Beyond Low-Earth Orbit: Characterizing Immune and microRNA Differentials following Simulated Deep Spaceflight Conditions in Mice

Spaceflight missions can cause immune system dysfunction in astronauts with little understanding of immune outcomes in deep space. This study assessed immune responses in mice following ground-based, simulated deep spaceflight conditions, compared with data from astronauts on International Space Station missions. For ground studies, we simulated microgravity using the hindlimb unloaded mouse model alone or in combination with acute simulated galactic cosmic rays or solar particle events irradiation. Immune profiling results revealed unique immune diversity following each experimental condition, suggesting each stressor results in distinct circulating immune responses, with clear consequences for deep spaceflight. Circulating plasma microRNA sequence analysis revealed involvement in immune system dysregulation. Furthermore, a large astronaut cohort showed elevated inflammation during low-Earth orbit missions, thereby supporting our simulated ground experiments in mice. Herein, circulating immune biomarkers are defined by distinct deep space irradiation types coupled to simulated microgravity and could be targets for future space health initiatives

Legal Marketing Through the Decades: Pitfalls of Current Marketing Trends

Historically, states did not place restrictions on advertising by professionals; it was not until the beginning of the twentieth century that jurisdictions began to enact prohibitions on marketing of professional services. Eventually, the U.S. Supreme Court recognized the right of professionals to advertise their services and has continued to define the right in the decades since. While lawyers have long advertised in traditional media, such as billboards and television, thanks to the exploding popularity of social media websites like Facebook and Twitter, the available platforms lawyers may use to market their services will continue to multiply. New and creative approaches to marketing one’s services have resulted in equally creative state measures to corral such marketing practices. Despite attempts to address the ethical implications of advertising in a constantly evolving digital media age, the ABA and state bar associations have failed to keep up. The focus of this Article is to review the evolution of marketing techniques utilized in the legal arena and report on disciplinary actions stemming from advertising practices found to be unethical and in violation of state rules of professional conduct. By examining cases where attorneys’ marketing practices have been misleading or have resulted in the inadvertent creation of attorney–client relationships, this Article demonstrates the need for further guidance regarding online marketing of legal services

Rookies Connected: Interpersonal Relationships Among Newcomers, Newcomer Adjustment Processes, and Socialization Outcomes

How do relationships among newcomers in the same cohort impact how quickly they develop clear understandings of their new roles and, ultimately, key socialization outcomes? We study newcomers\u27 relationships with cohort members in the same unit (i.e., intra-unit relationships) and those in different units (i.e., inter-unit relationships). While organizations invest substantial time and resources in promoting broad networking among newcomers, we offer a theoretical and empirical account of how too many connections among fellow newcomers early in the socialization process can slow their adjustment-namely, their growth in role clarity. In Study 1, we surveyed 189 newcomers in an international conglomerate from their orientations through their first 4 months and linked responses to 3 years of their job performance and turnover records. After controlling for the initial level of role clarity, we found an inverted U-shaped relationship between newcomers\u27 intra-unit peer connections and growth in role clarity, whereas their inter-unit peer connections did not significantly relate to growth in role clarity. Growth in role clarity positively related to subsequent newcomers\u27 job satisfaction and job performance, which were then negatively related to turnover. Study 2\u27s results indicated that sensemaking with fellow newcomers operated as a key mechanism linking the nonlinear relationships between intra-unit newcomer-newcomer relationships and growth in role clarity. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

A bayesian approach for NDT data fusion: The Saint Torcato Church case study

This paper presents a methodology based on the Bayesian data fusion techniques applied to non-destructive and destructive tests for the structural assessment of historical constructions. The aim of the methodology is to reduce the uncertainties of the parameter estimation. The Young's modulus of granite stones was chosen as an example for the present paper. The methodology considers several levels of uncertainty since the parameters of interest are considered random variables with random moments. A new concept of Trust Factor was introduced to affect the uncertainty related to each test results, translated by their standard deviation, depending on the higher or lower reliability of each test to predict a certain parameter.The authors would like to acknowledge the Fundação para a Ciência e Tecnologia, which supported this research work as a part of the Project “Improved and innovative techniques for the diagnosis and monitoring of historical masonry”, PTDC/ECM/104045/2008

A Phase I Trial of Aminolevulinic Acid-Photodynamic Therapy for Treatment of Oral Leukoplakia

Background Photodynamic therapy with aminolevulinic acid (ALA PDT) for oral leukoplakia has shown promising effects in regression of oral leukoplakia. Although ALA has been extensively studied and is an ideal photosensitizer, the optimal light dose for treatment of oral leukoplakia has not been determined. We conducted a phase I study to determine MTD and DLT of PDT in patients treated with ALA for leukoplakia. Methods Patients with histologically confirmed oral leukoplakia received a single treatment of ALA PDT in cohorts with escalating doses of light (585 nm). Clinical, histologic, and biologic markers were assessed. Results Analysis of 11 participants is reported. No significant toxicity from ALA PDT was observed in patients who received ALA with a light dose of up to 4 J/cm2. One participant experienced transient grade 3 transaminase elevation due to ALA. One participant had a partial clinical response 3 months after treatment. Biologic mucosal risk markers showed no significant associations. Determination of MTD could not be accomplished within a feasible timeframe for completion of the study. Conclusions ALA PDT could be safely administered with a light dose up to 4 J/cm2 and demonstrated activity. Larger studies are needed to fully elucidate the MTD and efficacy of ALA-PDT

Spectral Bio-indicator Simulations for Tracking Photosynthetic Activities in a Corn Field

Accurate assessment of vegetation canopy optical properties plays a critical role in monitoring natural and managed ecosystems under environmental changes. In this context, radiative transfer (RT) models simulating vegetation canopy reflectance have been demonstrated to be a powerful tool for understanding and estimating spectral bio-indicators. In this study, two narrow band spectroradiometers were utilized to acquire observations over corn canopies for two summers. These in situ spectral data were then used to validate a two-layer Markov chain-based canopy reflectance model for simulating the Photochemical Reflectance Index (PRI), which has been widely used in recent vegetation photosynthetic light use efficiency (LUE) studies. The in situ PRI derived from narrow band hyperspectral reflectance exhibited clear responses to: 1) viewing geometry which affects the asset of light environment; and 2) seasonal variation corresponding to the growth stage. The RT model (ACRM) successfully simulated the responses to the variable viewing geometry. The best simulations were obtained when the model was set to run in the two layer mode using the sunlit leaves as the upper layer and shaded leaves as the lower layer. Simulated PRI values yielded much better correlations to in situ observations when the cornfield was dominated by green foliage during the early growth, vegetative and reproductive stages (r = 0.78 to 0.86) than in the later senescent stage (r = 0.65). Further sensitivity analyses were conducted to show the important influences of leaf area index (LAI) and the sunlit/shaded ratio on PRI observations

'Relieved to be seen'-patient and carer experiences of psychosocial assessment in the emergency department following self-harm: qualitative analysis of 102 free-text survey responses.

From Europe PMC via Jisc Publications RouterHistory: ppub 2021-05-01, epub 2021-05-23Publication status: PublishedObjectivesWe sought to explore patient and carer experiences of psychosocial assessments following presentations to hospital after self-harm.DesignThematic analysis of free-text responses to an open-ended online survey.SettingBetween March and November 2019, we recruited 88 patients (82% women) and 14 carers aged ≥18 years from 16 English mental health trusts, community organisations, and via social media.ResultsPsychosocial assessments were experienced as helpful on some occasions but harmful on others. Participants felt better, less suicidal and less likely to repeat self-harm after good-quality compassionate and supportive assessments. However, negative experiences during the assessment pathway were common and, in some cases, contributed to greater distress, less engagement and further self-harm. Participants reported receiving negative and stigmatising comments about their injuries. Others reported that they were refused medical care or an anaesthetic. Stigmatising attitudes among some mental health staff centred on preconceived ideas over self-harm as a 'behavioural issue', inappropriate use of services and psychiatric diagnosis.ConclusionOur findings highlight important patient experiences that can inform service provision and they demonstrate the value of involving patients/carers throughout the research process. Psychosocial assessments can be beneficial when empathetic and collaborative but less helpful when overly standardised, lacking in compassion and waiting times are unduly long. Patient views are essential to inform practice, particularly given the rapidly changing service context during and after the COVID-19 emergency

Effects of increasing the affinity of CarD for RNA polymerase on Mycobacterium tuberculosis growth, rRNA transcription, and virulence

CarD is an essential RNA polymerase (RNAP) interacting protein in Mycobacterium tuberculosis that stimulates formation of RNAP-promoter open complexes. CarD plays a complex role in M. tuberculosis growth and virulence that is not fully understood. Therefore, to gain further insight into the role of CarD in M. tuberculosis growth and virulence, we determined the effect of increasing the affinity of CarD for RNAP. Using site-directed mutagenesis guided by crystal structures of CarD bound to RNAP, we identified amino acid substitutions that increase the affinity of CarD for RNAP. Using these substitutions, we show that increasing the affinity of CarD for RNAP increases the stability of the CarD protein in M. tuberculosis. In addition, we show that increasing the affinity of CarD for RNAP increases the growth rate in M. tuberculosis without affecting 16S rRNA levels. We further show that increasing the affinity of CarD for RNAP reduces M. tuberculosis virulence in a mouse model of infection despite the improved growth rate in vitro. Our findings suggest that the CarD-RNAP interaction protects CarD from proteolytic degradation in M. tuberculosis, establish that growth rate and rRNA levels can be uncoupled in M. tuberculosis and demonstrate that the strength of the CarD-RNAP interaction has been finely tuned to optimize virulence. IMPORTANCE Mycobacterium tuberculosis, the causative agent of tuberculosis, remains a major global health problem. In order to develop new strategies to battle this pathogen, we must gain a better understanding of the molecular processes involved in its survival and pathogenesis. We have previously identified CarD as an essential transcriptional regulator in mycobacteria. In this study, we detail the effects of increasing the affinity of CarD for RNAP on transcriptional regulation, CarD protein stability, and virulence. These studies expand our understanding of the global transcription regulator CarD, provide insight into how CarD activity is regulated, and broaden our understanding of prokaryotic transcription

LET-Dependent Low Dose and Synergistic Inhibition of Human Angiogenesis by Charged Particles: Validation of miRNAs that Drive Inhibition

Space radiation inhibits angiogenesis by two mechanisms depending on the linear energy transfer (LET). Using human 3D micro-vessel models, blockage of the early motile stage of angiogenesis was determined to occur after exposure to low LET ions (/AMU), whereas inhibition of the later stages occurs after exposure to high LET ions (\u3e8 KeV/AMU). Strikingly, the combined effect is synergistic, detectible as low as 0.06 Gy making mixed ion space radiation more potent. Candidates for bystander transmission are microRNAs (miRNAs), and analysis on miRNA-seq data from irradiated mice shows that angiogenesis would in theory be downregulated. Further analysis of three previously identified miRNAs showed downregulation of their targets associated with angiogenesis and confirmed their involvement in angiogenesis pathways and increased health risks associated with cardiovascular disease. Finally, synthetic molecules (antagomirs) designed to inhibit the predicted miRNAs were successfully used to reverse the inhibition of angiogenesis