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1.
Arch Sex Behav ; 49(7): 2341-2352, 2020 10.
Article in English | MEDLINE | ID: mdl-32623541

ABSTRACT

This article provides a queer theoretical reflection on the emergence of lesbian, gay, and queer (LGQ) youth as subjects of policy attention in Australia in the late twentieth century. In particular, it focuses on the ways in which specific forms of social, bureaucratic, and organizational recognition have given shape to LGQ youth as categorical policy objects. To this end, this article critically interrogates social policy related to the provision of funding for LGQ youth support during the 1980s and 1990s in two Australian states: New South Wales and Western Australia. More specifically, it focuses on some of the ways in which LGQ youth have been discursively shaped and materially supported in three different organizations, two of which continue to be strongly associated with support of LGQ youth in Australia. This study of the emergence of these organizations, resourced by three different sectors-the state, the church, and the LGQ community itself-necessarily draws on ephemeral resources, reflecting the conditions of possibility in which this work was being enacted. We conclude with an analysis of the necessity for situating policy recognitions within specific contexts to examine the implications for LGQ youth as the subjects such recognitions simultaneously seek to constitute and serve.


Subject(s)
Homosexuality/psychology , Public Policy/legislation & jurisprudence , Adolescent , Australia , Female , History, 20th Century , Humans , Male , Sexual and Gender Minorities/psychology
2.
Cult Health Sex ; 22(3): 321-335, 2020 03.
Article in English | MEDLINE | ID: mdl-30977702

ABSTRACT

Gender- and sexually diverse youth are often represented in popular discourses through concepts of movement and mobility. Conceptual stories of LGBTQ youth transitions to adulthood in particular are marked by narratives of movement from regional (rural and/or small towns) to major urban areas. Although not wholly outside lived experience, a cultural myth that portrays the experience of gender- and sexually diverse young people entering into 'adulthood' via such mobility continues to circulate in scholarship, popular media, personal accounts of coming out, support resources and self-help guidance documents. This paper draws on a recent study of gender and sexual diversity, support and belonging to examine instances of LGBTQ youth mobility in relation to participant interviews and focus groups undertaken in an Australian project examining two generations of sexually diverse subjects' views on growing up, support and belonging. Participants differed generationally in how they experienced mobility from regional to urban settings, demonstrating that contemporary real-world accounts of such mobility are complex, nuanced and diverse and that the felt 'expectation' that one should migrate to a city in order to live a full gender- or sexually diverse life has waned among young people in the more recent generation.


Subject(s)
Mass Media , Rural Population , Sexual Behavior/psychology , Sexual and Gender Minorities/psychology , Urban Population , Adolescent , Adult , Australia , Female , Focus Groups , Humans , Internet , Interviews as Topic , Male , Young Adult
3.
Foot Ankle Surg ; 26(5): 480-486, 2020 Jul.
Article in English | MEDLINE | ID: mdl-31229349

ABSTRACT

Fractures of the navicular are uncommon. This review focusses on the anatomy, classification, surgical management, post-operative rehabilitation, and outcomes of tarsal navicular fractures, to better inform decision making for clinicians managing these injuries. This review does not discuss navicular stress fractures because of the differing aetiology compared to other fractures of the navicular.


Subject(s)
Ankle Injuries/surgery , Disease Management , Fracture Fixation/methods , Fractures, Stress/surgery , Tarsal Bones/surgery , Ankle Injuries/diagnosis , Fractures, Stress/diagnosis , Humans , Tarsal Bones/diagnostic imaging , Tarsal Bones/injuries , Tomography, X-Ray Computed
4.
J Arthroplasty ; 34(5): 987-990, 2019 05.
Article in English | MEDLINE | ID: mdl-30824292

ABSTRACT

BACKGROUND: Intraoperative femur fractures are a common complication of revision hip arthroplasty. This study examined the use of a prophylactic cable in stopping a crack from propagating beyond the cable. METHODS: Seventy sheep femora were prepared. A 5-mm vertical incision was performed. Using a force-controlled materials testing machine, a Wagner shaft was advanced until a crack occurred. Cracks were visualized with green ink. In the first part, the control group without any cable (n = 10) was compared with polyethylene (n = 15) and single CoCr cable (n = 15) groups. The cables were positioned 15 mm distal to the osteotomy. In the second part, three different CoCr configurations were compared, single-wrapped (n = 15), double-wrapped (n = 125), and two separate cables at 10 and 15 mm distal to the osteotomy (n = 15). RESULTS: The polyethylene cable stopped only 3 of 15 cracks (20%), whereas the CoCr cable stopped 11 of 15 cracks (73%) (P = .009). The force needed to initiate the crack between the different groups was not significant. Twelve (80%) of 15 cracks were stopped at the level of the cable with two separate CoCr cables and 15 (100%) of 15 cracks with a double-wrapped cable (P = .11). CONCLUSION: This study demonstrated that an elastic cable is not suitable for preventive cabling. The force required to form a crack is not improved with the use of a prophylactic cable placed 10-15 mm below the osteotomy. While the results on the different configurations were not conclusive, the double-wrapped cable was able to stop all cracks from progressing distally.


Subject(s)
Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Hip/instrumentation , Femoral Fractures/prevention & control , Femur/surgery , Periprosthetic Fractures/prevention & control , Animals , Biocompatible Materials , Biomechanical Phenomena , Chromium Alloys , Femoral Fractures/etiology , Femur/injuries , Humans , Materials Testing , Osteotomy/adverse effects , Osteotomy/methods , Periprosthetic Fractures/etiology , Polyethylene , Sheep
5.
Bioorg Med Chem Lett ; 28(5): 979-984, 2018 03 01.
Article in English | MEDLINE | ID: mdl-29254646

ABSTRACT

6,7-Dihydro-5H-2,1-benzisoxazol-4-one analogs are potent inhibitors of aldosterone synthase (CYP11B2) with selectivity over the highly homologous enzyme cortisol synthase (CYP11B1). These compounds are unique among inhibitors of CYP11B2 in their lack of a strong-heme binding group such as a pyridine or imidazole. Poor metabolic stability in hepatocyte incubations was found to proceed via a reduction of the isoxazole ring. While the enzyme responsible for the reductive metabolism remains unknown, the rate of metabolism could be attenuated by the addition of polar functionality. The in vitro CYP11B2 potency and selectivity were confirmed in vivo in a cynomolgus monkey model by the inhibition of ACTH stimulated aldosterone production without impacting plasma cortisol concentrations.


Subject(s)
Cytochrome P-450 CYP11B2/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Isoxazoles/pharmacology , Cytochrome P-450 CYP11B2/metabolism , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Humans , Isoxazoles/chemical synthesis , Isoxazoles/chemistry , Molecular Structure , Structure-Activity Relationship
6.
J Immunol ; 193(11): 5525-33, 2014 Dec 01.
Article in English | MEDLINE | ID: mdl-25348623

ABSTRACT

The developmental pathways of regulatory T cells (T(reg)) generation in the thymus are not fully understood. In this study, we reconstituted thymic development of Zap70-deficient thymocytes with a tetracycline-inducible Zap70 transgene to allow temporal dissection of T(reg) development. We find that T(reg) develop with distinctive kinetics, first appearing by day 4 among CD4 single-positive (SP) thymocytes. Accepted models of CD25(+)Foxp3(+) T(reg) selection suggest development via CD25(+)Foxp3(-) CD4 SP precursors. In contrast, our kinetic analysis revealed the presence of abundant CD25(-)Foxp3(+) cells that are highly efficient at maturing to CD25(+)Foxp3(+) cells in response to IL-2. CD25(-)Foxp3(+) cells more closely resembled mature T(reg) both with respect to kinetics of development and avidity for self-peptide MHC. These population also exhibited distinct requirements for cytokines during their development. CD25(-)Foxp3(+) cells were IL-15 dependent, whereas generation of CD25(+)Foxp3(+) specifically required IL-2. Finally, we found that IL-2 and IL-15 arose from distinct sources in vivo. IL-15 was of stromal origin, whereas IL-2 was of exclusively from hemopoetic cells that depended on intact CD4 lineage development but not either Ag-experienced or NKT cells.


Subject(s)
Blood Cells/metabolism , Interleukin-15/metabolism , Interleukin-2/metabolism , Stromal Cells/metabolism , T-Lymphocytes, Regulatory/immunology , Animals , CD4 Antigens/metabolism , Cell Differentiation , Cell Lineage , Cells, Cultured , Forkhead Transcription Factors , Interleukin-2 Receptor alpha Subunit/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , T-Lymphocytes, Regulatory/transplantation , Thymus Gland/immunology , Transplantation Chimera , ZAP-70 Protein-Tyrosine Kinase/genetics
7.
J Am Chem Soc ; 136(29): 10206-9, 2014 Jul 23.
Article in English | MEDLINE | ID: mdl-25000137

ABSTRACT

Structurally ordered Pt3Ti or Pt3V intermetallic nanoparticle catalysts with ultrasmall particle sizes have never been successfully synthesized. Herein, we present a KCl-nanoparticle method to successfully provide such compounds. These two catalysts show enhanced catalytic activity and stability for methanol oxidation compared to pure Pt.

8.
Behav Sci Law ; 32(5): 627-40, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25328069

ABSTRACT

The current study investigated factors associated with voluntary and involuntary readmissions to forensic hospitals 356 insanity acquittees on conditional release in the state of Maryland from 2007, 2008, and 2009 and monitored their community progress for a 3-year follow-up period. The results indicated that voluntarily readmitted insanity acquittees had fewer reported arrests on conditional release and fewer reported instances of non-compliance with treatment compared with insanity acquittees who were returned involuntarily to hospital. As expected, arrests and treatment non-compliance predicted involuntary readmission. A third group of insanity acquittees who were not readmitted on conditional release presented with numerous differences compared with voluntarily and involuntarily readmitted acquittees. These included a longer duration in the community prior to any psychiatric readmission and fewer community psychiatric admissions than both the voluntary and involuntary groups. Data from this study provide useful information on where community monitoring resources for insanity acquittees may best be allocated.


Subject(s)
Commitment of Mentally Ill/statistics & numerical data , Insanity Defense/statistics & numerical data , Mental Disorders , Patient Admission/statistics & numerical data , Patient Readmission/statistics & numerical data , Adult , Aged , Aged, 80 and over , Crime/statistics & numerical data , Female , Housing/statistics & numerical data , Humans , Male , Maryland , Middle Aged , Retrospective Studies , Risk Factors , Young Adult
9.
New Dir Stud Leadersh ; 2024(182): 107-118, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38837677

ABSTRACT

Student employment is a common co-curricular activity among undergraduate students. Previous studies have primarily focused on the impact of employment on academic outcomes and post-graduation labor market success. Although there is an assumption that on-campus student employment influences leadership learning, there is a lack of research directly exploring this topic. Therefore, this study explores how on-campus student employment influences leadership capacity development in undergraduate students who worked in a department in Student Affairs. Findings suggest that on-campus student employment influenced leadership capacity development in undergraduate students.


Subject(s)
Employment , Leadership , Students , Humans , Young Adult , Universities , Adult , Female , Male
10.
Injury ; 55(2): 111237, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38096747

ABSTRACT

INTRODUCTION: It is only in recent years that major trauma systems and networks have been operating in the UK. High-quality data is available from the Trauma Audit and Research Network (TARN) database, enabling regional analysis. Our aim was to analyse Trauma Team Activations within the Cheshire and Merseyside major trauma network and discuss the implications of these data on resource allocation, training and trauma prevention. METHODS: A retrospective analysis was performed for all patients requiring Trauma Team Activation (TTA) at a category one adult Major Trauma Centre (MTC) who were submitted to the TARN database from the 1st January 2015 to the 1st January 2020. Data collected included the date and time of arrival, location of injury and Injury Severity Score (ISS) in addition to routine demographic data. Dates of major sporting events and school holidays were obtained. RESULTS: 4811 patients were identified. The median age was 57 years; 65.8 % were male. The mean frequency of TTAs was 18.5 per week. Patterns identified include annual peaks during the summer months, October and December, weekly peaks on Thursdays and Sundays and daily peaks between 16:00 and 23:59 with 45.0 % of TTAs occurring between these hours. There were 5.9 additional TTAs per week during the Isle of Man TT races. The median ISS increased from 14 to 23 for TT race TTAs and from 14 to 36 for Manx Grand Prix TTAs. Those injured during the TT races were twice as likely to require surgery and those injured during the MGP required five additional days in intensive care. School holidays did not independently affect major trauma volumes. CONCLUSIONS: Major trauma in Cheshire and Merseyside did follow distinct patterns according to calendar month, day and time. Major motorsport increased trauma volumes and severity; school holidays did not. Such analysis could enable Major Trauma Centres to tailor the supply of trauma services to meet a predictable local demand for the benefit of our staff and patients.


Subject(s)
Trauma Centers , Wounds and Injuries , Adult , Humans , Male , Middle Aged , Female , Retrospective Studies , Hospitalization , Injury Severity Score , Databases, Factual , Wounds and Injuries/epidemiology , Wounds and Injuries/therapy
11.
Psychol Rep ; : 332941231199456, 2023 Aug 29.
Article in English | MEDLINE | ID: mdl-37643627

ABSTRACT

As leaders across organizational contexts continue to face volatile and often stressful environments, a greater understanding of the psychological underpinnings of the motivation to lead (MTL) in challenging circumstances is needed. Based on a sample of 242 cadets holding leadership positions in a military college, we utilized a distal and proximal conceptualization of MTL to test achievement values, grit, and psychological capital (PsyCap) as antecedents to the three factors of MTL. Controlling for gender, prior leadership positions, and leader tenure, regression modeling revealed grit and achievement values to be positively associated with affective/identity MTL, while PsyCap was positively associated with all three MTL factors. In addition, PsyCap mediated the relation between grit and all three MTL factors. Our findings suggest that PsyCap plays a critical proximal role in MTL in demanding environments, and further implications for research and practice are discussed.

12.
Hum Vaccin Immunother ; 19(3): 2281717, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37965729

ABSTRACT

We examined perceptions of vaccines and changes during the coronavirus disease 2019 (COVID-19) pandemic. From 2019 to 2021, a national sample of young gay, bisexual, and other men who have sex with men completed an open-ended survey item about vaccine perceptions. Analyses identified themes and polarity (negative, neutral, or positive) within responses and determined temporal changes across phases of the pandemic ("pre-pandemic," "pandemic," "initial vaccine availability," or "widespread vaccine availability"). Themes included health benefits of vaccines (53.9%), fear of shots (23.7%), COVID-19 (10.3%), vaccines being safe (5.6%), and vaccine hesitancy/misinformation (5.5%). Temporal changes existed for multiple themes (p < .05). Overall, 53.0% of responses were positive, 31.2% were negative, and 15.8% were neutral. Compared to the pre-pandemic phase, polarity was less positive for the widespread vaccine availability phase (odds ratio = 0.64, 95% confidence interval: 0.42-0.96). The findings provide insight into how vaccine perceptions change in concert with a public health emergency.


Subject(s)
COVID-19 , Papillomavirus Vaccines , Sexual and Gender Minorities , Vaccines , Male , Humans , Homosexuality, Male , Pandemics/prevention & control , COVID-19/epidemiology , COVID-19/prevention & control , Vaccination
13.
Article in English | MEDLINE | ID: mdl-37444152

ABSTRACT

It is an assumption that physically active adults lead an overall healthy lifestyle. To examine this assumption, we administered a cross-sectional, web-based survey to a sample of young-to-middle-aged US adults between 18 and 49 who self-reported participation in at least one recreational sporting event in the past month. Logistic regressions were conducted to examine demographic characteristics associated with cancer risk and protective behaviors. Gender was represented equally (N = 938), and the average age was 32 years (SD: 8.4). Most participants reported >three days of moderate- to high-intensity physical activity (79%), but not meeting fruit and vegetable consumption guidelines (78%). Many reported current tobacco use (32%), binge drinking at least once in the past 30 days (62%), and suboptimal sun protection use (67%). Participation in lifestyle-related cancer risk and protective behaviors varied based on age, sex, education, routine doctor visits, perceived overall health, health-information-seeking behavior (how participants obtained health information), or team-based sport participation in regression models. Future interventions should be tailored to address varied cancer risk profiles among even physically active adults to encourage multiple healthy behavior changes.


Subject(s)
Neoplasms , Middle Aged , Adult , Humans , Cross-Sectional Studies , Neoplasms/epidemiology , Neoplasms/prevention & control , Life Style , Health Behavior , Fruit
14.
Front Neurosci ; 17: 1169187, 2023.
Article in English | MEDLINE | ID: mdl-37332862

ABSTRACT

Introduction: MicroCT of the three-dimensional fascicular organization of the human vagus nerve provides essential data to inform basic anatomy as well as the development and optimization of neuromodulation therapies. To process the images into usable formats for subsequent analysis and computational modeling, the fascicles must be segmented. Prior segmentations were completed manually due to the complex nature of the images, including variable contrast between tissue types and staining artifacts. Methods: Here, we developed a U-Net convolutional neural network (CNN) to automate segmentation of fascicles in microCT of human vagus nerve. Results: The U-Net segmentation of ~500 images spanning one cervical vagus nerve was completed in 24 s, versus ~40 h for manual segmentation, i.e., nearly four orders of magnitude faster. The automated segmentations had a Dice coefficient of 0.87, a measure of pixel-wise accuracy, thus suggesting a rapid and accurate segmentation. While Dice coefficients are a commonly used metric to assess segmentation performance, we also adapted a metric to assess fascicle-wise detection accuracy, which showed that our network accurately detects the majority of fascicles, but may under-detect smaller fascicles. Discussion: This network and the associated performance metrics set a benchmark, using a standard U-Net CNN, for the application of deep-learning algorithms to segment fascicles from microCT images. The process may be further optimized by refining tissue staining methods, modifying network architecture, and expanding the ground-truth training data. The resulting three-dimensional segmentations of the human vagus nerve will provide unprecedented accuracy to define nerve morphology in computational models for the analysis and design of neuromodulation therapies.

15.
J Health Serv Res Policy ; 27(1): 41-49, 2022 01.
Article in English | MEDLINE | ID: mdl-34233536

ABSTRACT

OBJECTIVE: It is increasingly recognized that patient safety requires heterogeneous insights from a range of stakeholders, yet incident reporting systems in health care still primarily rely on staff perspectives. This paper examines the potential of combining insights from patient complaints and staff incident reports for a more comprehensive understanding of the causes and severity of harm. METHODS: Using five years of patient complaints and staff incident reporting data at a large multi-site hospital in London (in the United Kingdom), this study conducted retrospective patient-level data linkage to identify overlapping reports. Using a combination of quantitative coding and in-depth qualitative analysis, we then compared level of harm reported, identified descriptions of adjacent events missed by the other party and examined combined narratives of mutually identified events. RESULTS: Incidents where complaints and incident reports overlapped (n = 446, reported in 7.6%' of all complaints and 0.6% of all incident reports) represented a small but critical area of investigation, with significantly higher rates of Serious Incidents and severe harm. Linked complaints described greater harm from safety incidents in 60% of cases, reported many surrounding safety events missed by staff (n = 582), and provided contesting stories of why problems occurred in 46% cases, and complementary accounts in 26% cases. CONCLUSIONS: This study demonstrates the value of using patient complaints to supplement, test, and challenge staff reports, including to provide greater insight on the many potential factors that may give rise to unsafe care. Accordingly, we propose that a more holistic analysis of critical safety incidents can be achieved through combining heterogeneous data from different viewpoints, such as through the integration of patient complaints and staff incident reporting data.


Subject(s)
Patient Safety , Risk Management , Data Collection , Hospitals , Humans , Retrospective Studies
16.
Sci Adv ; 7(37): eabe9733, 2021 Sep 10.
Article in English | MEDLINE | ID: mdl-34516870

ABSTRACT

Living plants provide an opportunity to rethink the design and fabrication of devices ordinarily produced from plastic and circuit boards and ultimately disposed of as waste. The spongy mesophyll is a high -surface area composition of parenchyma cells that supports gas and liquid exchange through stomata pores within the surface of most leaves. Here, we investigate the mesophyll of living plants as biocompatible substrates for the photonic display of thin nanophosphorescent films for photonic applications. Size-sorted, silica-coated 650 ± 290 -nm strontium aluminate nanoparticles are infused into five diverse plant species with conformal display of 2-µm films on the mesophyll enabling photoemission of up to 4.8 × 1013 photons/second. Chlorophyll measurements over 9 days and functional testing over 2 weeks at 2016 excitation/emission cycles confirm biocompatibility. This work establishes methods to transform living plants into photonic substrates for applications in plant-based reflectance devices, signaling, and the augmentation of plant-based lighting.

17.
Nat Commun ; 12(1): 1742, 2021 03 19.
Article in English | MEDLINE | ID: mdl-33741975

ABSTRACT

A highly protective vaccine will greatly facilitate achieving and sustaining malaria elimination. Understanding mechanisms of antibody-mediated immunity is crucial for developing vaccines with high efficacy. Here, we identify key roles in humoral immunity for Fcγ-receptor (FcγR) interactions and opsonic phagocytosis of sporozoites. We identify a major role for neutrophils in mediating phagocytic clearance of sporozoites in peripheral blood, whereas monocytes contribute a minor role. Antibodies also promote natural killer cell activity. Mechanistically, antibody interactions with FcγRIII appear essential, with FcγRIIa also required for maximum activity. All regions of the circumsporozoite protein are targets of functional antibodies against sporozoites, and N-terminal antibodies have more activity in some assays. Functional antibodies are slowly acquired following natural exposure to malaria, being present among some exposed adults, but uncommon among children. Our findings reveal targets and mechanisms of immunity that could be exploited in vaccine design to maximize efficacy.


Subject(s)
Immunity, Humoral , Malaria/immunology , Malaria/prevention & control , Receptors, IgG/immunology , Sporozoites/immunology , Adult , Aged , Antibodies, Protozoan/immunology , Child , Female , Humans , Kenya , Malaria Vaccines/immunology , Male , Middle Aged , Monocytes/immunology , Neutrophils/immunology , Phagocytosis/immunology , Plasmodium falciparum/immunology , Receptors, IgG/metabolism , THP-1 Cells , Young Adult
18.
Genome ; 53(11): 1017-23, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21076517

ABSTRACT

Association mapping currently relies on the identification of genetic markers. Several technologies have been adopted for genetic marker analysis, with single nucleotide polymorphisms (SNPs) being the most popular where a reasonable quantity of genome sequence data are available. We describe several tools we have developed for the discovery, annotation, and visualization of molecular markers for association mapping. These include autoSNPdb for SNP discovery from assembled sequence data; TAGdb for the identification of gene specific paired read Illumina GAII data; CMap3D for the comparison of mapped genetic and physical markers; and BAC and Gene Annotator for the online annotation of genes and genomic sequences.


Subject(s)
Chromosome Mapping/methods , Crops, Agricultural/genetics , Genome, Plant , Genome-Wide Association Study/methods , Base Sequence , DNA, Plant/genetics , Expressed Sequence Tags , Genetic Markers/genetics , Polymorphism, Single Nucleotide , Sequence Analysis, DNA
19.
J Am Mosq Control Assoc ; 36(3): 131-138, 2020 09 01.
Article in English | MEDLINE | ID: mdl-33600581

ABSTRACT

Climate change projections indicate that mosquito distributions will expand to include new areas of North America, increasing human exposure to mosquito-borne disease. Controlling these vectors is imperative, as mosquito-borne disease incidence will rise in response to expansion of mosquito range and increased seasonality. One means of mosquito control used in the USA is the biocontrol agent, Toxorhynchites rutilus. Climate change will open new habitats for its use by vector control organizations, but the extent of this change in habitat is currently unknown. We used a maximum entropy approach to create species distribution models for Tx. rutilus under 4 climate change scenarios by 2070. Mean temperature of warmest quarter (22.6°C to 29.1°C), annual precipitation (1,025.15 mm to 1,529.40 mm), and precipitation seasonality (≤17.86) are the most important bioclimatic variables for suitable habitat. The center of current possible habitat distribution of Tx. rutilus is in central Tennessee. Depending upon the scenario, we expect centroids to shift north-northeast by 97.68 km to 280.16 km by 2070. The extreme change in area of greater than 50% suitable habitat probability is 141.14% with 99.44% area retained. Our models indicate limited change in current habitat as well as creation of new habitat. These results are promising for North American mosquito control programs for the continued and potential combat of vector mosquitoes using Tx. rutilus.


Subject(s)
Animal Distribution , Culicidae/physiology , Mosquito Control , Animals , Biological Control Agents , Climate Change , United States
20.
Bioorg Med Chem Lett ; 19(19): 5547-51, 2009 Oct 01.
Article in English | MEDLINE | ID: mdl-19716697

ABSTRACT

An SAR study that identified a series of thienopyridine-based potent IkappaB Kinase beta (IKKbeta) inhibitors is described. With focuses on the structural optimization at C4 and C6 of structure 1 (Fig. 1), the study reveals that small alkyl and certain aromatic groups are preferred at C4, whereas polar groups with proper orientation at C6 efficiently enhance compound potency. The most potent analogues inhibit IKKbeta with IC50s as low as 40 nM, suppress LPS-induced TNF-alpha production in vitro and in vivo, display good kinase selectivity profiles, and are active in a HeLa cell NF-kappaB reporter gene assay, demonstrating that they directly interfere with the NF-kappaB signaling pathway.


Subject(s)
I-kappa B Kinase/antagonists & inhibitors , Protein Kinase Inhibitors/chemistry , Pyridines/chemistry , Animals , Drug Discovery , HeLa Cells , Humans , I-kappa B Kinase/metabolism , Lipopolysaccharides/pharmacology , Mice , NF-kappa B/metabolism , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/pharmacology , Pyridines/chemical synthesis , Pyridines/pharmacology , Signal Transduction , Structure-Activity Relationship , Tumor Necrosis Factor-alpha/metabolism
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