Search

A combination of evidence, based on genetic, fossil and archaeological findings, indicates that Homo sapiens spread out of Africa between ~70-60 thousand years ago (kya). However, it appears that once outside of Africa, human populations did not expand across all of Eurasia until ~45 kya. The geographic whereabouts of these early settlers in the timeframe between ~70-60 to 45 kya has been difficult to reconcile. Here we combine genetic evidence and palaeoecological models to infer the geographic location that acted as the Hub for our species during the early phases of colonisation of Eurasia. Leveraging on available genomic evidence we show that populations from the Persian Plateau carry an ancestry component that closely matches the population that settled the Hub outside Africa. With the paleoclimatic data available to date, we built ecological models showing that the Persian Plateau was suitable for human occupation and that it could sustain a larger population compared to other West Asian regions, strengthening this claim. [ABSTRACT FROM AUTHOR]

Following the development of modern genome sequencing technologies, the investigation of museum osteological finds is increasingly informative and popular. Viable protocols to help preserve these collections from exceedingly invasive analyses, would allow greater access to the specimens for scientific research. The main aim of this work is to survey skeletal tissues, specifically petrous bones and roots of teeth, using infrared spectroscopy as a prescreening method to assess the bone quality for molecular analyses. This approach could overcome the major problem of identifying useful genetic material in archaeological bone collections without resorting to demanding, time consuming and expensive laboratory studies. A minimally invasive sampling of archaeological bones was developed and bone structural and compositional changes were examined, linking isotopic and genetic data to infrared spectra. The predictive model based on Infrared parameters is effective in determining the occurrence of ancient DNA (aDNA); however, the quality/quantity of aDNA cannot be determined because of the influence of environmental and local factors experienced by the examined bones during the burial period. [ABSTRACT FROM AUTHOR]

For an increasing number of applications, the quality and the stability of manufacturing processes can be determined via image and video-image data analysis and new techniques are required to extract and synthesize the relevant information content enclosed in big sensor data to draw conclusions about the process and the final part quality. This paper focuses on video image data where the phenomena under study is captured by a point process whose spatial signature is of interest. A novel approach is proposed which combines spatial data modeling via Ripley's K-function with Functional Analysis of Variance (FANOVA), i.e., Analysis of Variance on Functional data. The K-function allows to synthesize the spatial pattern information in a function while preserving the capability to capture changes in the process behavior. The method is applicable to quantities and phenomena that can be represented as clusters, or clouds, of spatial points evolving over time. In our case, the motivating case study regards the analysis of spatter ejections caused by the laser-material interaction in Additive Manufacturing via Laser Powder Bed Fusion (L-PBF). The spatial spread of spatters, captured in the form of point particles through in-situ high speed machine vision, can be used as a proxy to select the best conditions to avoid defects (pores) in the manufactured part. The proposed approach is shown to be not only an efficient way to translate the high-dimensional video image data into a lower dimensional format (the K-function curves), but also more effective than benchmark methods in detecting departures from a stable and in-control state. [ABSTRACT FROM AUTHOR]

The wild boar (Sus scrofa meridionalis) arrived in Sardinia with the first human settlers in the early Neolithic with the potential to hybridize with the domestic pig (S. s. domesticus) throughout its evolution on the island. In this paper, we investigated the possible microevolutionary effects of such introgressive hybridization on the present wild boar population, comparing Sardinian wild specimens with several commercial pig breeds and Sardinian local pigs, along with a putatively unadmixed wild boar population from Central Italy, all genotyped with a medium density SNP chip. We first aimed at identifying hybrids in the population using different approaches, then examined genomic regions enriched for domestic alleles in the hybrid group, and finally we applied two methods to find regions under positive selection to possibly highlight instances of domestic adaptive introgression into a wild population. We found three hybrids within the Sardinian sample (3.1% out of the whole dataset). We reported 11 significant windows under positive selection with a method that looks for overly differentiated loci in the target population, compared with other two populations. We also identified 82 genomic regions with signs of selection in the domestic pig but not in the wild boar, two of which overlapped with genomic regions enriched for domestic alleles in the hybrid pool. Genes in these regions can be linked with reproductive success. Given our results, domestic introgression does not seem to be pervasive in the Sardinian wild boar. Nevertheless, we suggest monitoring the possible spread of advantageous domestic alleles in the coming years. [ABSTRACT FROM AUTHOR]

The Italian Peninsula, a natural pier across the Mediterranean Sea, witnessed intricate population events since the very beginning of the human occupation in Europe. In the last few years, an increasing number of modern and ancient genomes from the area have been published by the international research community. This genomic perspective started unveiling the relevance of Italy to understand the post-Last Glacial Maximum (LGM) re-peopling of Europe, the earlier phase of the Neolithic westward migrations, and its linking role between Eastern and Western Mediterranean areas after the Iron Age. However, many open questions are still waiting for more data to be addressed in full. With this review, we summarize the current knowledge emerging from the available ancient Italian individuals and, by re-analysing them all at once, we try to shed light on the avenues future research in the area should cover. In particular, open questions concern (1) the fate of pre-Villabruna Europeans and to what extent their genomic components were absorbed by the post-LGM hunter-gatherers; (2) the role of Sicily and Sardinia before LGM; (3) to what degree the documented genetic structure within the Early Neolithic settlers can be described as two separate migrations; (4) what are the population events behind the marked presence of an Iranian Neolithic-like component in Bronze Age and Iron Age Italian and Southern European samples. [ABSTRACT FROM AUTHOR]

We consider the treatment of fermionic dark matter interacting with photons via dimension-5 and -6 effective operators, arguing that one should always use hypercharge gauge field form factors, instead of those of the photon. Beyond the simple observation that the electromagnetic form factor description breaks down at the electroweak scale, we show how the additional couplings to the Z boson predicted by the hypercharge form factors modify the relic density calculation and indirect detection limits for dark matter masses of a few tens of GeV and above. Furthermore, constraints from the invisible Z decay width can be competitive for masses below 10 GeV. We review the phenomenology of hypercharge form factors at the LHC as well as for direct and indirect detection experiments. We highlight where the electromagnetic and hypercharge descriptions lead to wildly different conclusions about the viable parameter space and the relative sensitivity of various probes, namely vector boson fusion versus mono-jet constraints from the LHC, and indirect versus direct searches, for larger dark matter masses. We find that the dimension-5 operators are strongly constrained by direct detection bounds, while for dimension-6 operators LHC mono-jet searches are competitive or better than the other probes we consider. [ABSTRACT FROM AUTHOR]

In this paper, a characterisation of diamond abrasive grains of grinding tools using industrial X-ray computed tomography (XCT) is carried out. One of the most challenge tasks in the characterisation is extracting the diamond abrasive grains from the XCT volume data. Methods that are able to extract the grains are then developed and introduced in this paper. The first step is to create a triangular mesh surface from the reconstructed volume file using a gradient anisotropic diffusion filter. The second step is to convert the measured greyscale volume into a signed distance field using a global threshold value and then a localised method for grain segmentation. To validate the proposed method, three different types of grinding tool specimens are measured and analysed. Each abrasive grain is segmented and the distributions of grains (with both random and designed patterns) are then calculated, plotted and analysed. The quantitative analysis clearly shows the deviations between the measured distribution and the designed pattern of the grinding tool, which indicates that the proposed method can provide an accurate and comprehensive characterisation of the grinding tools. [ABSTRACT FROM AUTHOR]

In the growing Industry 4.0 market, there is strong need to implement automatic inspection methods to support manufacturing processes. Tool wear in turning is one of the biggest concerns that most expert operators are able to indirectly infer through the analysis of the removed chips. Automatising this operation would enable developing more efficient cutting processes that turns in easier process planning management toward the Zero Defect Manufacturing paradigm. This paper presents a deep learning approach, based on image processing applied to turning chips for indirectly identifying tool wear levels. The procedure extracts different indicators from the RGB and HSV image channels and instructs a neural network for classifying the chips, based on tool state conditions. Images were collected with a high-resolution digital camera during an experimental cutting campaign involving tool wear analysis with direct microscope imaging. The sensitivity analysis confirmed that the most sensible image channels are the hue value H that were used to teach the network, leading to performances in the range of 95 of proper classification. The feasibility of the deep learning approach for indirectly understanding the tool wear from the chip colour characterisation is confirmed. However, due to the big effects on chip colours of variables as the workpiece material and cutting process parameters, the applicability is limited to stable production flows. An industrial implementation can be foreseen by populating proper large databases and by implementing real-time chip segmentation analysis. [ABSTRACT FROM AUTHOR]

Polygenic Scores (PSs) describe the genetic component of an individual's quantitative phenotype or their susceptibility to diseases with a genetic basis. Currently, PSs rely on population-dependent contributions of many associated alleles, with limited applicability to understudied populations and recently admixed individuals. Here we introduce a combination of local ancestry deconvolution and partial PS computation to account for the population-specific nature of the association signals in individuals with admixed ancestry. We demonstrate partial PS to be a proxy for the total PS and that a portion of the genome is enough to improve susceptibility predictions for the traits we test. By combining partial PSs from different populations, we are able to improve trait predictability in admixed individuals with some European ancestry. These results may extend the applicability of PSs to subjects with a complex history of admixture, where current methods cannot be applied. Polygenic scores are believed to hold future promise for trait prediction and personalized medicine, but are sensitive to demographic history. Here, Marnetto et al. develop partial polygenic scores supplemented with local ancestry deconvolution which improves prediction accuracy into recently admixed European populations. [ABSTRACT FROM AUTHOR]

The presence of genomic signatures of Eurasian origin in contemporary Ethiopians has been reported by several authors and estimated to have arrived in the area from 3000 years ago. Several studies reported plausible source populations for such a signature, using haplotype based methods on modern data or single-site methods on modern or ancient data. These studies did not reach a consensus and suggested an Anatolian or Sardinia-like proxy, broadly Levantine or Neolithic Levantine as possible sources. We demonstrate, however, that the deeply divergent, autochthonous African component which accounts for ~50% of most contemporary Ethiopian genomes, affects the overall allele frequency spectrum to an extent that makes it hard to control for it and, at once, to discern between subtly different, yet important, Eurasian sources (such as Anatolian or Levant Neolithic ones). Here we re-assess pattern of allele sharing between the Eurasian component of Ethiopians (here called "NAF" for Non African) and ancient and modern proxies. Our results unveil a genomic legacy that may connect the Eurasian genetic component of contemporary Ethiopians with Sea People and with population movements that affected the Mediterranean area and the Levant after the fall of the Minoan civilization. [ABSTRACT FROM AUTHOR]

High-coverage whole-genome sequence studies have so far focused on a limited number of geographically restricted populations, or been targeted at specific diseases, such as cancer. Nevertheless, the availability of high-resolution genomic data has led to the development of new methodologies for inferring population history and refuelled the debate on the mutation rate in humans. Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets. We analyse this dataset to refine estimates of continent-wide patterns of heterozygosity, long- and short-distance gene flow, archaic admixture, and changes in effective population size through time as well as for signals of positive or balancing selection. We find a genetic signature in present-day Papuans that suggests that at least 2% of their genome originates from an early and largely extinct expansion of anatomically modern humans (AMHs) out of Africa. Together with evidence from the western Asian fossil record, and admixture between AMHs and Neanderthals predating the main Eurasian expansion, our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75,000 years ago. [ABSTRACT FROM AUTHOR]

In this paper a fusion metamodeling approach is suggested as a method for reducing the experimental and computational effort generally required for calibrating the parameters of FEM simulations models. The metamodel is used inside an optimization routine for linking data coming from two different sources: simulations and experiments. The method is applied to a real problem: the optimal design of a metal foam filled tube to be used as an anti-intrusion bar in vehicles. The model is hierarchical, in the sense that one set of data (the experiments) is considered to be more reliable and it is labeled as 'high-fidelity' and the other set (the simulations) is labeled as 'low-fidelity'. In the proposed approach, Gaussian models are used to describe results of computer experiments because they are flexible and they can easily interpolate data coming from deterministic simulations. Since the results of experiments are obviously fully accurate, but aleatory, a second stage ('linkage') model is used, which adjusts the prediction provided by the first model to more accurately represent the real experimental data. In the paper, the modeling and prediction ability of the method is first demonstrated and explained by means of artificially generated data and then applied to the optimization of foam filled tubular structures. The fusion metamodel yields comparable predictions (and optimal solution) if built over calibrated simulations vs. non-calibrated FEM models. [ABSTRACT FROM AUTHOR]

Given the importance of Africa to studies of human origins and disease susceptibility, detailed characterization of African genetic diversity is needed. The African Genome Variation Project provides a resource with which to design, implement and interpret genomic studies in sub-Saharan Africa and worldwide. The African Genome Variation Project represents dense genotypes from 1,481 individuals and whole-genome sequences from 320 individuals across sub-Saharan Africa. Using this resource, we find novel evidence of complex, regionally distinct hunter-gatherer and Eurasian admixture across sub-Saharan Africa. We identify new loci under selection, including loci related to malaria susceptibility and hypertension. We show that modern imputation panels (sets of reference genotypes from which unobserved or missing genotypes in study sets can be inferred) can identify association signals at highly differentiated loci across populations in sub-Saharan Africa. Using whole-genome sequencing, we demonstrate further improvements in imputation accuracy, strengthening the case for large-scale sequencing efforts of diverse African haplotypes. Finally, we present an efficient genotype array design capturing common genetic variation in Africa. [ABSTRACT FROM AUTHOR]

We have surveyed 15 high-altitude adaptation candidate genes for signals of positive selection in North Caucasian highlanders using targeted re-sequencing. A total of 49 unrelated Daghestani from three ethnic groups (Avars, Kubachians, and Laks) living in ancient villages located at around 2,000 m above sea level were chosen as the study population. Caucasian (Adygei living at sea level, N = 20) and CEU (CEPH Utah residents with ancestry from northern and western Europe; N = 20) were used as controls. Candidate genes were compared with 20 putatively neutral control regions resequenced in the same individuals. The regions of interest were amplified by long-PCR, pooled according to individual, indexed by adding an eight-nucleotide tag, and sequenced using the Illumina GAII platform. 1,066 SNPs were called using false discovery and false negative thresholds of ~6%. The neutral regions provided an empirical null distribution to compare with the candidate genes for signals of selection. Two genes stood out. In Laks, a non-synonymous variant within HIF1A already known to be associated with improvement in oxygen metabolism was rediscovered, and in Kubachians a cluster of 13 SNPs located in a conserved intronic region within EGLN1 showing high population differentiation was found. These variants illustrate both the common pathways of adaptation to high altitude in different populations and features specific to the Daghestani populations, showing how even a mildly hypoxic environment can lead to genetic adaptation. [ABSTRACT FROM AUTHOR]

The Caucasus region is a complex cultural and ethnic mosaic, comprising populations that speak Caucasian, Indo-European and Altaic languages. Isolated mountain villages (auls) in Dagestan still preserve high level of genetic and cultural diversity and have patriarchal societies with a long history of isolation. The aim of this study was to understand the genetic history of five Dagestan highland auls with distinct ethnic affiliation (Avars, Chechens-Akkins, Kubachians, Laks, Tabasarans) using markers on the male-specific region of the Y chromosome. The groups analyzed here are all Muslims but speak different languages all belonging to the Nakh-Dagestanian linguistic family. The results show that the Dagestan ethnic groups share a common Y-genetic background, with deep-rooted genealogies and rare alleles, dating back to an early phase in the post-glacial recolonization of Europe. Geography and stochastic factors, such as founder effect and long-term genetic drift, driven by the rigid structuring of societies in groups of patrilineal descent, most likely acted as mutually reinforcing key factors in determining the high degree of Y-genetic divergence among these ethnic groups. [ABSTRACT FROM AUTHOR]

The survival of indigenous European wildcat (Felis silvestris silvestris) populations can be locally threatened by introgressive hybridization with free-ranging domestic cats. Identifying pure wildcats and investigating the ancestry of admixed individuals becomes thus a conservation priority. We analyzed 63k cat Single Nucleotide Polymorphisms (SNPs) with multivariate, Bayesian and gene-search tools to better evaluate admixture levels between domestic and wild cats collected in Europe, timing and ancestry proportions of their hybrids and backcrosses, and track the origin (wild or domestic) of the genomic blocks carried by admixed cats, also looking for possible deviations from neutrality in their inheritance patterns. Small domestic ancestry blocks were detected in the genomes of most admixed cats, which likely originated from hybridization events occurring from 6 to 22 generations in the past. We identified about 1,900 outlier coding genes with excess of wild or domestic ancestry compared to random expectations in the admixed individuals. More than 600 outlier genes were significantly enriched for Gene Ontology (GO) categories mainly related to social behavior, functional and metabolic adaptive processes (wild-like genes), involved in cognition and neural crest development (domestic-like genes), or associated with immune system functions and lipid metabolism (parental-like genes). These kinds of genomic ancestry analyses could be reliably applied to unravel the admixture dynamics in European wildcats, as well as in other hybridizing populations, in order to design more efficient conservation plans. [ABSTRACT FROM AUTHOR]

Ancient DNA is revealing new insights into the genetic relationship between Pleistocene hominins and modern humans. Nuclear DNA indicated Neanderthals as a sister group of Denisovans after diverging from modern humans. However, the closer affinity of the Neanderthal mitochondrial DNA (mtDNA) to modern humans than Denisovans has recently been suggested as the result of gene flow from an African source into Neanderthals before 100,000 years ago. Here we report the complete mtDNA of an archaic femur from the Hohlenstein-Stadel (HST) cave in southwestern Germany. HST carries the deepest divergent mtDNA lineage that splits from other Neanderthals ∼270,000 years ago, providing a lower boundary for the time of the putative mtDNA introgression event. We demonstrate that a complete Neanderthal mtDNA replacement is feasible over this time interval even with minimal hominin introgression. The highly divergent HST branch is indicative of greater mtDNA diversity during the Middle Pleistocene than in later periods. [ABSTRACT FROM AUTHOR]

Human populations are often dichotomized into 'isolated' and 'open' categories using cultural and/or geographical barriers to gene flow as differential criteria. Although widespread, the use of these alternative categories could obscure further heterogeneity due to inter-population differences in effective size, growth rate, and timing or amount of gene flow. We compared intra and inter-population variation measures combining novel and literature data relative to 87,818 autosomal SNPs in 14 open populations and 10 geographic and/or linguistic European isolates. Patterns of intra-population diversity were found to vary considerably more among isolates, probably due to differential levels of drift and inbreeding. The relatively large effective size estimated for some population isolates challenges the generalized view that they originate from small founding groups. Principal component scores based on measures of intra-population variation of isolated and open populations were found to be distributed along a continuum, with an area of intersection between the two groups. Patterns of inter-population diversity were even closer, as we were able to detect some differences between population groups only for a few multidimensional scaling dimensions. Therefore, different lines of evidence suggest that dichotomizing human populations into open and isolated groups fails to capture the actual relations among their genomic features. [ABSTRACT FROM AUTHOR]

Humans have more copies of amylase genes than other primates. It is still poorly understood, however, when the copy number expansion occurred and whether its spread was enhanced by selection. Here we assess amylase copy numbers in a global sample of 480 high coverage genomes and find that regions flanking the amylase locus show notable depression of genetic diversity both in African and non-African populations. Analysis of genetic variation in these regions supports the model of an early selective sweep in the human lineage after the split of humans from Neanderthals which led to the fixation of multiple copies of AMY1 in place of a single copy. We find evidence of multiple secondary losses of copy number with the highest frequency (52%) of a deletion of AMY2A and associated low copy number of AMY1 in Northeast Siberian populations whose diet has been low in starch content. [ABSTRACT FROM AUTHOR]

A number of studies have demonstrated that bone scintigraphy has high sensitivity and efficacy in the early detection of bone metastases from several tumours, including breast cancer. Bone scintigraphy is the most definitive tool for diagnosing and monitoring metastatic spread of breast cancer. However, in the past decade there has been a wide debate on its impact on survival time, morbidity and quality of life. Worldwide economic restrictions and these studies have led to the adoption of an almost minimalist policy for breast cancer follow-up using evidence-based guidelines. The recommended breast cancer surveillance testing includes only a few procedures (history, physical and breast self-examination, patient education on symptoms, pelvic examination). The routine use of additional tests, such as blood cell count, tumour markers, liver ultrasonography, bone scan and chest X-rays, is not recommended. Accordingly, scintigraphy should be reserved for a limited number of patients. On the other hand, early diagnosis of bone involvement may reduce the risk of skeletal related events, thus leading to a significant improvement in quality of life. Furthermore, new drugs (e.g. bisphosphonates) can now delay the onset of bone metastasis and reduce the number of patients who experience skeletal complications. In conclusion, the evidence of the clinical usefulness of bone scintigraphy (to allow early planning of new treatments in advanced disease) has to be re-evaluated, possibly by large randomised prospective trials. [ABSTRACT FROM AUTHOR]