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Although it is well known that humans substantially altered the Malagasy ecosystems, the timing of the human arrival as well as the extension of their environmental impact is yet not well understood. This research aims to study the influence of early human impact and climate change on rainforests and wildlife in northern Madagascar during the past millennia. Results obtained from the lake sediment in a montane environment showed significant changes in vegetation within the lake catchment associated with a major drought that started approximately 1100 years ago. Human impact, revealed by fires, began at roughly the same time and occurred outside the lake catchment. Although this does not dismiss the impacts that humans had at a regional scale, this result demonstrates that the late Holocene natural drought also significantly impacted the ecosystems independently of anthropogenic activities. At a regional scale, a review of species demographic history revealed a substantial number of population bottlenecks during the last millennia, probably resulting from this combination of human-related impact and natural climate changes. This research highlights the importance of a multi-site and multi-proxy comparison for deciphering the nature and succession of environmental changes.
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Background: Discoveries of new species often depend on one or a few specimens, leading to delays as researchers wait for additional context, sometimes for decades. There is currently little professional incentive for a single expert to publish a stand-alone species description. Additionally, while many journals accept taxonomic descriptions, even specialist journals expect insights beyond the descriptive work itself. The combination of these factors exacerbates the issue that only a small fraction of marine species are known and new discoveries are described at a slow pace, while they face increasing threats from accelerating global change. To tackle this challenge, this first compilation of Ocean Species Discoveries (OSD) presents a new collaborative framework to accelerate the description and naming of marine invertebrate taxa that can be extended across all phyla. Through a mode of publication that can be speedy, taxonomy-focused and generate higher citation rates, OSD aims to create an attractive home for single species descriptions. This Senckenberg Ocean Species Alliance (SOSA) approach emphasises thorough, but compact species descriptions and diagnoses, with supporting illustrations and with molecular data when available. Even basic species descriptions carry key data for distributions and ecological interactions (e.g., host-parasite relationships) besides universally valid species names; these are essential for downstream uses, such as conservation assessments and communicating biodiversity to the broader public. New information: This paper presents thirteen marine invertebrate taxa, comprising one new genus, eleven new species and one re-description and reinstatement, covering wide taxonomic, geographic, bathymetric and ecological ranges. The taxa addressed herein span three phyla (Mollusca, Arthropoda, Echinodermata), five classes, eight orders and twelve families. Apart from the new genus, an updated generic diagnosis is provided for four other genera. The newly-described species of the phylum Mollusca are Placiphorellamethanophila Voncina, sp. nov. (Polyplacophora, Mopaliidae), Lepetodrilusmarianae Chen, Watanabe & Tsuda, sp. nov. (Gastropoda, Lepetodrilidae), Shinkailepasgigas Chen, Watanabe & Tsuda, sp. nov. (Gastropoda, Phenacolepadidae) and Lyonsiellaillaesa Machado & Sigwart, sp. nov. (Bivalvia, Lyonsiellidae). The new taxa of the phylum Arthropoda are all members of the subphylum Crustacea: Lepechinellanaces Lörz & Engel, sp. nov. (Amphipoda, Lepechinellidae), Cuniculomaeragrata Tandberg & Jazdzewska, gen. et sp. nov. (Amphipoda, Maeridae), Pseudionellapumulaensis Williams & Landschoff, sp. nov. (Isopoda, Bopyridae), Mastigoniscusminimus Wenz, Knauber & Riehl, sp. nov. (Isopoda, Haploniscidae), Macrostylispapandreas Jonannsen, Riehl & Brandt, sp. nov. (Isopoda, Macrostylidae), Austroniscusindobathyasellus Kaiser, Kniesz & Kihara, sp. nov. (Isopoda, Nannoniscidae) and Apseudopsisdaria Esquete & Tato, sp. nov. (Tanaidacea, Apseudidae). In the phylum Echinodermata, the reinstated species is Psychropotesbuglossa E. Perrier, 1886 (Holothuroidea, Psychropotidae).The study areas span the North and Central Atlantic Ocean, the Indian Ocean and the North, East and West Pacific Ocean and depths from 5.2 m to 7081 m. Specimens of eleven free-living and one parasite species were collected from habitats ranging from an estuary to deep-sea trenches. The species were illustrated with photographs, line drawings, micro-computed tomography, confocal laser scanning microscopy and scanning electron microscopy images. Molecular data are included for nine species and four species include a molecular diagnosis in addition to their morphological diagnosis.The five new geographic and bathymetric distribution records comprise Lepechinellanaces Lörz & Engel, sp. nov., Cuniculomaeragrata Tandberg & Jazdzewska, sp. nov., Pseudionellapumulaensis Williams & Landschoff, sp. nov., Austroniscusindobathyasellus Kaiser, Kniesz & Kihara, sp. nov. and Psychropotesbuglossa E. Perrier, 1886, with the novelty spanning from the species to the family level. The new parasite record is Pseudionellapumulaensis Williams & Landschoff, sp. nov., found in association with the hermit crab Pagurusfraserorum Landschoff & Komai, 2018.
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The island of Nias/Indonesia shows an extremely reduced genetic diversity indicating a strong founder effect. As a consequence, the prevalence of some disease genes should significantly differ among populations depending on the gene pool passed on to the founder population and their successive expansion as it has already been documented for several monogenic diseases. Results of the current study based on routine laboratory blood examination give rise to the notion that this might also hold true for polygenic disorders. We observed very high prevalence of hyperglycemia (non-fasting glucose above 200 mg/dL in 14 % Nias population compared to 1.5 % in the population of the neighboring island of Sumatra) accompanied by hypertriglyceridemia, high non-HDL-cholesterol, and low HDL-cholesterol levels. These findings suggest that the Nias population may be disproportionally affected by prediabetes and type 2 diabetes mellitus. By contrast, laboratory parameters potentially indicative of other polygenic disorders such as total plasma cholesterol, electrolytes, creatinine, urea, and uric acid were comparable between the inhabitants of Nias and Sumatra islands. To our knowledge this is the first study suggesting that the extremely strong genetic bottleneck seen in the Nias population translates into the widespread metabolic disease with potentially deleterious influence on public health.
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Demographic history and mutational load are of paramount importance for the adaptation of the endangered species. However, the effects of population evolutionary history and genetic load on the adaptive potential in endangered conifers remain unclear. Here, using population transcriptome sequencing, whole chloroplast genomes and mitochondrial DNA markers, combined with niche analysis, we determined the demographic history and mutational load for three threatened whitebark pines having different endangered statuses, Pinus bungeana, P. gerardiana and P. squamata. Demographic inference indicated that severe bottlenecks occurred in all three pines at different times, coinciding with periods of major climate and geological changes; in contrast, while P. bungeana experienced a recent population expansion, P. gerardiana and P. squamata maintained small population sizes after bottlenecking. Abundant homozygous-derived variants accumulated in the three pines, particularly in P. squamata, while the species with most heterozygous variants was P. gerardiana. Abundant moderately and few highly deleterious variants accumulated in the pine species that have experienced the most severe demographic bottlenecks (P. gerardiana and P. squamata), most likely because of purging effects. Finally, niche modeling showed that the distribution of P. bungeana might experience a significant expansion in the future, and the species' identified genetic clusters are also supported by differences in the ecological niche. The integration of genomic, demographic and niche data has allowed us to prove that the three threatened pines have contrasting patterns of demographic history and mutational load, which may have important implications in their adaptive potential and thus are also key for informing conservation planning.
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Understanding the dynamics of population recovery in threatened species requires robust longitudinal monitoring datasets. However, evidence-based decision-making is often impeded by variable data collection approaches, necessitating critical evaluation of restricted available baselines. The Hainan gibbon, the world's rarest primate, had possibly declined to only seven or eight individuals in 1978 at Bawangling National Nature Reserve but has experienced subsequent population growth. Past population estimates lack detailed reporting of survey effort, and multiple conflicting estimates are available, hindering assessment of gibbon recovery. We investigated all reported estimates of Bawangling gibbon population size from 1978 to 2022, to evaluate the biological signal of population trends and the extent to which noise associated with varying survey effort, reporting and estimation may mask or misrepresent any underlying signal. This longitudinal dataset demonstrates that the Bawangling population experienced a series of bottlenecks and recoveries, with three successive periods of growth interspersed by population crashes (1978-1989, 1989-2000 and 2000-2022). The rate of gibbon population recovery was progressively slower over time in each successive period of growth, and this potential decline in recovery rate following serial bottlenecks suggests that additional management strategies may be required alongside "nature-based solutions" for this species. However, population viability analysis suggests the 1978 founder population is unlikely to have been as low as seven individuals, raising concerns for interpreting reported historical population counts and understanding the dynamics of the species' recovery. We caution against overinterpreting potential signals within "messy" conservation datasets, and we emphasise the crucial importance of standardised replicable survey methods and transparent reporting of data and effort in all future surveys of Hainan gibbons and other highly threatened species.
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Barley is one of the founder crops of the Neolithic transition in West Asia. While recent advances in genomics have provided a rather detailed picture of barley domestication, there are contradictory views on how the domestication process affected genetic diversity. We set out to revisit this question by integrating public DNA sequencing data from ancient barley and wide collections of extant wild and domesticated accessions. Using two previously overlooked approaches - analyses of chloroplast genomes and genome-wide proportions of private variants - we found that the barley cultivated six millennia ago was genetically unique and more diverse when compared to extant landraces and cultivars. Moreover, the chloroplast genomes revealed a link between the ancient barley, an obscure wild genotype from north-eastern Libya, and a distinct population of barley cultivated in Ethiopia/Eritrea. Based on these results, we hypothesize past existence of a wider North African population that included both wild and cultivated types and suffered from genetic erosion in the past six millennia, likely due to a rapid desertification that ended the Holocene African humid period. Besides providing clues about the origin of Ethiopian landraces, the hypothesis explains the post-domestication loss of diversity observed in barley. Analyses of additional samples will be necessary to resolve the history of African barley and its contribution to the extant cultivated gene pool.
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The significance of the ethical review process in human-based research undertakings cannot be overemphasized as it is necessary to uphold ethical standards and protect participants. However, the review process per se can act as a bottleneck, potentially hindering research progress and leading to academic dishonesty. The present work explores the benefits and challenges of ethical review, emphasizing issues like intellectual theft, forced authorship, and the stifling of independent researchers. Proposed solutions include leveraging previously approved designs, empowering experienced professors for clearance, establishing panels of researchers, creating voluntary ethical approval offices, utilizing private consultancy offices, and establishing a transnational ethical clearance authority. In conclusion, this work stresses the importance of finding mechanisms to streamline the ethical review process while maintaining ethical standards to foster integrity in research and combat academic dishonesty.
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Ética em Pesquisa , Pesquisadores , Humanos , Pesquisadores/ética , Autoria/normas , Pesquisa Biomédica/ética , Pesquisa Biomédica/normas , Revisão Ética , Má Conduta Científica/éticaRESUMO
The Seychelles magpie-robin's (SMR) five island populations exhibit some of the lowest recorded levels of genetic diversity among endangered birds, and high levels of inbreeding. These populations collapsed during the 20th century, and the species was listed as Critically Endangered in the IUCN Red List in 1994. An assisted translocation-for-recovery program initiated in the 1990s increased the number of mature individuals, resulting in its downlisting to Endangered in 2005. Here, we explore the temporal genomic erosion of the SMR based on a dataset of 201 re-sequenced whole genomes that span the past ~150 years. Our sample set includes individuals that predate the bottleneck by up to 100 years, as well as individuals from contemporary populations established during the species recovery program. Despite the SMR's recent demographic recovery, our data reveal a marked increase in both the genetic load and realized load in the extant populations when compared to the historical samples. Conservation management may have reduced the intensity of selection by increasing juvenile survival and relaxing intraspecific competition between individuals, resulting in the accumulation of loss-of-function mutations (i.e. severely deleterious variants) in the rapidly recovering population. In addition, we found a 3-fold decrease in genetic diversity between temporal samples. While the low genetic diversity in modern populations may limit the species' adaptability to future environmental changes, future conservation efforts (including IUCN assessments) may also need to assess the threats posed by their high genetic load. Our computer simulations highlight the value of translocations for genetic rescue and show how this could halt genomic erosion in threatened species such as the SMR.
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Recently, Graph Neural Networks (GNNs) have gained widespread application in automatic brain network classification tasks, owing to their ability to directly capture crucial information in non-Euclidean structures. However, two primary challenges persist in this domain. First, within the realm of clinical neuro-medicine, signals from cerebral regions are inevitably contaminated with noise stemming from physiological or external factors. The construction of brain networks heavily relies on set thresholds and feature information within brain regions, making it susceptible to the incorporation of such noises into the brain topology. Additionally, the static nature of the artificially constructed brain network's adjacent structure restricts real-time changes in brain topology. Second, mainstream GNN-based approaches tend to focus solely on capturing information interactions of nearest neighbor nodes, overlooking high-order topology features. In response to these challenges, we propose an adaptive unsupervised Spatial-Temporal Dynamic Hypergraph Information Bottleneck (ST-DHIB) framework for dynamically optimizing brain networks. Specifically, adopting an information theory perspective, Graph Information Bottleneck (GIB) is employed for purifying graph structure, and dynamically updating the processed input brain signals. From a graph theory standpoint, we utilize the designed Hypergraph Neural Network (HGNN) and Bi-LSTM to capture higher-order spatial-temporal context associations among brain channels. Comprehensive patient-specific and cross-patient experiments have been conducted on two available datasets. The results demonstrate the advancement and generalization of the proposed framework.
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Encéfalo , Redes Neurais de Computação , Humanos , Encéfalo/fisiologia , Rede Nervosa/fisiologia , Teoria da InformaçãoRESUMO
Accurate histopathological subtype prediction is clinically significant for cancer diagnosis and tumor microenvironment analysis. However, achieving accurate histopathological subtype prediction is a challenging task due to (1) instance-level discrimination of histopathological images, (2) low inter-class and large intra-class variances among histopathological images in their shape and chromatin texture, and (3) heterogeneous feature distribution over different images. In this paper, we formulate subtype prediction as fine-grained representation learning and propose a novel multi-instance selective transformer (MIST) framework, effectively achieving accurate histopathological subtype prediction. The proposed MIST designs an effective selective self-attention mechanism with multi-instance learning (MIL) and vision transformer (ViT) to adaptive identify informative instances for fine-grained representation. Innovatively, the MIST entrusts each instance with different contributions to the bag representation based on its interactions with instances and bags. Specifically, a SiT module with selective multi-head self-attention (S-MSA) is well-designed to identify the representative instances by modeling the instance-to-instance interactions. On the contrary, a MIFD module with the information bottleneck is proposed to learn the discriminative fine-grained representation for histopathological images by modeling instance-to-bag interactions with the selected instances. Substantial experiments on five clinical benchmarks demonstrate that the MIST achieves accurate histopathological subtype prediction and obtains state-of-the-art performance with an accuracy of 0.936. The MIST shows great potential to handle fine-grained medical image analysis, such as histopathological subtype prediction in clinical applications.
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Achieving commercially significant yields of recombinant proteins in Bacillus subtilis requires the optimization of its protein production pathway, including transcription, translation, folding, and secretion. Therefore, in this study, our aim was to maximize the secretion of a reporter α-amylase by overcoming potential bottlenecks within the secretion process one by one, using a clustered regularly interspaced short palindromic repeat-Cas9 (CRISPR-Cas9) system. The strength of single and tandem promoters was evaluated by measuring the relative α-amylase activity of AmyQ integrated into the B. subtilis chromosome. Once a suitable promoter was selected, the expression levels of amyQ were upregulated through the iterative integration of up to six gene copies, thus boosting the α-amylase activity 20.9-fold in comparison with the strain harboring a single amyQ gene copy. Next, α-amylase secretion was further improved to a 26.4-fold increase through the overexpression of the extracellular chaperone PrsA and the signal peptide peptidase SppA. When the final expression strain was cultivated in a 3 L fermentor for 90 h, the AmyQ production was enhanced 57.9-fold. The proposed strategy allows for the development of robust marker-free plasmid-less super-secreting B. subtilis strains with industrial relevance.
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Bacillus subtilis , Proteínas de Bactérias , Sistemas CRISPR-Cas , alfa-Amilases , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , alfa-Amilases/genética , alfa-Amilases/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Via Secretória/genética , Regiões Promotoras Genéticas , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/genética , Regulação Bacteriana da Expressão Gênica , Lipoproteínas , Proteínas de MembranaRESUMO
The exceptional semiconducting properties of two-dimensional (2D) transition metal dichalcogenides (TMDs) have made them highly promising for the development of future electronic and optoelectronic devices. Extensive studies of TMDs are partly associated with their ability to generate 2D-confined hot carriers above the conduction band edges, enabling potential applications that rely on such transient excited states. In this work, room-temperature spatiotemporal hot carrier dynamics in monolayer MoS2 is studied by transient absorption microscopy (TAM), featuring an initial ultrafast expansion followed by a rapid negative diffusion, and ultimately a slow long-term expansion of the band edge C-excitons. We provide direct experimental evidence to identify the abnormal negative diffusion process as a spatial contraction of the hot carriers resulting from spatial variation in the hot phonon bottleneck effect due to the Gaussian intensity distribution of the pump laser beam.
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The partial information decomposition (PID) aims to quantify the amount of redundant information that a set of sources provides about a target. Here, we show that this goal can be formulated as a type of information bottleneck (IB) problem, termed the "redundancy bottleneck" (RB). The RB formalizes a tradeoff between prediction and compression: it extracts information from the sources that best predict the target, without revealing which source provided the information. It can be understood as a generalization of "Blackwell redundancy", which we previously proposed as a principled measure of PID redundancy. The "RB curve" quantifies the prediction-compression tradeoff at multiple scales. This curve can also be quantified for individual sources, allowing subsets of redundant sources to be identified without combinatorial optimization. We provide an efficient iterative algorithm for computing the RB curve.
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A central challenge in hypothesis testing (HT) lies in determining the optimal balance between Type I (false positive) and Type II (non-detection or false negative) error probabilities. Analyzing these errors' exponential rate of convergence, known as error exponents, provides crucial insights into system performance. Error exponents offer a lens through which we can understand how operational restrictions, such as resource constraints and impairments in communications, affect the accuracy of distributed inference in networked systems. This survey presents a comprehensive review of key results in HT, from the foundational Stein's Lemma to recent advancements in distributed HT, all unified through the framework of error exponents. We explore asymptotic and non-asymptotic results, highlighting their implications for designing robust and efficient networked systems, such as event detection through lossy wireless sensor monitoring networks, collective perception-based object detection in vehicular environments, and clock synchronization in distributed environments, among others. We show that understanding the role of error exponents provides a valuable tool for optimizing decision-making and improving the reliability of networked systems.
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The transmission bottleneck, defined as the number of viruses that transmit from one host to infect another, is an important determinant of the rate of virus evolution and the level of immunity required to protect against virus transmission. Despite its importance, SARS-CoV-2's transmission bottleneck remains poorly characterized, in part due to a lack of quantitative measurement tools. To address this, we adapted a SARS-CoV-2 reverse genetics system to generate a pool of >200 isogenic SARS-CoV-2 viruses harboring specific 6-nucleotide barcodes inserted in ORF10, a non-translated ORF. We directly inoculated donor Syrian hamsters intranasally with this barcoded virus pool and exposed a paired naïve contact hamster to each donor. Following exposure, the nasal turbinates, trachea, and lungs were collected, viral titers were measured, and the number of barcodes in each tissue were enumerated to quantify the transmission bottleneck. The duration and route (airborne, direct contact, and fomite) of exposure were varied to assess their impact on the transmission bottleneck. In airborne-exposed hamsters, the transmission bottleneck increased with longer exposure durations. We found that direct contact exposure produced the largest transmission bottleneck (average 27 BCs), followed by airborne exposure (average 16 BCs) then fomite exposure (average 8 BCs). Interestingly, we detected unique BCs in both the upper and lower respiratory tract of contact animals from all routes of exposure, suggesting that SARS-CoV-2 can directly infect hamster lungs. Altogether, these findings highlight the utility of barcoded viruses as tools to rigorously study virus transmission. In the future, barcoded SARS-CoV-2 will strengthen studies of immune factors that influence virus transmission.
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Two important characteristics of metapopulations are extinction-(re)colonization dynamics and gene flow between subpopulations. These processes can cause strong shifts in genome-wide allele frequencies that are generally not observed in "classical" (large, stable, and panmictic) populations. Subpopulations founded by one or a few individuals, the so-called propagule model, are initially expected to show intermediate allele frequencies at polymorphic sites until natural selection and genetic drift drive allele frequencies toward a mutation-selection-drift equilibrium characterized by a negative exponential-like distribution of the site frequency spectrum. We followed changes in site frequency spectrum distribution in a natural metapopulation of the cyclically parthenogenetic pond-dwelling microcrustacean Daphnia magna using biannual pool-seq samples collected over a 5-yr period from 118 ponds occupied by subpopulations of known age. As expected under the propagule model, site frequency spectra in newly founded subpopulations trended toward intermediate allele frequencies and shifted toward right-skewed distributions as the populations aged. Immigration and subsequent hybrid vigor altered this dynamic. We show that the analysis of site frequency spectrum dynamics is a powerful approach to understand evolution in metapopulations. It allowed us to disentangle evolutionary processes occurring in a natural metapopulation, where many subpopulations evolve in parallel. Thereby, stochastic processes like founder and immigration events lead to a pattern of subpopulation divergence, while genetic drift leads to converging site frequency spectrum distributions in the persisting subpopulations. The observed processes are well explained by the propagule model and highlight that metapopulations evolve differently from classical populations.
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Daphnia , Frequência do Gene , Deriva Genética , Seleção Genética , Animais , Daphnia/genética , Fluxo Gênico , Modelos Genéticos , Genética Populacional/métodos , Dinâmica Populacional , Genoma , Evolução Biológica , Evolução MolecularRESUMO
This study is the first report to characterize the Rhodus uyekii genome and study the development of microsatellite markers and their markers applied to the genetic structure of the wild population. Genome assembly was based on PacBio HiFi and Illumina HiSeq paired-end sequencing, resulting in a draft genome assembly of R. uyekii. The draft genome was assembled into 2652 contigs. The integrity assessment of the assemblies indicates that the quality of the draft assemblies is high, with 3259 complete BUSCOs (97.2%) in the database of Verbrata. A total of 31,166 predicted protein-coding genes were annotated in the protein database. The phylogenetic tree showed that R. uyekii is a close but distinct relative of Onychostoma macrolepis. Among the 10 fish genomes, there were significant gene family expansions (8-2387) and contractions (16-2886). The average number of alleles amplified by the 21 polymorphic markers ranged from 6 to 23, and the average PIC value was 0.753, which will be useful for evolutionary and genetic analysis. Using population genetic analysis, we analyzed genetic diversity and the genetic structures of 120 individuals from 6 populations. The average number of alleles per population ranged from 7.6 to 9.9, observed heterozygosity ranged from 0.496 to 0.642, and expected heterozygosity ranged from 0.587 to 0.783. Discriminant analysis of principal components According to the analysis method, the population was divided into three populations (BS vs. DC vs. GG, GC, MS, DC). In conclusion, our study provides a useful resource for comparative genomics, phylogeny, and future population studies of R. uyekii.
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Variação Genética , Repetições de Microssatélites , Filogenia , Repetições de Microssatélites/genética , República da Coreia , Animais , Genética Populacional , Cyprinidae/genética , Cyprinidae/classificação , Genoma , Sequenciamento Completo do Genoma/métodosRESUMO
In digital baseband processing, the forward error correction (FEC) unit belongs to the most demanding components in terms of computational complexity and power consumption. Hence, efficient implementation of FEC decoders is crucial for next-generation mobile broadband standards and an ongoing research topic. Quantization has a significant impact on the decoder area, power consumption and throughput. Thus, lower bit widths are preferred for efficient implementations but degrade the error correction capability. To address this issue, a non-uniform quantization based on the Information Bottleneck (IB) method is proposed that enables a low bit width while maintaining the essential information. Many investigations on the use of the IB method for Low-density parity-check code) LDPC decoders exist and have shown its advantages from an implementation perspective. However, for polar code decoder implementations, there exists only one publication that is not based on the state-of-the-art Fast Simplified Successive-Cancellation (Fast-SSC) decoding algorithm, and only synthesis implementation results without energy estimation are shown. In contrast, our paper presents several optimized Fast-SSC polar code decoder implementations using IB-based quantization with placement and routing results using advanced 12 nm FinFET technology. Gains of up to 16% in area and 13% in energy efficiency are achieved with IB-based quantization at a Frame Error Rate (FER) of 10-7 and a polar code of N=1024,R=0.5 compared to state-of-the-art decoders.
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A number of species have recently recovered from near-extinction. Although these species have avoided the immediate extinction threat, their long-term viability remains precarious due to the potential genetic consequences of population declines, which are poorly understood on a timescale beyond a few generations. Woolly mammoths (Mammuthus primigenius) became isolated on Wrangel Island around 10,000 years ago and persisted for over 200 generations before becoming extinct around 4,000 years ago. To study the evolutionary processes leading up to the mammoths' extinction, we analyzed 21 Siberian woolly mammoth genomes. Our results show that the population recovered quickly from a severe bottleneck and remained demographically stable during the ensuing six millennia. We find that mildly deleterious mutations gradually accumulated, whereas highly deleterious mutations were purged, suggesting ongoing inbreeding depression that lasted for hundreds of generations. The time-lag between demographic and genetic recovery has wide-ranging implications for conservation management of recently bottlenecked populations.