJECTIVES: We examined whether change in ecstasy use was associated with change in depressive symptoms/probable depression over a 4-year period, among a large Australian sample. METHODS: The Personality and Total Health project is a longitudinal general community study of Australians from Canberra and Queanbeyan. Data from the youngest cohort when aged 24-30 (N = 2, 128) and 4 years later (N = 1, 977) was included. The Goldberg depression scale and the Brief Patient Health Questionnaire measured depressive symptoms and probable depression, respectively. Multilevel growth models also considered demographics, psychosocial characteristics, and other drug use. RESULTS: Ecstasy use was not associated with long-term depressive symptoms or greater odds of depression in multivariate analyses. Users had more self-reported depressive symptoms when using ecstasy compared to not using. However, differences between people who had and had not ever used ecstasy largely accounted for this. Other factors were more important in the prediction of depression. CONCLUSIONS: It would be premature to conclude that ecstasy use is not related to the development of long-term depressive symptoms, given the relatively low level of ecstasy and other drug use in this community sample. Results showed that other factors need to be considered when investigating ecstasy use and depression

Synthetic human cell fate regulation by protein-driven RNA switches

Understanding how to control cell fate is crucial in biology, medical science and engineering. In this study, we introduce a method that uses an intracellular protein as a trigger for regulating human cell fate. The ON/OFF translational switches, composed of an intracellular protein L7Ae and its binding RNA motif, regulate the expression of a desired target protein and control two distinct apoptosis pathways in target human cells. Combined use of the switches demonstrates that a specific protein can simultaneously repress and activate the translation of two different mRNAs: one protein achieves both up- and downregulation of two different proteins/pathways. A genome-encoded protein fused to L7Ae controlled apoptosis in both directions (death or survival) depending on its cellular expression. The method has potential for curing cellular defects or improving the intracellular production of useful molecules by bypassing or rewiring intrinsic signal networks

Teacher led school-based surveillance can allow accurate tracking of emerging infectious diseases - evidence from serial cross-sectional surveys of febrile respiratory illness during the H1N1 2009 influenza pandemic in Singapore

10.1186/1471-2334-12-336BMC Infectious Diseases12-BIDM

Analyses of genome architecture and gene expression reveal novel candidate virulence factors in the secretome of Phytophthora infestans

<p>Abstract</p> <p>Background</p> <p><it>Phytophthora infestans </it>is the most devastating pathogen of potato and a model organism for the oomycetes. It exhibits high evolutionary potential and rapidly adapts to host plants. The <it>P. infestans </it>genome experienced a repeat-driven expansion relative to the genomes of <it>Phytophthora sojae </it>and <it>Phytophthora ramorum </it>and shows a discontinuous distribution of gene density. Effector genes, such as members of the RXLR and Crinkler (CRN) families, localize to expanded, repeat-rich and gene-sparse regions of the genome. This distinct genomic environment is thought to contribute to genome plasticity and host adaptation.</p> <p>Results</p> <p>We used <it>in silico </it>approaches to predict and describe the repertoire of <it>P. infestans </it>secreted proteins (the secretome). We defined the "plastic secretome" as a subset of the genome that (i) encodes predicted secreted proteins, (ii) is excluded from genome segments orthologous to the <it>P. sojae </it>and <it>P. ramorum </it>genomes and (iii) is encoded by genes residing in gene sparse regions of <it>P. infestans </it>genome. Although including only ~3% <it>of P. infestans </it>genes, the plastic secretome contains ~62% of known effector genes and shows >2 fold enrichment in genes induced <it>in planta</it>. We highlight 19 plastic secretome genes induced <it>in planta </it>but distinct from previously described effectors. This list includes a trypsin-like serine protease, secreted oxidoreductases, small cysteine-rich proteins and repeat containing proteins that we propose to be novel candidate virulence factors.</p> <p>Conclusions</p> <p>This work revealed a remarkably diverse plastic secretome. It illustrates the value of combining genome architecture with comparative genomics to identify novel candidate virulence factors from pathogen genomes.</p

Expression profiling during arabidopsis/downy mildew interaction reveals a highly-expressed effector that attenuates responses to salicylic acid

Plants have evolved strong innate immunity mechanisms, but successful pathogens evade or suppress plant immunity via effectors delivered into the plant cell. Hyaloperonospora arabidopsidis (Hpa) causes downy mildew on Arabidopsis thaliana, and a genome sequence is available for isolate Emoy2. Here, we exploit the availability of genome sequences for Hpa and Arabidopsis to measure gene-expression changes in both Hpa and Arabidopsis simultaneously during infection. Using a high-throughput cDNA tag sequencing method, we reveal expression patterns of Hpa predicted effectors and Arabidopsis genes in compatible and incompatible interactions, and promoter elements associated with Hpa genes expressed during infection. By resequencing Hpa isolate Waco9, we found it evades Arabidopsis resistance gene RPP1 through deletion of the cognate recognized effector ATR1. Arabidopsis salicylic acid (SA)-responsive genes including PR1 were activated not only at early time points in the incompatible interaction but also at late time points in the compatible interaction. By histochemical analysis, we found that Hpa suppresses SA-inducible PR1 expression, specifically in the haustoriated cells into which host-translocated effectors are delivered, but not in non-haustoriated adjacent cells. Finally, we found a highly-expressed Hpa effector candidate that suppresses responsiveness to SA. As this approach can be easily applied to host-pathogen interactions for which both host and pathogen genome sequences are available, this work opens the door towards transcriptome studies in infection biology that should help unravel pathogen infection strategies and the mechanisms by which host defense responses are overcome

Synthetic biology: Understanding biological design from synthetic circuits

An important aim of synthetic biology is to uncover the design principles of natural biological systems through the rational design of gene and protein circuits. Here, we highlight how the process of engineering biological systems — from synthetic promoters to the control of cell–cell interactions — has contributed to our understanding of how endogenous systems are put together and function. Synthetic biological devices allow us to grasp intuitively the ranges of behaviour generated by simple biological circuits, such as linear cascades and interlocking feedback loops, as well as to exert control over natural processes, such as gene expression and population dynamics

Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

Chronic obstructive pulmonary disease (COPD) and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking and exert a considerable societal burden. People suffering from COPD are at higher risk of developing lung cancer than those without, and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower postoperative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we provide a detailed overview of possible underlying factors that link COPD and lung cancer, and current therapeutic advances from both human and preclinical animal models that can effectively mitigate this unholy relationship