Ongoing colonization of the environment and natural resources has negatively impacted environmental heritage rights in many parts of the world, particularly Indigenous environmental rights and their ...relationships with the environment. For many Indigenous communities, the history of colonialism became a history of dispossession for Indigenous peoples, their land, water, traditional knowledge, and practices. This paper addresses the ongoing environmental heritage conflict between the Cree First Nation communities’ traditional environmental heritage practices and developmental energy projects in Saskatchewan, Canada. Drawing from a relational research framework, we (Cree First Nation Knowledge Keeper and settler scholar of color) shared our learning reflections from Cree First Nation communities on how energy projects (particularly pipeline leaks) have negatively impacted Indigenous land, water, and traditional heritage and practices. In this paper, we focus our learnings from the Cree First Nation communities on the following questions: Why and how do developmental projects neglect Indigenous heritage rights, particularly environmental heritage rights? What can be or should be done about it? What are our responsibilities as researchers and educators? In this study, we learned about traditional-knowledge-based consultation and solutions to the ongoing challenges of incorporating Indigenous interests into environmental heritage to foster Indigenous environmental heritage rights. We also highlight how Indigenous perspectives on their environmental heritage rights are interconnected with Sustainable Development Goals (SDGs) from our learning reflections, particularly Goal 3, Good Health and Wellbeing, Goal 10, Reduced Inequalities, Goal 13, Climate Action, Goal 15, Life on Land, and Goal 16, Peace, Justice, and Strong Institutions.
Leukemia phenotypes vary with age of onset. Delineating mechanisms of age specificity in leukemia could improve disease models and uncover new therapeutic approaches. Here, we used heterochronic ...transplantation of leukemia driven by
/
translocations to investigate the contribution of the age of the hematopoietic microenvironment to age-specific leukemia phenotypes. When driven by
, leukemia cells in the adult microenvironment sustained a myeloid phenotype, whereas the neonatal microenvironment supported genesis of mixed early B cell/myeloid leukemia. In
leukemia, the neonatal microenvironment potentiated B-lymphoid differentiation compared with the adult. Ccl5 elaborated from adult marrow stroma inhibited B-lymphoid differentiation of leukemia cells, illuminating a mechanism of age-specific lineage commitment. Our study illustrates the contribution of the developmental stage of the hematopoietic microenvironment in defining the age specificity of leukemia.
Microscopy and antigen detecting rapid diagnostic tests are the diagnostic tests of choice in management of clinical malaria. However, due to their limitations, the need to utilize more sensitive ...methods such as real-time PCR (qPCR) is evident as more studies are now utilizing molecular methods in detection of malaria. Some of the challenges that continue to limit the widespread utilization of qPCR include lack of assay standardization, assay variability, risk of contamination, and the need for cold-chain. Lyophilization of molecular assays can overcome some of these limitations and potentially enable widespread qPCR utilization.
A recently published multiplex malaria qPCR assay was lyophilized by freezing drying into Sample-Ready™ format (MMSR). MMSR assay contained all the required reagents for qPCR including primers and probes, requiring only the addition of water and sample to perform qPCR. The performance of the MMSR assay was compared to the non-freeze dried, "wet" assay. Stability studies were done by maintaining the MMSR assays at four different ambient temperatures of 4°C, room temperature (RT), 37°C and 42°C over a period of 42 days, tested at seven-day intervals. Plasmodium falciparum and Plasmodium vivax DNAs were used for analysis of the MMSR assay either as single or mixed parasites, at two different concentrations. The CT values and the standard deviations (SD) were used in the analysis of the assay performance.
The limit of detection for the MMSR assay was 0.244 parasites/μL for Plasmodium spp. (PLU) and P. falciparum (FAL) assay targets compared to "wet" assay which was 0.39 and 3.13 parasites/μL for PLU and FAL assay targets, respectively. The MMSR assay performed with high efficiencies similar to those of the "wet" assay and was stable at 37°C for 42 days, with estimated shelf-life of 5 months. When used to analyse field clinical samples, MMSR assay performed with 100% sensitivity and specificity compared to the "wet" assay.
The MMSR assay has the same robust performance characteristics as the "wet" assay and is highly stable. Availability of MMSR assay allows flexibility and provides an option in choosing assay for malaria diagnostics depending on the application, needs and budget.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The tail of the bacteriophage P22 is composed of multiple protein components and integrates various biological functions that are crucial to the assembly and infection of the phage. The ...three‐dimensional structure of the P22 tail machine determined by electron cryo‐microscopy and image reconstruction reveals how the five types of polypeptides present as 51 subunits are organized into this molecular machine through twelve‐, six‐ and three‐fold symmetry, and provides insights into molecular events during host cell attachment and phage DNA translocation.
How did ordinary people experience Japan's modern transformation? What role did people in local areas play in the making of modern Japan? How do studies of local politics help explain national ...events?The dominant account of modern Japanese history focuses on the nation-building that brought Japan into the modern world. After centuries of isolation, American warships forced Japan to open its doors to the West and a group of tough new leaders transformed the country into one of the great military and economic powers of the world. But different perspectives need to be examined. Alternative Narratives introduces other actors, other places and other dimensions of social and political activity in an attempt to construct a broader and more complex account of modern Japanese history.Focusing on the initial years of Japan's modern transformation, from the 1850s to the 1890s, Steele explores responses of commoners to the arrival of American warships in 1853; the growth of popular political consciousness; reactions of the residents of Edo in 1868 on the deposition of the shogun; responses of the village elite to the fall of the old regime; and established frameworks of historical narration - including American attempts to understand Japan's 1868 civil war.The author draws upon a wealth of documents, including broadsheets, woodblock prints, political cartoons and local campaign literature, as well as more conventional material in an endeavour to find new and different ways to examine the past. This book forms an important resource to students of Japanese history and culture while simultaneously appealing to scholars interested in the general problem of history and history-writing.
This paper examines Indigenous perspectives on energy sustainabilities. We as Indigenous Elders and non-Indigenous scholars collectively explore how pipeline leaks that cost several Indigenous ...communities of the Treaty 6 region (known as western Canada). While the pipeline project has brought income to some, and wealth to the few, its impact on the environment and on the lives of many Indigenous groups is profoundly concerning. Indigenous communities are particularly vulnerable to pipeline leaks, yet have limited capacity to mitigate them as compared to larger urban centers. Using an Indigenist research framework, we used deep listening, traditional stories, reflective journals, cultural camps, and collective stories. We followed traditional protocols, continuous forms of consent, respect, and honour Indigenous Elders and Knowledge-keepers’ stories. We learned about community Elders, Knowledge-keepers, and leaders’ suggestions on how strategic decisions need to be made about pipeline leaks management and energy sustainabilities. The purpose of this paper is to provide Indigenous communities, particularly those communities of western Canada, with new community-led guidelines that can help them make strategic choices about pipeline leaks management to enhance their resiliency to energy. In this paper, we highlighted community suggestions on how to flip the traditional approach of fitting Indigenous ways of knowing into the Canadian legal structures by starting with Indigenous ways of knowing about the relationships of Indigenous people with land, water, and energy together with the impacts of the energy. We hope this paper may assist policy makers and Indigenous communities in sustainable energy policy development and provide a structured, transparent, and participatory decision support tool to government and communities to guide future energy management planning initiatives.
•Identify community-led consultation practices for energy management.•Develop a community-led energy resiliency guideline.•Create risk evaluation framework for addressing pipeline leaks and energy management.•Explore community-led solutions anchored in sustainable energy management politics.•Support Indigenous communities’ and organizations’ attempts to negotiate.
In this study, we analyzed annual production data from 100 000 photovoltaic systems as well as comments relating to their performance and maintenance. Our analysis revealed that 80% to 90% of all ...systems performed within 10% of the predicted production or better. Also, 56% of the systems were still performing above P50 or the median at 5 years. However, a small but significant tail of about 7000 systems perform below P90 expectations. In general, residential systems have a lower rate of failure than utility or commercial systems. Despite higher rates of component failures, utility systems lose less power than residential or commercial systems. This outcome is likely due to closer monitoring and better operations and maintenance practices. Inverters are still the components that reportedly fail most often (4%‐6%), but other failures such as unspecified repair and meters cause more production loss. Reported module failures are relatively rare (0.2%) and are within the range of historical values. Installation quality affects performance and safety as indicated by data showing connector, wiring, breaker, and fuse failures due to undersizing, electrical design, and improper connection. Lastly, early detection of degradation and proactive response resulted in less impact on production than reactive, unplanned repairs.
In this study, we analyzed annual production data from 100 000 photovoltaic systems as well as comments relating to their performance and maintenance. Inverters are the components that fail most often (4%‐6%), but other failures such as unspecified repair and meters cause more production loss with module failures being relatively rare (0.2%). Installation quality affects performance and safety as indicated by data showing connector, wiring, breaker, and fuse failures.
Abstract only
Introduction:
Conduction system pacing (CSP) is an increasingly used physiologic pacing modality by either His-bundle pacing (HBP) or left-bundle area pacing (LBAP). However, operators ...new to this technique may hesitate to implement CSP. We describe a single operator's experience (learning curve, clinical outcomes) with CSP from 07/2016-05/2022.
Methods:
Retrospective analysis of all 3830 Medtronic SelectSecure leads implanted by one operator at an academic institution. Patient characteristics, procedure times, ECG findings, pacing parameters, and clinical outcomes were analyzed.
Results:
A
total
of 140 CSP cases (Medtronic 3830 lead) were attempted over 70 months (78 HBP, 62 LBAP).
Implant frequency
(year → # of cases): 2016 → 3; 2017 → 5; 2018 → 24; 2019 → 25; 2020 → 36; 2021 → 35; 2022 → 12. The last HBP lead was implanted in March 2021; the 1st LBAP lead was implanted in December 2019. There were 23
unsuccessful attempts
to achieve CSP at initial implantation (18 in the 1st 34%, mainly HBP cases; 5 in the last 92 cases) and 5
revisions
(all HBP, see figure
). Procedure times
shortened after the 1st 25 procedures for both HBP (158 to 132 mins, P=0.028) and LBAP (174 to 133 mins, P=0.002). Mean
follow-up:
HBP=558.2 days and LBAP=109 days. Ten patients (4 HBP, 6 LBAP) were lost to follow up. LBAP leads showed significantly better capture
thresholds
compared to HBP at implant and follow-up, although QRS narrowing, LV activation times, and improvement in LV function were not significantly different (see table).
Conclusion:
LBAP is easier to learn and has fewer failure rates as compared to HBP. Procedure times improve with experience within 25 cases. Majority of failed attempts were in the first third of cases, and all but one were in the HBP group.
Operators new to CSP should forego HBP and employ LBAP.
LBAP provides similar reductions in QRS duration, LV activation times, and LVEF improvement as compared to HBP, but with lower failure/revision rates and superior long-term pacing thresholds.
LIN28 is an RNA-binding protein that regulates the maturation of the let-7 family of microRNAs by bipartite interactions with let-7 precursors through its two distinct cold shock and zinc-knuckle ...domains. Through inhibition of let-7 biogenesis, LIN28 functions as a pluripotency factor, as well as a driver of tumorigenesis. Here, we report a fluorescence polarization assay to identify small-molecule inhibitors for both domains of LIN28 involved in let-7 interactions. Of 101,017 compounds screened, six inhibit LIN28:let-7 binding and impair LIN28-mediated let-7 oligouridylation. Upon further characterization, we demonstrate that the LIN28 inhibitor TPEN destabilizes the zinc-knuckle domain of LIN28, while LI71 binds the cold shock domain to suppress LIN28’s activity against let-7 in leukemia cells and embryonic stem cells. Our results demonstrate selective pharmacologic inhibition of individual domains of LIN28 and provide a foundation for therapeutic inhibition of the let-7 biogenesis pathway in LIN28-driven diseases.
Display omitted
•A screening pipeline developed to identify inhibitors targeting both domains of LIN28•Six compounds effectively inhibit LIN28-mediated oligouridylation of let-7•TPEN destabilizes the zinc-knuckle domain, while LI71 modulates the cold shock domain•MNA represents a minimal scaffold as a LIN28 inhibitor targeting the cold shock domain
LIN28 is an oncogenic protein that promotes transformation in malignancy by suppressing the maturation of let-7 microRNAs. Wang et al. developed a high-throughput screening strategy and identified inhibitors of LIN28 that restore mature let-7 levels.
Background
Conduction system pacing (CSP) is increasingly utilized to prevent and correct dyssynchrony. Barriers to CSP adoption include limited training, methodologic variability, laboratory slot ...allocation, and few data on learning curves. We report learning curves/clinical outcomes from a single experienced electrophysiologist who was new to CSP, and share gained insights.
Methods
Retrospective analysis of all patients who underwent attempted CSP implantation (2016–2023). Patient characteristics, ECGs, echocardiograms, fluoroscopy/procedure times, lead data were recorded at implant and follow‐up.
Results
CSP leads were implanted successfully in 167/191(87.4%) patients with a follow‐up of 278 ± 378 days. His‐bundle pacing (HBP = 59) and left‐bundle‐area pacing (LBAP = 108) had similar procedure/fluoroscopy times, QRS duration decreases, and ejection fraction improvements (all p > NS). Eight HBP lead revisions were required for high capture thresholds LBAP demonstrated lower pacing thresholds, higher lead impedances, and greater R‐wave amplitudes at implant and follow‐up. After 25 HBP cases, implant pacing thresholds, fluoroscopy, procedural times did not decrease. After 25 LBAP cases, there were significant decreases in all these parameters (p < 0.05). A separate analysis in LBAP patients with recorded Purkinje signals showed no differences in paced ECG characteristics between patients with pre‐ QRS Purkinje signals versus patients with Purkinje signals post‐QRS onset.
Conclusions
Experienced implanters who are new to CSP can achieve steady‐state procedural/fluoroscopy times after a learning curve of 25 implants. LBAP showed lower capture thresholds and higher success rates. Adequate depth of lead deployment (as determined by published parameters) does not require Purkinje potential to be pre‐QRS. Operators new to CSP.can forego HBP and directly implement LBAP.
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