ARTICLE | doi:10.20944/preprints202009.0193.v1
Subject: Arts & Humanities, Other Keywords: Science and policy - making; Environmental communication; Pan - Canadian Framework on Clean Growth and Climate Change
Online: 9 September 2020 (03:13:14 CEST)
The science‐policy interface in climate change adaptation became better managed over the past decades. However, the scientists and other knowledge producers, as well as policy makers still need to take bolder steps to more effectively engage with others to apply science and shape up policies. This paper aims to provide practical recommendations, intended to promote conversations between science and policy sectors to address climate change issues. Here, I used two different approaches to synthesize experiences and identify recommendations: a literature review and a case study. The paper stress main findings: (1) The linear communication model is still commonly involved in the science - policy dialogue and proved to be useful to increase the relevance of science and data products to decision makers. (2) When a gap between knowledge producer and knowledge user or decision maker exists, the need for a third party to specialize in bridging the gap become essential. (3) Indigenous people and knowledge must be involved in adaptation policy making based on legitimation local and traditional knowledge, designing the consultation process to broadly engage local and indigenous people, facilitating meaningful dialogues between traditional knowledge and science, and developing initiatives to strengthen skills and capacity of indigenous communities.
ARTICLE | doi:10.20944/preprints201808.0245.v1
Online: 14 August 2018 (05:57:51 CEST)
Our paper examines the place of Pan-Africanism as an educational, political, and cultural movement which had a lasting impact on the on the relationship between liberation and people of African descent, in the continent of Africa and the Diaspora. We also show its evolution, beginning with formerly enslaved Africans in the Americas, to the colonial borders of the 1884 Berlin Conference, and conclude with the independence movements in Africa. For formerly enslaved Africans, Pan-Africanism was an idea that helped them see their commonalities as victims of racism. That is, they realized that they were enslaved because they came from the same continent and shared the same racial heritage. They associated the continent of Africa with freedom. The partitioning of Africa at the Berlin Conference (colonialism) created pseudo-nation states out of what was initially seen as an undivided continent. Pan-Africanism provided an ideology for rallying Africans at home and abroad against colonialism, and the creation of colonial nation-states did not erase the idea of a united Africa. As different African nations gained political independence, they took it upon themselves to support those countries fighting for their independence. The belief, then, was that as long as one African nation was not free, the continent could not be viewed as free. The existence of nation-states did not imply the negation of Pan-Africanism. The political ideas we examine include those of Marcus Garvey, W.E.B. Du Bois, Kwame Nkrumah, and Thabo Mbeki.
ARTICLE | doi:10.20944/preprints202110.0001.v1
Online: 1 October 2021 (08:18:18 CEST)
One of the hallmarks of the Alternative Lengthening of Telomeres (ALT) is the association with Promyelocytic Leukemia (PML) Nuclear Bodies, known as APBs. In the last years, APBs have been described as the main place where telomeric extension occurs in ALT positive cancer cell lines. A different set of proteins have been associated with APBs function, however, the molecular mechanisms behind their assembly, colocalization, and clustering of telomeres, among others, remain unclear. To improve the understanding of APBs in the ALT pathway, we integrated multi-omics analyses to evaluate genomic, transcriptomic and proteomic alterations, and functional interactions of 71 APBs-related genes/proteins in 32 PanCancer Atlas studies from The Cancer Genome Atlas Consortium (TCGA). As a result, we identified 13 key proteins which showed distinctive mutations, interactions, and functional enrichment patterns across all the cancer types and proposed this set of proteins as candidates for future ex vivo and in vivo analyses that will validate these proteins to improve the understanding of the ALT pathway, fill the current research gap about APBs function and their role in ALT, and be considered as potential therapeutic targets for the diagnosis and treatment of ALT positive cancers in the future.
ARTICLE | doi:10.20944/preprints201807.0113.v1
Online: 6 July 2018 (09:37:08 CEST)
Bidirectional gene promoters affect the transcription of two genes, leading to the hypothesis that they should exhibit protection against genetic or epigenetic changes in cancer. Therefore, they provide an excellent opportunity to learn about promoter susceptibility to somatic alteration in tumors. We tested this hypothesis using data from genome-scale DNA methylation (14 cancer types), simple somatic mutation (10 cancer types), and copy number variation profiling (14 cancer types). For DNA methylation, the difference in rank differential methylation between tumor and tumor-adjacent normal matched samples based on promoter type was tested by Wilcoxon rank sum test. Logistic regression was used to compare differences in simple somatic mutations. For copy number alteration, a mixed effects logistic regression model was used. The change in methylation between non-diseased tissues and their tumor counterparts was significantly greater in single compared to bidirectional promoters across all 14 cancer types examined. Similarly, the extent of copy number alteration was greater in single gene compared to bidirectional promoters for all 14 cancer types. Furthermore, among 10 cancer types with available simple somatic mutation data, bidirectional promoters were slightly more susceptible. These results suggest that selective pressures related with specific functional impacts during carcinogenesis drive the susceptibility of promoter regions to somatic alteration.
ARTICLE | doi:10.20944/preprints202108.0563.v1
Subject: Engineering, Civil Engineering Keywords: Iran; Pan Evaporation; Genetic Algorithm; MLP Neural Network; Experimental Relationship
Online: 31 August 2021 (11:20:33 CEST)
Evaporation from surface water plays a key role in water accounting of basins, water resources management, and irrigation systems management, so simulating evaporation with high accuracy is very important. In this study, two methods for simulating pan evaporation under different climatic conditions in Iran were developed. In the first method, six experimental relationships (linear, quadratic, and cubic, with two input combinations) were determined for Iran’s six climate types, inspired by a multilayer perceptron neural network (MLP-NN) neuron and optimized with the genetic algorithm. The best relationship of the six was selected for each climate type, and the results were presented in a three-dimensional graph. In the second method, the best overall relationship obtained in the first method was used as the basic relationship, and climatic correction coefficients were determined for other climate types using the genetic algorithm optimization model. Finally, the accuracy of the two methods was validated using data from 32 synoptic weather stations throughout Iran. For the first method, error tolerance diagrams and statistical coefficients showed that a quadratic experimental relationship performed best under all climatic conditions. To simplify the method, two graphs were created based on the quadratic relationship for the different climate types, with the axes of the graphs showing relative humidity and temperature, and with pan evaporation was drawn as contours. For the second method, the quadratic relationship for semi-dry conditions was selected as the basic relationship. The estimated climatic correction coefficients for other climate types lay between 0.8 and 1 for dry, semi-dry, semi-humid, Mediterranean climates, and between 0.4 and 0.6 for humid and very humid climates, indicating that one single relationship cannot be used to simulate pan evaporation for all climatic conditions in Iran. The validation results confirmed the accuracy of the two methods in simulating pan evaporation under different climatic conditions in Iran.
ARTICLE | doi:10.20944/preprints201907.0258.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: GPR15, pan-cancer, TCGA, cancer immunity, differential gene expression, prognosis, virtual screening
Online: 23 July 2019 (11:15:19 CEST)
G protein-coupled receptor 15 (GPR15, also known as BOB) is an extensively studied orphan GPCR involving HIV infection, colonic inflammation and smoking-related diseases. Recently, GPR15 was deorphanized and its corresponding natural ligand demonstrated an ability of inhibiting cancer cell growth. However, no study reported the potential role of GPR15 in a pan-cancer manner. Using large-scale publicly available data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases, we found that GPR15 expression is significantly lower in colon adenocarcinoma (COAD) than in normal tissues. And among 33 cancer types, GPR15 expression is significantly correlated with the prognoses of COAD, neck squamous carcinoma (HNSC), lung adenocarcinoma (LUAD) positively and stomach adenocarcinoma (STAD) negatively. This study also revealed that commonly upregulated gene set in the high GPR15 expression group (stratified via median) of COAD, HNSC, LUAD and STAD are enriched in immune systems, indicating that GPR15 might be considered as a potential target for cancer immunotherapy. Furthermore, we modelled the 3D structure of GPR15 and conducted the structure-based virtual screening. The top 8 hits compounds were screened and then subjected to molecular dynamics (MD) simulation for stability analysis. Our study provided novel insights into the role of GPR15 in a pan-cancer manner and discovered a potential hit compound for GPR15 antagonists.
ARTICLE | doi:10.20944/preprints202008.0131.v1
Subject: Social Sciences, Political Science Keywords: Pan-Africanism; African Diaspora; human rights; liberation; transformational leadership; civil rights; colonialism; Martin Luther King Jr.; Nelson Mandela
Online: 5 August 2020 (10:48:12 CEST)
The Rev. Martin Luther King Jr. and Nelson Mandela were two of the world's most iconic civil (political) (human) rights advocates and leaders of all time. Both advocated for, and to varying degrees, applied elements of peaceful protests to the achievement of their goals. Both spent time in jail, often concurrently, but eventually forced their respective countries to extend the same rights that white populations had denied Africans and African Americans. For the US, civil rights, voting rights, right to education, housing and housing loans suggested that equality had been achieved, capped in South Africa by the election of Nelson Mandela as the first majority-rule president, and in the US, by Barack Obama’s election to the presidency. Yet the historical over-policing, police mistreatment and more generally, the judicial system’s inordinate ‘targeting’ of African Americans, with egregious cases running from Emmett Till to Rodney King to Walter Scott to Breonna Taylor to George Floyd to Rayshard Brooks and thousands of others shows the danger of such magical thinking. The now-persistent global wave pursuing human rights, civil rights and the right to be treated equally, primarily driven by the loosely-organized Black Lives Matter (BLM) movement, has become the leading voice in pursuit of equality. Riots such as those in LA, protests in Ferguson and everywhere in summer 2020 has ushered new civil rights campaign. In the US and elsewhere, it has morphed to include historical issues such as monuments to colonialism, the US civil war, slavery and slave owners and traders, institutions, companies and people whose wealth and existence has links to slavery. Instructively, the protests persisted even as COVID-19, the hundred-year plague, continues to ravage the world. Lost in the moment is the absence of central leadership and leaders such as MLK or Mandela. Their charisma and effectiveness has been lacking for 50 years. This paper evaluates whether this has led to inconsistent civil and human rights pursuit for equality, or whether perchance, Mandela and MLK were extraordinary, once-in-a-lifetime transformative leaders uniquely selected by history for their time.
REVIEW | doi:10.20944/preprints202102.0058.v1
Subject: Medicine & Pharmacology, Allergology Keywords: pan-antiviral; rocaglates; eIF4A; silvestrol; CR-31-B; zotatifin; translation initiation; coronavirus; COVID-19
Online: 1 February 2021 (15:44:20 CET)
The increase in pandemics caused by RNA viruses of zoonotic origin highlights the urgent need for broad-spectrum antivirals against novel and re-emerging RNA viruses. Broad-spectrum antivirals could be deployed as first-line interventions during an outbreak while virus-specific drugs and vaccines are developed and rolled out. Viruses depend on the host’s protein synthesis machinery for replication. Several natural compounds that target the cellular DEAD-box RNA helicase eIF4A, a key component of the eukaryotic translation initiation complex eIF4F, have emerged as potential broad-spectrum antivirals. Rocaglates, a group of flavaglines of plant origin that clamp mRNAs with highly structured 5’UTRs onto the surface of eIF4A through specific stacking interactions, exhibit the largest selectivity and potential therapeutic indices among all known eIF4A inhibitors. Their unique mechanism of action limits the inhibitory effect of rocaglates to the translation of eIF4A-dependent viral mRNAs and a minor fraction of host mRNAs exhibiting stable RNA secondary structures and/or polypurine sequence stretches in their 5´UTRs, resulting in minimal potential toxic side effects. Maintaining a favorable safety profile while inducing efficient inhibition of a broad-spectrum of RNA viruses makes rocaglates into primary candidates for further development as pan-antiviral therapeutics.
ARTICLE | doi:10.20944/preprints201808.0036.v1
Subject: Life Sciences, Microbiology Keywords: ESKAPE-bacteria; persistence; resistance; Intrinsic/Acquired/ Multidrug (MDR) and Pan – Resistance; genetic background; experimental evolution; collateral sensitivity; agrocin
Online: 2 August 2018 (06:29:07 CEST)
The challenge posed by multi-drug resistance (MDR) of pathogenic organisms, spectacularly manifested in the 6 “ESKAPE” bacterium (two Gram-positive, four Gram-negative) species, should invoke new comprehensive strategies, and needs cooperation of scientists with medical, veterinary and natural science background. This review is aimed at informing newcomers, coming from the field of biology and genetics, about problems related to rapidly emerging, new multi-drug resistant, pathogenic, bacteria. Unlike persistence, the antibiotic resistance is inherited. A functioning “resistance gene” makes a susceptible organism resistant to a given antibiotic, encoding for polypeptides capable of acting either as decomposing enzymes, or acting as trans-membrane pumps, or membrane structure components capable of modifying the permeability implementing a «by pass» mechanism enabling the antibiotic molecule to reach its cellular target(s). A functioning “sensitivity gene” encode for a polypeptide, capable (directly or indirectly) of transferring toxic molecules into target cells, or of metabolizing non-transferable to transferable, or non-toxic molecules to toxic derivatives. A gene of a normal function could act as a “sensitivity” gene in the presence of antibiotics of chemical structures similar to the natural substrate of the gene product, (enzyme or binding/ trans-membrane protein). The Agrocin 84 story is a good example. Multi-drug resistance is a phenotypic consequence of the sequential accumulation of mutations, and/or up-take of plasmids or genomic islands carrying resistance genes from the environment via horizontal gene transfer, mediated by conjugative plasmid or bacteriophage carrying mobile genetic elements. Both multi-drug resistance and collateral sensitivity are evolutionary products. Some revealed evolutionary process and their Lamarckian and Darwinian interpretations are discussed. Toolkits of comparative full-genome sequencing, genomics, experimental evolution and population genetics may provide perspectives for overcoming the invincibility of multi-drug panresistance. The status of some recently emerging pathogenic bacterium species with zoonic features and of veterinary background is also discussed.
ARTICLE | doi:10.20944/preprints202111.0266.v1
Subject: Engineering, Biomedical & Chemical Engineering Keywords: Pan-Cancer; somatic point mutations; cancer subtyping; biomarker discovery; driver genes; per-sonalized medicine; health data analytics
Online: 15 November 2021 (13:51:33 CET)
The advent of high throughput sequencing has enabled researchers to systematically evaluate the genetic variations in cancer, resulting in identifying many cancer-associated genes. Although cancers in the same tissue are widely categorized in the same group, they demonstrate many differences concerning their mutational profiles. Hence there is no “silver bullet” for the treatment of a cancer type. This reveals the importance of developing a pipeline to identify cancer-associated genes accurately and re-classify patients with similar mutational profiles. Classification of cancer patients with similar mutational profiles may help discover subtypes of cancer patients who might benefit from specific treatment types. In this study, we propose a new machine learning pipeline to identify protein-coding genes mutated in a significant portion of samples to identify cancer subtypes. We applied our pipeline to 12270 samples collected from the International Cancer Genome Consortium (ICGC), covering 19 cancer types. Here we identified 17 different cancer subtypes. Comprehensive phenotypic and genotypic analysis indicates distinguishable properties, including unique cancer-related signaling pathways, in which, for most of them, targeted treatment options are currently available. This new subtyping approach offers a novel opportunity for cancer drug development based on the mutational profile of patients. We also comprehensive study the causes of mutations among samples in each subtype by mining the mutational signatures, which provides important insight into their active molecular mechanisms. Some of the pathways we identified in most subtypes, including the cell cycle and the Axon guidance pathways, are frequently observed in cancer disease. Interestingly, we also identified several mutated genes and different rates of mutation in multiple cancer subtypes. In addition, our study on “gene-motif” suggests the importance of considering both the context of the mutations and mutational processes in identifying cancer-associated genes. The source codes for our proposed clustering pipeline and analysis are publicly available at: https://github.com/bcb-sut/Pan-Cancer.
ARTICLE | doi:10.20944/preprints201805.0149.v1
Subject: Engineering, Electrical & Electronic Engineering Keywords: Atmospheric path-radiance; change analysis; detail injection modeling; haze; data fusion; normalized differential vegetation index (NDVI); pan-sharpening; radiative transfer; vegetation.
Online: 9 May 2018 (15:11:25 CEST)
Whenever vegetated areas are monitored over time, phenological changes in land cover should be decoupled from changes in acquisition conditions, like atmospheric components, sun and satellite heights, and imaging instrument. This especially holds when the multispectral (MS) bands are sharpened for spatial resolution enhancement by means of a panchromatic (Pan) image of higher resolution, a process referred to as pansharpening. In this paper, we provide evidence that pansharpening of visible/near-infrared (VNIR) bands takes advantage from a correction of the path radiance term introduced by the atmosphere, during the fusion process. This holds whenever the fusion mechanism emulates the radiative transfer model ruling the acquisition of the Earth’s surface from space, that is, for methods exploiting a multiplicative, or contrast-based, injection model of spatial details extracted from the panchromatic (Pan) image into the interpolated multispectral (MS) bands. The path radiance should be estimated and subtracted from each band before the product by Pan is accomplished. Both empirical and model-based estimation techniques of MS path radiances are compared within the framework of optimized algorithms. Simulations carried out on two GeoEye-1 observations of the same agricultural landscape at different dates highlight that the de-hazing of MS before fusion is beneficial for an accurate detection of seasonal changes in the scene, as measured by the normalized differential vegetation index (NDVI).