Convergent synthesis and optical properties of near-infrared emitting bioluminescent infra-luciferins

Infra-luciferin, an alkene linked analogue of luciferin, gives bioluminescence emission >700 nm and has the potential to be used for multiparametric in vivo imaging. We report here a high yielding, scalable and convergent synthesis of infra-luciferin which will allow the synthesis of other conjugated luciferins for investigation in near-infrared bioluminescence imaging. We demonstrated this potential by using the new route to synthesise a diene linked analogue of luciferin, the fluorescent and bioluminescent properties of which were compared to those of D-luciferin and infra-luciferin. We found that extension of conjugation to a diene linker resulted in the specific bioluminescence activity being reduced by 3–4 orders of magnitude compared to D-luciferin. Analogous to its fluorescence emission spectrum, the diene linked analogue exhibited two peaks in its bioluminescence spectrum, the major one being slightly blue-shifted compared to natural D-luciferin, and a minor peak at ca. 800 nm. The fluorescence quantum yield and pH dependence of fluorescence were also determined

An Aotearoa New Zealand survey of the impact and diagnostic delay for endometriosis and chronic pelvic pain

Chronic pelvic pain (CPP) causes important negative effects on quality of life. Endometriosis is the most common cause of CPP in females, and diagnostic delay is over six years internationally. Data remain scarce for CPP impact or diagnostic delay in Aotearoa New Zealand. This study used an online survey to explore the impact of CPP on various life domains for those aged over 18. Additionally, for those with an endometriosis diagnosis, diagnostic delay and factors affecting this over time were explored. There were 800 respondent (620 with self-reported endometriosis). CPP symptoms, irrespective of final diagnosis, started prior to age 20 and negatively impacted multiple life domains including employment, education, and relationships. Mean diagnostic delay for those with endometriosis was 8.7 years, including 2.9 years between symptom onset and first presentation and 5.8 years between first presentation and diagnosis. Five doctors on average were seen prior to diagnosis. However, there was a reduction in the interval between first presentation and diagnosis over time, from 8.4 years for those presenting before 2005, to two years for those presenting after 2012. While diagnostic delay is decreasing, CPP, irrespective of aetiology, continues to have a significant negative impact on the lives of those affected

The double burden of COVID-19 and a major volcanic eruption on local food production and food security in a Small Island Developing State

IntroductionSmall Island Developing States have disproportionately high food insecurity rates, related to complex challenges and vulnerabilities. The COVID-19 pandemic highlighted that within these settings, crises often overlap. We aimed to assess the impact of the concurrent COVID-19 pandemic and volcanic eruption on food production and security in St. Vincent and the Grenadines (SVG).MethodsAn interpretive mixed-methods study was conducted among a convenience sample of consenting adults ≥18 years from 100 households in SVG through a cross-sectional survey and participant interviews (10 households) between September 2021 and March 2022. Food insecurity prevalence over the past year was assessed using the Food Insecurity Experience Scale (FIES; Rasch modeling) and impacts to livelihoods from the pandemic and volcanic eruption was assessed using an adapted Caribbean COVID-19 Food Security and Livelihoods Impact Survey (Caribbean COVID-19 FS&L Survey). Data were analyzed using logistic regression.ResultsDuring the pandemic, 59% of the participants reported decreased income, 63% had no access to markets, 81% had no access to food aid; 34% of the participants had a change in food sources, and 81% reported that food production was negatively impacted by the volcanic eruptions, of which 68% reported decreased food production. The interviews highlighted that access to markets were restricted by fear of leaving home and contracting the COVID-19 virus, and participants who received food aid stated that the number of items were not sufficient for larger families. Almost half of the participants were severely food insecure [48% (95% C.I. 31.2,57.8)]; almost two thirds were moderately to severely food insecure [64% (95% C.I. 50.0, 74.2)]; mean FIES score 5.31 (95% C.I. 5.0,5.6). After adjusting for gender, age, education, and household size, moderate to severe food insecurity was associated with no access to food aid during the pandemic and post-eruptions (odds ratio 3.7; 95% confidence interval 1.5, 9.1; p = 0.004).ConclusionFood insecurity rates were high during the COVID-19 pandemic, exacerbated by volcanic eruptions and insufficient access to food aid. Our results suggest the need for the development of strategies and interventions aimed at increasing the resilience of food systems to mitigate the effects of future disasters

CRP 463: University Area Multi-Modal Access Plan June 2016

This study outlines work completed as a part of the CRP 463 senior capstone class outlining a new, comprehensive approach to active transportation on the Cal Poly campus. Led by Dr. William Riggs the project assessed the current conditions, identified opportunities and constraints and then developed conceptual options for a campus active transportation plan. In addition to this process the plan involved completion of a draft Bicycle Friendly University application for the Cal Poly campus (included as a supplemental file) and envisioned conceptual design options for various locations on the campus. Key locations evaluated included the Perimeter Road / University Drive corridor running through campus and the Bella Montana residential campus. The ultimate goal for the plan and these concepts was to expand on proposals from the Cal Poly Masterplan, and provide development templates for future planning and growth that supports multi-modal travel

ΔFlucs: brighter photinus pyralis firefly luciferases identified by surveying consecutive single amino acid deletion mutations in a thermostable variant

The bright bioluminescence catalyzed by Photinus pyralis firefly luciferase (Fluc) enables a vast array of life science research such as bio imaging in live animals and sensitive in vitro diagnostics. The effectiveness of such applications is improved using engineered enzymes that to date have been constructed using amino acid substitutions. We describe ΔFlucs: consecutive single amino acid deletion mutants within six loop structures of the bright and thermostable ×11 Fluc. Deletion mutations are a promising avenue to explore new sequence and functional space and isolate novel mutant phenotypes. However, this method is often overlooked and to date there have been no surveys of the effects of consecutive single amino acid deletions in Fluc. We constructed a large semi-rational ΔFluc library and isolated significantly brighter enzymes after finding ×11 Fluc activity was largely tolerant to deletions. Targeting an “omega-loop” motif (T352-G360) significantly enhanced activity, altered kinetics, reduced Km for D-luciferin, altered emission colors, and altered substrate specificity for redshifted analog DL-infraluciferin. Experimental and in silico analyses suggested remodeling of the Ω-loop impacts on active site hydrophobicity to increase light yields. This work demonstrates the further potential of deletion mutations, which can generate useful Fluc mutants and broaden the palette of the biomedical and biotechnological bioluminescence enzyme toolbox

Methods and results of a search for gravitational waves associated with gamma-ray bursts using the GEO 600, LIGO, and Virgo detectors

In this paper we report on a search for short-duration gravitational wave bursts in the frequency range 64 Hz-1792 Hz associated with gamma-ray bursts (GRBs), using data from GEO 600 and one of the LIGO or Virgo detectors. We introduce the method of a linear search grid to analyze GRB events with large sky localization uncertainties, for example the localizations provided by the Fermi Gamma-ray Burst Monitor (GBM). Coherent searches for gravitational waves (GWs) can be computationally intensive when the GRB sky position is not well localized, due to the corrections required for the difference in arrival time between detectors. Using a linear search grid we are able to reduce the computational cost of the analysis by a factor of O(10) for GBM events. Furthermore, we demonstrate that our analysis pipeline can improve upon the sky localization of GRBs detected by the GBM, if a high-frequency GW signal is observed in coincidence. We use the method of the linear grid in a search for GWs associated with 129 GRBs observed satellite-based gamma-ray experiments between 2006 and 2011. The GRBs in our sample had not been previously analyzed for GW counterparts. A fraction of our GRB events are analyzed using data from GEO 600 while the detector was using squeezed-light states to improve its sensitivity; this is the first search for GWs using data from a squeezed-light interferometric observatory. We find no evidence for GW signals, either with any individual GRB in this sample or with the population as a whole. For each GRB we place lower bounds on the distance to the progenitor, under an assumption of a fixed GW emission energy of 10-2Mc2, with a median exclusion distance of 0.8 Mpc for emission at 500 Hz and 0.3 Mpc at 1 kHz. The reduced computational cost associated with a linear search grid will enable rapid searches for GWs associated with Fermi GBM events once the advanced LIGO and Virgo detectors begin operation. © 2014 American Physical Society

Search for gravitational waves associated with γ-ray bursts detected by the interplanetary network

We present the results of a search for gravitational waves associated with 223 γ-ray bursts (GRBs) detected by the InterPlanetary Network (IPN) in 2005-2010 during LIGO\u27s fifth and sixth science runs and Virgo\u27s first, second, and third science runs. The IPN satellites provide accurate times of the bursts and sky localizations that vary significantly from degree scale to hundreds of square degrees. We search for both a well-modeled binary coalescence signal, the favored progenitor model for short GRBs, and for generic, unmodeled gravitational wave bursts. Both searches use the event time and sky localization to improve the gravitational wave search sensitivity as compared to corresponding all-time, all-sky searches. We find no evidence of a gravitational wave signal associated with any of the IPN GRBs in the sample, nor do we find evidence for a population of weak gravitational wave signals associated with the GRBs. For all IPN-detected GRBs, for which a sufficient duration of quality gravitational wave data are available, we place lower bounds on the distance to the source in accordance with an optimistic assumption of gravitational wave emission energy of 10-2Mc2 at 150 Hz, and find a median of 13 Mpc. For the 27 short-hard GRBs we place 90% confidence exclusion distances to two source models: a binary neutron star coalescence, with a median distance of 12 Mpc, or the coalescence of a neutron star and black hole, with a median distance of 22 Mpc. Finally, we combine this search with previously published results to provide a population statement for GRB searches in first-generation LIGO and Virgo gravitational wave detectors and a resulting examination of prospects for the advanced gravitational wave detectors. © 2014 American Physical Society

Oncological outcomes of visibly complete transurethral resection prior to neoadjuvant chemotherapy for bladder cancer

ABSTRACT Purpose: To evaluate the potential oncologic benefit of a visibly complete transurethral resection of a bladder tumor (TURBT) prior to neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). Materials and Methods: We identified patients who received NAC and RC between 2011-2021. Records were reviewed to assess TURBT completeness. The primary outcome was pathologic downstaging (<ypT2N0), with complete pathologic response (ypT0N0) and survival as secondary endpoints. Logistic regression and Cox proportional hazards models were utilized. Results: We identified 153 patients, including 116 (76%) with a complete TURBT. Sixty-four (42%) achieved <ypT2N0 and 43 (28%) achieved ypT0N0. When comparing those with and without a complete TURBT, there was no significant difference in the proportion with <ypT2N0 (43% vs 38%, P=0.57) or ypT0N0 (28% vs 27%, P=0.87). After median follow-up of 3.6 years (IQR 1.5-5.1), 86 patients died, 37 died from bladder cancer, and 61 had recurrence. We did not observe a statistically significant association of complete TURBT with cancer-specific or recurrence-free survival (p≥0.20), although the hazard of death from any cause was significantly higher among those with incomplete TURBT even after adjusting for ECOG and pathologic T stage, HR 1.77 (95% CI 1.04-3.00, P=.034). Conclusions: A visibly complete TURBT was not associated with pathologic downstaging, cancer-specific or recurrence-free survival following NAC and RC. These data do not support the need for repeat TURBT to achieve a visibly complete resection if NAC and RC are planned

Two Homologous Putative Protein Tyrosine Phosphatases, OsPFA-DSP2 and AtPFA-DSP4, Negatively Regulate the Pathogen Response in Transgenic Plants

Protein phosphatases, together with protein kinases, regulate protein phosphorylation and dephosphorylation, and play critical roles in plant growth and biotic stress responses. However, little is known about the biological functions of plant protein tyrosine dual-specificity phosphatase (PFA-DSP) in biotic stresses. Here, we found that OsPFA-DSP2 was mainly expressed in calli, seedlings, roots, and young panicles, and localized in cytoplasm and nucleus. Ectopic overexpression of OsPFA-DSP2 in rice increased sensitivity to Magnaporthe grisea (M. grisea Z1 strain), inhibited the accumulation of hydrogen peroxide (H2O2) and suppressed the expression of pathogenesis-related (PR) genes after fungal infection. Interestingly, transgenic Arabidopsis plants overexpressing AtPFA-DSP4, which is homologous to OsPFA-DSP2, also exhibited sensitivity to Pseudomonas syringae pv. tomato DC3000 (Pst DC3000), reduced accumulation of H2O2 and decreased photosynthesic capacity after infection compared with Col-0. These results indicate that OsPFA-DSP2 and AtPFA-DSP4 act as negative regulators of the pathogen response in transgenic plants

The Freedom Budget at 45: Functional Finance and Full Employment

Forty-five years ago, the A. Philip Randolph Institute issued The Freedom Budget, in which a program for economic transformation was proposed that included a job guarantee for everyone ready and willing to work, a guaranteed income for those unable to work or those who should not be working, and a living wage to lift the working poor out of poverty. Such policies were supported by a host of scholars, civic leaders, and institutions, including the Rev. Dr. Martin Luther King Jr.; indeed, they provided the cornerstones for King's Poor Peoples' Campaign and economic bill of rights. This paper proposes a New Freedom Budget for full employment based on the principles of functional finance. To counter a major obstacle to such a policy program, the paper includes a primer on three paradigms for understanding government budget deficits and the national debt: the deficit hawk, deficit dove, and functional finance perspectives. Finally, some of the benefits of the job guarantee are outlined, including the ways in which the program may serve as a vehicle for a variety of social policies