Balancing charge-transfer strength and triplet states for deep-blue thermally activated delayed fluorescence with an unconventional electron rich dibenzothiophene acceptor

Manipulation of the emission properties of deep-blue emitters exhibiting thermally activated delayed fluorescence (TADF) through molecular design is challenging. We present an effective strategy to probe deeper into the role of localized (LE) and charge transfer (CT) states in the reverse intersystem crossing (RISC) mechanism. In a series of donor–acceptor–donor (D–A–D) blue emitters the dibenzothiophene functionality is used as an unconventional acceptor, while derivatives of 9,10-dihydro-9,9-dimethylacridine are used as electron-donors. tert-Butyl and methoxy substituents in the para-positions of the donor greatly enhance the donor strength, which allows exploration of different energy alignments among CT and LE triplet states. In the tert-butyl substituted compound the low energy triplet is localized on the acceptor unit, with the RISC mechanism (kRISC = 0.17 × 105 s−1) likely involving the mixture of CT and LE triplet states that are separated by less than 0.09 eV. An optimized organic light-emitting diode (OLED) based on the tBu-compound presents a maximum external quantum efficiency of 10.5% and deep-blue emission with Commission Internationale de l'Eclairage coordinates of (0.133, 0.129). However, when methoxy substituents are used, the low-energy triplet state moves away from the emissive 1CT singlet increasing the energy gap to 0.24 eV. Despite a larger ΔEST, a faster RISC rate (kRISC = 2.28 × 105 s−1) is observed due to the upper-state RISC occurring from the high-energy triplet state localized on the D (or A) units. This work shows the importance of fine-tuning the electronic interactions of the donor and acceptor units to control the TADF mechanism and achieve a deep-blue TADF OLED

Development of ERAU VOLTRON Hybrid-Electric Powerplant

The energy density of today’s batteries is not high enough for electric powered aircraft to achieve an operationally viable range plus FAA stipulated reserve flight times. Hybrid-electric power generation systems may be able to bridge the gap, providing a way for these aircraft to fly distances not possible with batteries alone. There is a recognition that gasoline-electric hybrid systems can deliver specific energy and specific power that are higher than any currently available battery system. Embry-Riddle Aeronautical University’s (ERAU’s) Eagle Flight Research Center (EFRC) is building a 70+ kW hybrid-electric power generation system using a rotary engine and Permanent Magnet Synchronous Machine (PMSM) & Inverter. The rotary engine will be directly coupled to the PMSM which will generate electrical energy to power multi-rotor eVTOL vehicles. These results will be achieved by utilizing advanced control systems implemented on a National Instruments Compact RIO. Past research conducted at the EFRC demonstrated the ability to design and operate a hybrid-electric powerplant. The VOLTRON project will attempt to create a system with an even higher specific energy but with the compact size and high power characteristics of a rotary engine and eventually alternative fuel flexibility

Aspergillus mastoiditis, presenting with unexplained progressive otalgia, in an immunocompetent (older) patient

Aspergillus mastoidits and skull-base osteomyelitis are extremely rare, even in immunocompromised patients. We report a case of an 81-year-old immunocompetent man, who underwent a mastoidectomy because of unexplained, progressive otalgia in spite of a noninflamed and air-containing middle-ear space. Histopathology yielded Aspergillus fumigatus. When confronted with otitis with an unexpected clinical course a high index of suspicion is required to facilitate early diagnosis and appropriate therapy of a potential lethal Aspergillus infection, even in immunocompetent patients. This seems to be more so in older patients with an open middle-ear cavity and/or when there is facial nerve involvement

A new satellite RNA is associated with natural infections of cucumber mosaic virus in succulent snap bean

Cucumber mosaic virus (CMV) was consistently recovered from symptomatic snap bean plants during surveys conducted in 2007 and 2008 in central Wisconsin. A large proportion of these CMV-infected plants contained a single-stranded linear RNA molecule consisting of 339 nucleotides and sharing 90–94% sequence identity with other satellite (sat) RNAs of CMV. Comparison of this satRNA sequence with currently available CMV satRNA sequences suggests this to be a novel satRNA

Improved Malaria Case Management through the Implementation of a Health Facility-Based Sentinel Site Surveillance System in Uganda

Heath facility-based sentinel site surveillance has been proposed as a means of monitoring trends in malaria morbidity but may also provide an opportunity to improve malaria case management. Here we described the impact of a sentinel site malaria surveillance system on promoting laboratory testing and rational antimalarial drug use.Sentinel site malaria surveillance was established at six health facilities in Uganda between September 2006 and January 2007. Data were collected from all patients presenting to the outpatient departments including demographics, laboratory results, diagnoses, and treatments prescribed. Between the start of surveillance and March 2010, a total 424,701 patients were seen of which 229,375 (54%) were suspected of having malaria. Comparing the first three months with the last three months of surveillance, the proportion of patients with suspected malaria who underwent diagnostic testing increased from 39% to 97% (p<0.001). The proportion of patients with an appropriate decision to prescribe antimalarial therapy (positive test result prescribed, negative test result not prescribed) increased from 64% to 95% (p<0.001). The proportion of patients appropriately prescribed antimalarial therapy who were prescribed the recommended first-line regimen artemether-lumefantrine increased from 48% to 69% (p<0.001).The establishment of a sentinel site malaria surveillance system in Uganda achieved almost universal utilization of diagnostic testing in patients with suspected malaria and appropriate decisions to prescribed antimalarial based on test results. Less success was achieved in promoting prescribing practice for the recommended first-line therapy. This system could provide a model for improving malaria case management in other health facilities in Africa

Integration of priority population, health and nutrition interventions into health systems: systematic review

Objective of the study was to assess the effects of strategies to integrate targeted priority population, health and nutrition interventions into health systems on patient health outcomes and health system effectiveness and thus to compare integrated and non-integrated health programmes. Systematic review using Cochrane methodology of analysing randomised trials, controlled before-and-after and interrupted time series studies. We defined specific strategies to search PubMed, CENTRAL and the Cochrane Effective Practice and Organisation of Care Group register, considered studies published from January 1998 until September 2008, and tracked references and citations. Two reviewers independently agreed on eligibility, with an additional arbiter as needed, and extracted information on outcomes: primary (improved health, financial protection, and user satisfaction) and secondary (improved population coverage, access to health services, efficiency, and quality) using standardised, pre-piloted forms. Two reviewers in the final stage of selection jointly assessed quality of all selected studies using the GRADE criteria. Of 8,274 citations identified 12 studies met inclusion criteria. Four studies compared the benefits of Integrated Management of Childhood Illnesses in Tanzania and Bangladesh, showing improved care management and higher utilisation of health facilities at no additional cost. Eight studies focused on integrated delivery of mental health and substance abuse services in the United Kingdom and United States of America. Integrated service delivery resulted in better clinical outcomes and greater reduction of substance abuse in specific sub-groups of patients, with no significant difference found overall. Quality of care, patient satisfaction, and treatment engagement were higher in integrated delivery models. Targeted priority population health interventions we identified led to improved health outcomes, quality of care, patient satisfaction and access to care. Limited evidence with inconsistent findings across varied interventions in different settings means no general conclusions can be drawn on the benefits or disadvantages of integrated service delivery

Changes in the Policy Environment For Infant and Young Child feeding in Vietnam, Bangladesh, and Ethiopia, and the Role of Targeted Advocacy

There is limited literature examining shifts in policy environments for nutrition and infant and young child feeding (IYCF) over time, and on the potential contribution of targeted advocacy to improved policy environments in low- and middle-income countries. This study tracked changes in the policy environment over a four-year period in three countries, and examined the role of targeted nutrition and IYCF advocacy strategies by a global initiative

Extreme CD8 T Cell Requirements for Anti-Malarial Liver-Stage Immunity following Immunization with Radiation Attenuated Sporozoites

Radiation-attenuated Plasmodium sporozoites (RAS) are the only vaccine shown to induce sterilizing protection against malaria in both humans and rodents. Importantly, these “whole-parasite” vaccines are currently under evaluation in human clinical trials. Studies with inbred mice reveal that RAS-induced CD8 T cells targeting liver-stage parasites are critical for protection. However, the paucity of defined T cell epitopes for these parasites has precluded precise understanding of the specific characteristics of RAS-induced protective CD8 T cell responses. Thus, it is not known whether quantitative or qualitative differences in RAS-induced CD8 T cell responses underlie the relative resistance or susceptibility of immune inbred mice to sporozoite challenge. Moreover, whether extraordinarily large CD8 T cell responses are generated and required for protection following RAS immunization, as has been described for CD8 T cell responses following single-antigen subunit vaccination, remains unknown. Here, we used surrogate T cell activation markers to identify and track whole-parasite, RAS-vaccine-induced effector and memory CD8 T cell responses. Our data show that the differential susceptibility of RAS-immune inbred mouse strains to Plasmodium berghei or P. yoelii sporozoite challenge does not result from host- or parasite-specific decreases in the CD8 T cell response. Moreover, the surrogate activation marker approach allowed us for the first time to evaluate CD8 T cell responses and protective immunity following RAS-immunization in outbred hosts. Importantly, we show that compared to a protective subunit vaccine that elicits a CD8 T cell response to a single epitope, diversifying the targeted antigens through whole-parasite RAS immunization only minimally, if at all, reduced the numerical requirements for memory CD8 T cell-mediated protection. Thus, our studies reveal that extremely high frequencies of RAS-induced memory CD8 T cells are required, but may not suffice, for sterilizing anti-Plasmodial immunity. These data provide new insights into protective CD8 T cell responses elicited by RAS-immunization in genetically diverse hosts, information with relevance to developing attenuated whole-parasite vaccines

Tyrosine Phosphorylation of Rac1: A Role in Regulation of Cell Spreading

Rac1 influences a multiplicity of vital cellular- and tissue-level control functions, making it an important candidate for targeted therapeutics. The activity of the Rho family member Cdc42 has been shown to be modulated by tyrosine phosphorylation at position 64. We therefore investigated consequences of the point mutations Y64F and Y64D in Rac1. Both mutations altered cell spreading from baseline in the settings of wild type, constitutively active, or dominant negative Rac1 expression, and were accompanied by differences in Rac1 targeting to focal adhesions. Rac1-Y64F displayed increased GTP-binding, increased association with βPIX, and reduced binding with RhoGDI as compared with wild type Rac1. Rac1-Y64D had less binding to PAK than Rac1-WT or Rac1-64F. In vitro assays demonstrated that Y64 in Rac1 is a target for FAK and Src. Taken together, these data suggest a mechanism for the regulation of Rac1 activity by non-receptor tyrosine kinases, with consequences for membrane extension

A Combination of Independent Transcriptional Regulators Shapes Bacterial Virulence Gene Expression during Infection

Transcriptional regulatory networks are fundamental to how microbes alter gene expression in response to environmental stimuli, thereby playing a critical role in bacterial pathogenesis. However, understanding how bacterial transcriptional regulatory networks function during host-pathogen interaction is limited. Recent studies in group A Streptococcus (GAS) suggested that the transcriptional regulator catabolite control protein A (CcpA) influences many of the same genes as the control of virulence (CovRS) two-component gene regulatory system. To provide new information about the CcpA and CovRS networks, we compared the CcpA and CovR transcriptomes in a serotype M1 GAS strain. The transcript levels of several of the same genes encoding virulence factors and proteins involved in basic metabolic processes were affected in both ΔccpA and ΔcovR isogenic mutant strains. Recombinant CcpA and CovR bound with high-affinity to the promoter regions of several co-regulated genes, including those encoding proteins involved in carbohydrate and amino acid metabolism. Compared to the wild-type parental strain, ΔccpA and ΔcovRΔccpA isogenic mutant strains were significantly less virulent in a mouse myositis model. Inactivation of CcpA and CovR alone and in combination led to significant alterations in the transcript levels of several key GAS virulence factor encoding genes during infection. Importantly, the transcript level alterations in the ΔccpA and ΔcovRΔccpA isogenic mutant strains observed during infection were distinct from those occurring during growth in laboratory medium. These data provide new knowledge regarding the molecular mechanisms by which pathogenic bacteria respond to environmental signals to regulate virulence factor production and basic metabolic processes during infection