University of Puerto Rico-Mayaguez

The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies. Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics. The 1000 Genomes Project has sought to comprehensively catalogue human genetic variation across populations, providing a valuable public genomic resource. The data obtained so far have found applications ranging from association studies and fine mapping studies to the filtering of likely neutral variants in rare-disease cohorts. The authors now report on the final phase of the project, phase 3, which covers previously uncharacterized areas of human genetic diversity in terms of the populations sampled and categories of characterized variation. The sample now includes more than 2,500 individuals from 26 global populations, with low coverage whole-genome and deep exome sequencing, as well as dense microarray genotyping. They find that while most common variants are shared across populations, rarer variants are often restricted to closely related populations. The authors also demonstrate the use of the phase 3 dataset as a reference panel for imputation to improve the resolution in genetic association studies.

By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination of low-coverage whole-genome and exome sequencing. By developing methods to integrate information across several algorithms and diverse data sources, we provide a validated haplotype map of 38 million single nucleotide polymorphisms, 1.4 million short insertions and deletions, and more than 14,000 larger deletions. We show that individuals from different populations carry different profiles of rare and common variants, and that low-frequency variants show substantial geographic differentiation, which is further increased by the action of purifying selection. We show that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites. This resource, which captures up to 98% of accessible single nucleotide polymorphisms at a frequency of 1% in related populations, enables analysis of common and low-frequency variants in individuals from diverse, including admixed, populations. This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual. This report by the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations. Integrative analyses reveal profiles of rare and common variants in different populations. The frequencies of rare variants vary across biological pathways, and hundreds of rare, non-coding variants at conserved sites — such as changes disrupting transcription-factor motifs — can be established for each individual.

African Americans have higher rates of kidney disease than European Americans. Here, we show that, in African Americans, focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (H-ESKD) are associated with two independent sequence variants in the APOL1 gene on chromosome 22 {FSGS odds ratio = 10.5 [95% confidence interval (CI) 6.0 to 18.4]; H-ESKD odds ratio = 7.3 (95% CI 5.6 to 9.5)}. The two APOL1 variants are common in African chromosomes but absent from European chromosomes, and both reside within haplotypes that harbor signatures of positive selection. ApoL1 (apolipoprotein L-1) is a serum factor that lyses trypanosomes. In vitro assays revealed that only the kidney disease-associated ApoL1 variants lysed Trypanosoma brucei rhodesiense. We speculate that evolution of a critical survival factor in Africa may have contributed to the high rates of renal disease in African Americans.

Assessing Biodiversity Declines Understanding human impact on biodiversity depends on sound quantitative projection. Pereira et al. (p. 1496 , published online 26 October) review quantitative scenarios that have been developed for four main areas of concern: species extinctions, species abundances and community structure, habitat loss and degradation, and shifts in the distribution of species and biomes. Declines in biodiversity are projected for the whole of the 21st century in all scenarios, but with a wide range of variation. Hoffmann et al. (p. 1503 , published online 26 October) draw on the results of five decades' worth of data collection, managed by the International Union for Conservation of Nature Species Survival Commission. A comprehensive synthesis of the conservation status of the world's vertebrates, based on an analysis of 25,780 species (approximately half of total vertebrate diversity), is presented: Approximately 20% of all vertebrate species are at risk of extinction in the wild, and 11% of threatened birds and 17% of threatened mammals have moved closer to extinction over time. Despite these trends, overall declines would have been significantly worse in the absence of conservation actions.

Abstract We report multiple lines of evidence for a stochastic signal that is correlated among 67 pulsars from the 15 yr pulsar timing data set collected by the North American Nanohertz Observatory for Gravitational Waves. The correlations follow the Hellings–Downs pattern expected for a stochastic gravitational-wave background. The presence of such a gravitational-wave background with a power-law spectrum is favored over a model with only independent pulsar noises with a Bayes factor in excess of 10 14 , and this same model is favored over an uncorrelated common power-law spectrum model with Bayes factors of 200–1000, depending on spectral modeling choices. We have built a statistical background distribution for the latter Bayes factors using a method that removes interpulsar correlations from our data set, finding p = 10 −3 (≈3 σ ) for the observed Bayes factors in the null no-correlation scenario. A frequentist test statistic built directly as a weighted sum of interpulsar correlations yields p = 5 × 10 −5 to 1.9 × 10 −4 (≈3.5 σ –4 σ ). Assuming a fiducial f −2/3 characteristic strain spectrum, as appropriate for an ensemble of binary supermassive black hole inspirals, the strain amplitude is <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:msubsup> <mml:mrow> <mml:mn>2.4</mml:mn> </mml:mrow> <mml:mrow> <mml:mo>−</mml:mo> <mml:mn>0.6</mml:mn> </mml:mrow> <mml:mrow> <mml:mo>+</mml:mo> <mml:mn>0.7</mml:mn> </mml:mrow> </mml:msubsup> <mml:mo>×</mml:mo> <mml:msup> <mml:mrow> <mml:mn>10</mml:mn> </mml:mrow> <mml:mrow> <mml:mo>−</mml:mo> <mml:mn>15</mml:mn> </mml:mrow> </mml:msup> </mml:math> (median + 90% credible interval) at a reference frequency of 1 yr −1 . The inferred gravitational-wave background amplitude and spectrum are consistent with astrophysical expectations for a signal from a population of supermassive black hole binaries, although more exotic cosmological and astrophysical sources cannot be excluded. The observation of Hellings–Downs correlations points to the gravitational-wave origin of this signal.

Microbial ecology is plagued by problems of an abstract nature. Cell sizes are so small and population sizes so large that both are virtually incomprehensible. Niches are so far from our everyday experience as to make their very definition elusive. Organisms that may be abundant and critical to our survival are little understood, seldom described and/or cultured, and sometimes yet to be even seen. One way to confront these problems is to use data of an even more abstract nature: molecular sequence data. Massive environmental nucleic acid sequencing, such as metagenomics or metatranscriptomics, promises functional analysis of microbial communities as a whole, without prior knowledge of which organisms are in the environment or exactly how they are interacting. But sequence-based ecological studies nearly always use a comparative approach, and that requires relevant reference sequences, which are an extremely limited resource when it comes to microbial eukaryotes [1]. In practice, this means sequence databases need to be populated with enormous quantities of data for which we have some certainties about the source. Most important is the taxonomic identity of the organism from which a sequence is derived and as much functional identification of the encoded proteins as possible. In an ideal world, such information would be available as a large set of complete, well-curated, and annotated genomes for all the major organisms from the environment in question. Reality substantially diverges from this ideal, but at least for bacterial molecular ecology, there is a database consisting of thousands of complete genomes from a wide range of taxa, supplemented by a phylogeny-driven approach to diversifying genomics [2]. For eukaryotes, the number of available genomes is far, far fewer, and we have relied much more heavily on random growth of sequence databases [3],[4], raising the question as to whether this is fit for purpose.

This article reports or, the international Nanofluid Property Benchmark Exercise, or INPBE. in which the thermal conductivity of identical samples of colloidally stable dispersions of nanoparticles or &amp;quot;nanofluids&amp;quot;, was measured by over 30 organizations worldwide, using, a variety of experimental approaches, including the transient hot wire method, steady-state methods, and optical methods. The nanofluids tested in the exercise were comprised of aqueous and nonaqueous basefluids, metal and metal oxide particles, near-spherical and elongated particles, at low and high particle concentrations. The data analysis reveals that the data from most organizations lie within a relatively narrow band (+/- 10% or less) about the sample average with only few outliers. The thermal conductivity of the nanofluids was found to increase with particle concentration and aspect ratio. as expected from classical theory. There are (small) systematic differences in the absolute values of the nanofluid thermal conductivity among the various experimental approaches; however. such differences tend to disappear when the data are normalized to the Measured thermal conductivity of the basefluid. The effective medium theory developed for dispersed particles by Maxwell in 1881 and recently generalized by Nan et al. [J. Appl. Phys. 81, 6692 (1997)], was found to be in good agreement with the experimental data, suggesting that no anomalous enhancement of thermal conductivity was achieved in the nanofluids tested in this exercise.

The use of bone grafts is the standard to treat skeletal fractures, or to replace and regenerate lost bone, as demonstrated by the large number of bone graft procedures performed worldwide. The most common of these is the autograft, however, its use can lead to complications such as pain, infection, scarring, blood loss, and donor-site morbidity. The alternative is allografts, but they lack the osteoactive capacity of autografts and carry the risk of carrying infectious agents or immune rejection. Other approaches, such as the bone graft substitutes, have focused on improving the efficacy of bone grafts or other scaffolds by incorporating bone progenitor cells and growth factors to stimulate cells. An ideal bone graft or scaffold should be made of biomaterials that imitate the structure and properties of natural bone ECM, include osteoprogenitor cells and provide all the necessary environmental cues found in natural bone. However, creating living tissue constructs that are structurally, functionally and mechanically comparable to the natural bone has been a challenge so far. This focus of this review is on the evolution of these scaffolds as bone graft substitutes in the process of recreating the bone tissue microenvironment, including biochemical and biophysical cues.

BACKGROUND: The rising temperature of the world's oceans has become a major threat to coral reefs globally as the severity and frequency of mass coral bleaching and mortality events increase. In 2005, high ocean temperatures in the tropical Atlantic and Caribbean resulted in the most severe bleaching event ever recorded in the basin. METHODOLOGY/PRINCIPAL FINDINGS: Satellite-based tools provided warnings for coral reef managers and scientists, guiding both the timing and location of researchers' field observations as anomalously warm conditions developed and spread across the greater Caribbean region from June to October 2005. Field surveys of bleaching and mortality exceeded prior efforts in detail and extent, and provided a new standard for documenting the effects of bleaching and for testing nowcast and forecast products. Collaborators from 22 countries undertook the most comprehensive documentation of basin-scale bleaching to date and found that over 80% of corals bleached and over 40% died at many sites. The most severe bleaching coincided with waters nearest a western Atlantic warm pool that was centered off the northern end of the Lesser Antilles. CONCLUSIONS/SIGNIFICANCE: Thermal stress during the 2005 event exceeded any observed from the Caribbean in the prior 20 years, and regionally-averaged temperatures were the warmest in over 150 years. Comparison of satellite data against field surveys demonstrated a significant predictive relationship between accumulated heat stress (measured using NOAA Coral Reef Watch's Degree Heating Weeks) and bleaching intensity. This severe, widespread bleaching and mortality will undoubtedly have long-term consequences for reef ecosystems and suggests a troubled future for tropical marine ecosystems under a warming climate.

Results on two-particle angular correlations for charged particles emitted in proton-proton collisions at center-of-mass energies of 0.9, 2.36, and 7 TeV are presented, using data collected with the CMS detector over a broad range of pseudorapidity () and azimuthal angle (). Short-range correlations in , which are studied in minimum bias events, are characterized using a simple "independent cluster" parametrization in order to quantify their strength (cluster size) and their extent in (cluster decay width). Long-range azimuthal correlations are studied differentially as a function of charged particle multiplicity and particle transverse momentum using a 980 nb -1 data set at 7 TeV. In high multiplicity events, a pronounced structure emerges in the two-dimensional correlation function for particle pairs with intermediate p T of 1-3 GeV/c, 2.0 < || < 4.8 and 0. This is the first observation of such a long-range, near-side feature in two-particle correlation functions in pp or pp collisions.

Vehicles on the road with some common interests can cooperatively form a platoon-based driving pattern, in which a vehicle follows another vehicle and maintains a small and nearly constant distance to the preceding vehicle. It has been proved that, compared with driving individually, such a platoon-based driving pattern can significantly improve road capacity and energy efficiency. Moreover, with the emerging vehicular ad hoc network (VANET), the performance of a platoon in terms of road capacity, safety, energy efficiency, etc., can be further improved. On the other hand, the physical dynamics of vehicles inside the platoon can also affect the performance of a VANET. Such a complex system can be considered a platoon-based vehicular cyber-physical system (VCPS), which has attracted significant attention recently. In this paper, we present a comprehensive survey on a platoon-based VCPS. We first review the related work of a platoon-based VCPS. We then introduce two elementary techniques involved in a platoon-based VCPS, i.e., the vehicular networking architecture and standards, and traffic dynamics, respectively. We further discuss the fundamental issues in a platoon-based VCPS, including vehicle platooning/clustering, cooperative adaptive cruise control, platoon-based vehicular communications, etc., all of which are characterized by the tightly coupled relationship between traffic dynamics and VANET behaviors. Since system verification is critical to VCPS development, we also give an overview of VCPS simulation tools. Finally, we share our view on some open issues that may lead to new research directions.

Abstract The 15 yr pulsar timing data set collected by the North American Nanohertz Observatory for Gravitational Waves (NANOGrav) shows positive evidence for the presence of a low-frequency gravitational-wave (GW) background. In this paper, we investigate potential cosmological interpretations of this signal, specifically cosmic inflation, scalar-induced GWs, first-order phase transitions, cosmic strings, and domain walls. We find that, with the exception of stable cosmic strings of field theory origin, all these models can reproduce the observed signal. When compared to the standard interpretation in terms of inspiraling supermassive black hole binaries (SMBHBs), many cosmological models seem to provide a better fit resulting in Bayes factors in the range from 10 to 100. However, these results strongly depend on modeling assumptions about the cosmic SMBHB population and, at this stage, should not be regarded as evidence for new physics. Furthermore, we identify excluded parameter regions where the predicted GW signal from cosmological sources significantly exceeds the NANOGrav signal. These parameter constraints are independent of the origin of the NANOGrav signal and illustrate how pulsar timing data provide a new way to constrain the parameter space of these models. Finally, we search for deterministic signals produced by models of ultralight dark matter (ULDM) and dark matter substructures in the Milky Way. We find no evidence for either of these signals and thus report updated constraints on these models. In the case of ULDM, these constraints outperform torsion balance and atomic clock constraints for ULDM coupled to electrons, muons, or gluons.

Properties of the Higgs boson with mass near 125[Formula: see text] are measured in proton-proton collisions with the CMS experiment at the LHC. Comprehensive sets of production and decay measurements are combined. The decay channels include [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] pairs. The data samples were collected in 2011 and 2012 and correspond to integrated luminosities of up to 5.1[Formula: see text] at 7[Formula: see text] and up to 19.7[Formula: see text] at 8[Formula: see text]. From the high-resolution [Formula: see text] and [Formula: see text] channels, the mass of the Higgs boson is determined to be [Formula: see text]. For this mass value, the event yields obtained in the different analyses tagging specific decay channels and production mechanisms are consistent with those expected for the standard model Higgs boson. The combined best-fit signal relative to the standard model expectation is [Formula: see text] at the measured mass. The couplings of the Higgs boson are probed for deviations in magnitude from the standard model predictions in multiple ways, including searches for invisible and undetected decays. No significant deviations are found.

Jet production in PbPb collisions at a nucleon-nucleon center-of-mass energy of 2.76 TeV was studied with the Compact Muon Solenoid (CMS) detector at the LHC, using a data sample corresponding to an integrated luminosity of $6.7\phantom{\rule{0.28em}{0ex}}\ensuremath{\mu}$b${}^{\ensuremath{-}1}$. Jets are reconstructed using the energy deposited in the CMS calorimeters and studied as a function of collision centrality. With increasing collision centrality, a striking imbalance in dijet transverse momentum is observed, consistent with jet quenching. The observed effect extends from the lower cutoff used in this study (jet ${p}_{\mathrm{T}}=120$ GeV/c) up to the statistical limit of the available data sample (jet ${p}_{\mathrm{T}}\ensuremath{\approx}210$ GeV/c). Correlations of charged particle tracks with jets indicate that the momentum imbalance is accompanied by a softening of the fragmentation pattern of the second most energetic, away-side jet. The dijet momentum balance is recovered when integrating low transverse momentum particles distributed over a wide angular range relative to the direction of the away-side jet.

A bstract A detailed description is reported of the analysis used by the CMS Collaboration in the search for the standard model Higgs boson in pp collisions at the LHC, which led to the observation of a new boson. The data sample corresponds to integrated luminosities up to 5.1 fb −1 at $ \sqrt{s}=7 $ TeV, and up to 5.3 fb −1 at $ \sqrt{s}=8 $ TeV . The results for five Higgs boson decay modes γγ , ZZ, WW, ττ , and bb, which show a combined local significance of 5 standard deviations near 125 GeV, are reviewed. A fit to the invariant mass of the two high resolution channels, γγ and ZZ → 4 ℓ , gives a mass estimate of 125 . 3 ± 0 . 4 (stat.) ± 0 . 5 (syst.) GeV. The measurements are interpreted in the context of the standard model Lagrangian for the scalar Higgs field interacting with fermions and vector bosons. The measured values of the corresponding couplings are compared to the standard model predictions. The hypothesis of custodial symmetry is tested through the measurement of the ratio of the couplings to the W and Z bosons. All the results are consistent, within their uncertainties, with the expectations for a standard model Higgs boson.

Combined results are reported from searches for the standard model Higgs boson in proton-proton collisions at s = 7 TeV in five Higgs boson decay modes: , bb, , WW, and ZZ. The explored Higgs boson mass range is 110-600 GeV. The analysed data correspond to an integrated luminosity of 4.6-4.8 fb -1 . The expected excluded mass range in the absence of the standard model Higgs boson is 118-543 GeV at 95% CL. The observed results exclude the standard model Higgs boson in the mass range 127-600 GeV at 95% CL, and in the mass range 129-525 GeV at 99% CL. An excess of events above the expected standard model background is observed at the low end of the explored mass range making the observed limits weaker than expected in the absence of a signal. The largest excess, with a local significance of 3.1 , is observed for a Higgs boson mass hypothesis of 124 GeV. The global significance of observing an excess with a local significance 3.1 anywhere in the search range 110-600 (110-145) GeV is estimated to be 1.5 (2.1 ). More data are required to ascertain the origin of the observed excess.

New sets of parameters ("tunes") for the underlying-event (UE) modelling of the pythia8, pythia6 and herwig++ Monte Carlo event generators are constructed using different parton distribution functions. Combined fits to CMS UE proton-proton ([Formula: see text]) data at [Formula: see text] and to UE proton-antiproton ([Formula: see text]) data from the CDF experiment at lower [Formula: see text], are used to study the UE models and constrain their parameters, providing thereby improved predictions for proton-proton collisions at 13[Formula: see text]. In addition, it is investigated whether the values of the parameters obtained from fits to UE observables are consistent with the values determined from fitting observables sensitive to double-parton scattering processes. Finally, comparisons are presented of the UE tunes to "minimum bias" (MB) events, multijet, and Drell-Yan ([Formula: see text] lepton-antilepton+jets) observables at 7 and 8[Formula: see text], as well as predictions for MB and UE observables at 13[Formula: see text].

Agricultural and industrial practices more than doubled the intrinsic rate of terrestrial N fixation over the past century with drastic consequences, including increased atmospheric nitrous oxide (N(2)O) concentrations. N(2)O is a potent greenhouse gas and contributor to ozone layer destruction, and its release from fixed N is almost entirely controlled by microbial activities. Mitigation of N(2)O emissions to the atmosphere has been attributed exclusively to denitrifiers possessing NosZ, the enzyme system catalyzing N(2)O to N(2) reduction. We demonstrate that diverse microbial taxa possess divergent nos clusters with genes that are related yet evolutionarily distinct from the typical nos genes of denitirifers. nos clusters with atypical nosZ occur in Bacteria and Archaea that denitrify (44% of genomes), do not possess other denitrification genes (56%), or perform dissimilatory nitrate reduction to ammonium (DNRA; (31%). Experiments with the DNRA soil bacterium Anaeromyxobacter dehalogenans demonstrated that the atypical NosZ is an effective N(2)O reductase, and PCR-based surveys suggested that atypical nosZ are abundant in terrestrial environments. Bioinformatic analyses revealed that atypical nos clusters possess distinctive regulatory and functional components (e.g., Sec vs. Tat secretion pathway in typical nos), and that previous nosZ-targeted PCR primers do not capture the atypical nosZ diversity. Collectively, our results suggest that nondenitrifying populations with a broad range of metabolisms and habitats are potentially significant contributors to N(2)O consumption. Apparently, a large, previously unrecognized group of environmental nosZ has not been accounted for, and characterizing their contributions to N(2)O consumption will advance understanding of the ecological controls on N(2)O emissions and lead to refined greenhouse gas flux models.

NASA's Black Marble nighttime lights product suite (VNP46) is available at 500 m resolution since January 2012 with data from the Visible Infrared Imaging Radiometer Suite (VIIRS) Day/Night Band (DNB) onboard the Suomi National Polar-orbiting Platform (SNPP). The retrieval algorithm, developed and implemented for routine global processing at NASA's Land Science Investigator-led Processing System (SIPS), utilizes all high-quality, cloud-free, atmospheric-, terrain-, vegetation-, snow-, lunar-, and stray light-corrected radiances to estimate daily nighttime lights (NTL) and other intrinsic surface optical properties. Key algorithm enhancements include: (1) lunar irradiance modeling to resolve non-linear changes in phase and libration; (2) vector radiative transfer and lunar bidirectional surface anisotropic reflectance modeling to correct for atmospheric and BRDF effects; (3) geometric-optical and canopy radiative transfer modeling to account for seasonal variations in NTL; and (4) temporal gap-filling to reduce persistent data gaps. Extensive benchmark tests at representative spatial and temporal scales were conducted on the VNP46 time series record to characterize the uncertainties stemming from upstream data sources. Initial validation results are presented together with example case studies illustrating the scientific utility of the products. This includes an evaluation of temporal patterns of NTL dynamics associated with urbanization, socioeconomic variability, cultural characteristics, and displaced populations affected by conflict. Current and planned activities under the Group on Earth Observations (GEO) Human Planet Initiative are aimed at evaluating the products at different geographic locations and time periods representing the full range of retrieval conditions.

Concern and interest related to the effects of nanomaterials on living organisms are growing in both the scientific and public communities. Reports have described the toxicity of nanoparticles (NPs) on micro- and macro-organisms, including some plant species. Nevertheless, to the authors' knowledge there are no reports on the biotransformation of NPs by edible terrestrial plants. Here, shown for the first time, is evidence pertaining to the biotransformation of ZnO and CeO(2) NPs in plant seedlings. Although the NPs did not affect soybean germination, they produced a differential effect on plant growth and element uptake. By using synchrotron X-ray absorption spectroscopy we obtained clear evidence of the presence of CeO(2) NPs in roots, whereas ZnO NPs were not present. Random amplified polymorphic DNA assay was applied to detect DNA damage and mutations caused by NPs. Results obtained from the exposure of soybean plants to CeO(2) NPs show the appearance of four new bands at 2000 mg L(-1) and three new bands at 4000 mg L(-1) treatment. In this study we demonstrated genotoxic effects from the exposure of soybean plants to CeO(2) NPs.